A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia.
3-alpha-hydroxyacyl-CoA dehydrogenase deficiency
Hydroxyacyl-coenzyme A dehydrogenase deficiency
An autosomal recessive, metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death.
3-hydroxy-3-methylglutaryl-CoA lyase deficiency
An autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.
3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency
Mitochondrial HMG-CoA synthase deficiency
A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly.
3-hydroxyisobutryl-CoA hydrolase deficiency
Beta-hydroxyisobutyryl CoA deacylase deficiency
Deficiency of beta-hydroxyisobutyryl CoA deacylase
An autosomal recessive inborn error of valine metabolism. It causes severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia.
An autosomal recessive inborn error of isoleucine catabolism characterized by intermittent ketoacidotic attacks associated with unconsciousness. Some patients die during an attack or are mentally retarded. Urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, triglylglycine, butanone is increased. It seems likely that the severity of this disease correlates better with the environmental or acquired factors than with the ACAT1 genotype.
3-methylcrotonoyl-CoA carboxylase 1 deficiency
An autosomal recessive disorder of leucine catabolism. The phenotype is variable, ranging from neonatal onset with severe neurological involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency.
3-methylcrotonoyl-CoA carboxylase 2 deficiency
3-alpha-methylglutaconic aciduria type 1
3-alpha-methylglutaconyl-CoA hydratase deficiency
3-methylglutaconyl-CoA hydratase deficiency
An inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGCA1 can be distinguished from other forms of MGCA by the pattern of metabolite excretion: 3-methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other MGCA forms).
3-alpha-methylglutaconic aciduria type 3
An autosomal recessive metabolic disorder that causes a neuro-ophthalmologic syndrome consisting of early-onset bilateral optic atrophy, spasticity, extrapyramidal dysfunction and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid is increased. MGCA3 can be distinguished from MGCA1 by the absence of increase of 3-hydroxyisovaleric acid levels.
3-alpha-methylglutaconic aciduria type 5
An autosomal recessive disorder characterized by early-onset dilated cardiomyopathy, growth failure, cerebellar ataxia causing significant motor delays, testicular dysgenesis, growth failure and significant increases in urine organic acids, particularly 3-methylglutaconic acid and 3-methylglutaric acid.
3-methylglutaconic aciduria, type VIIA, autosomal dominant
3-methylglutaconic aciduria with neurologic involvement and neutropenia, autosomal dominant
An autosomal dominant inborn error of metabolism with a highly variable phenotype. Primary disease symptoms are increased levels of 3-methylglutaconic acid, neurologic deterioration and neutropenia. Other common features include progressive encephalopathy, movement abnormalities, delayed psychomotor development, impaired intellectual development, cataracts, seizures, and recurrent infections.
3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia
3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia
An autosomal recessive inborn error of metabolism with a highly variable phenotype. Primary disease symptoms are increased levels of 3-methylglutaconic acid, neurologic deterioration and neutropenia. Other common features include progressive encephalopathy, movement abnormalities, delayed psychomotor development,impaired intellectual development, cataracts, seizures, and recurrent infections.
An autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy.
An autosomal recessive disease characterized by early-onset seizures, severely delayed psychomotor development and intellectual disability. Patients have hypotonia or spasticity, and laboratory investigations show increased serum lactate and 3-methylglutaconic aciduria.
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
3-methylglutaconic aciduria with dystonia-deafness, hepatopathy, encephalopathy, and Leigh-like syndrome
An autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome. Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells.
An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.
A disorder characterized by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels.
A form of 3MC syndrome, an autosomal recessive disorder characterized by facial dysmorphism, craniosynostosis, learning disability, and genital, limb and vesicorenal anomalies. Facial features include hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes.
Ptosis of eyelids with diastasis recti and hip dysplasia
46,XX gonadal dysgenesis complete SRY-positive
46,XX testicular disorder of sex development
Ovotesticular disorder of sex development
A condition in which male gonads develop in a genetic female (female to male sex reversal).
46,XX sex reversal partial or complete SOX9-related
A condition in which male gonads develop in a genetic female (female to male sex reversal). Additional features in SRXX5 patients are congenital heart disease, congenital diaphragmatic hernia, and blepharophimosis-ptosis-epicanthus inversus syndrome. SRXX5 inheritance is autosomal dominant.
46,XX sex reversal with dysgenesis of kidneys, adrenals, and lungs
A disease characterized by the association of female-to-male sex reversal with dysgenesis of kidneys, adrenals, and lungs.
46,XY gonadal dysgenesis with minifascicular neuropathy
An autosomal recessive disorder characterized by gonadal dysgenesis associated with polyneuropathy. Genital anomalies include the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.
46,XY gonadal dysgenesis complete SRY-related
A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal.
A disorder of sex development. Affected individuals have a 46,XY karyotype, show gonadal dysgenesis with streak gonads, look like normal females at birth, do not develop secondary sexual characteristics at puberty and do not menstruate.
An autosomal dominant disorder of sex development. Affected individuals have a 46,XY karyotype and a genital phenotype that may range from predominantly female to predominantly male, including marked sex ambiguity. Approximately half of patients present with micropenis and bilateral or unilateral cryptorchidism, and half present with female-appearing or ambiguous external genitalia.
A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype.
46,XY sex reversal partial or complete NR5A1-related
Complete or partial 46,XY gonadal dysgenesis with or without adrenal failure
XY sex reversal with or without adrenal failure
46,XY gonadal dysgenesis complete or partial with 9p24.3 deletion
A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients display complete or partial gonadal dysgenesis and a chromosome 9p deletion.
46,XY gonadal dysgenesis complete CBX2-related
Disorder of sex development 46,XY CBX2-related
A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.
46,XY gonadal dysgenesis partial or complete MAP3K1-related
46,XY sex reversal partial or complete MAP3K1-related
46,XY gonadal dysgenesis, partial or complete, DHH-related
46,XY sex reversal, partial or complete, DHH-related
Complete pure gonadal dysgenesis 46,XY type
A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. SRXY7 patients have no functional gonads.
Male pseudohermaphroditism due to deficiency of testicular 17,20-desmolase
A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females or have ambiguous external genitalia.
Oxoprolinuria due to oxoprolinase deficiency
A disorder characterized by calcium oxalate/carbonate urolithiasis, and excessive urinary 5-oxo-L-proline. Affected individuals have recurrent episodes of vomiting, diarrhea, and abdominal pain.
A retinal disease characterized by a combination of fundus hypopigmentation, decreased visual acuity due to foveal hypoplasia, nystagmus, astigmatism, protan color vision defect, myopia, and defective dark adaptation. Except for progression of axial myopia, the disease can be considered to be a stationary condition. Electroretinography reveals abnormalities in both photopic and scotopic functions.
Faciogenital dysplasia with attention deficit-hyperactivity disorder
An X-linked recessive, rare multisystemic disorder characterized by disproportionately short stature, and by facial, skeletal and urogenital anomalies. Some patients manifest intellectual disability, attention deficit disorder and hyperactivity.
Albinism, black lock, cell migration disorder of the neurocytes of the gut and deafness
An autosomal recessive syndrome characterized by albinism, black lock at temporal occipital region, bilateral deafness, aganglionosis of the large intestine and total absence of neurocytes and nerve fibers in the small intestine.
Central obesity, type 2 diabetes, hypertension, and early-onset coronary artery disease
A form of abdominal obesity-metabolic syndrome, a disorder characterized by abdominal obesity, high triglycerides, low levels of high density lipoprotein cholesterol, high blood pressure, and elevated fasting glucose levels. AOMS3 is characterized by early-onset coronary artery disease, central obesity, hypertension, and diabetes.
A form of abdominal obesity-metabolic syndrome, a disorder characterized by abdominal obesity, high triglycerides, low levels of high density lipoprotein cholesterol, high blood pressure, and elevated fasting glucose levels. AOMS4 is an autosomal dominant disease. Patients manifest obesity, hypertension, early-onset coronary artery disease and type 2 diabetes.
Microsomal triglyceride transfer protein deficiency
An autosomal recessive disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, VLDL, LDL, lipoprotein(A)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration.
A congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth.
Abnormal hair, joint laxity, and developmental delay
An autosomal recessive disease characterized by abnormal hair, cognitive delay, speech articulation disorder, and increased joint mobility. At birth patients have normal hair that gradually becomes sparse, twisted, brittle, and easily broken, with pili torti and trichorrhexis nodosa.
A disease characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis.
A metabolic disorder characterized by a total or near total loss of catalase activity in red cells. It is often associated with ulcerating oral lesions. Acatalasemia is inherited as an autosomal recessive trait.
Aplasia cutis congenita with ectrodactyly skeletal syndrome
An autosomal dominant syndrome characterized by a highly variable phenotypic spectrum. Clinical features include aplasia cutis congenita, thin scalp hair, dry skin, dental anomalies, ectrodactyly, and skeletal and neurodevelopmental abnormalities. Craniofacial, cardiac, renal and genital anomalies have also been reported. Affected individuals have early growth deficiencies that improve with age.
An autosomal recessive disorder of iron metabolism characterized by iron accumulation in the brain as well as visceral organs. Clinical features consist of the triad of retinal degeneration, diabetes mellitus and neurological disturbances.
An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.
Achalasia-addisonianism-alacrima syndrome
ACTH-resistant adrenal insufficiency with achalasia and alacrima
Alacrima-achalasia-adrenal insufficiency neurologic disorder
An autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)-resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present.
Very rare condition characterized by bilateral congenital amputations of the hands and feet. The specific malformative phenotype consists of a complete amputation of the distal epiphysis of the humerus, amputation of the tibial diaphysis and aplasia of the radius, ulna, fibula and of all the bones of the hands and feet.
A form of achondrogenesis type 1, a lethal form of chondrodysplasia characterized by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues.
A form of achondrogenesis type 1, a lethal form of chondrodysplasia characterized by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. ACG1B is an autosomal recessive disease.
Achondrogenesis-hypochondrogenesis type II
An autosomal dominant disease characterized by the absence of ossification in the vertebral column, sacrum and pubic bones.
A frequent form of short-limb dwarfism. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. ACH is an autosomal dominant disease.
Achondroplasia, severe, with developmental delay and acanthosis nigricans
A severe form of achondroplasia associated with developmental delay and acanthosis nigricans. Patients manifest short-limb dwarfism, with a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Acanthosis nigricans is a skin condition characterized by brown-pigmented, velvety verrucosities in body folds and creases.
An autosomal recessive, ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus.
An autosomal recessive, ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. Achromatopsia type 3 patients manifest severe myopia.
An ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus.
A form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. ACHM5 inheritance is autosomal recessive.
A form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus.
A disorder characterized by severely reduced serum IGF-I and IGFBP-3 concentrations and mild growth retardation. Pubertal delay in boys and insulin insensitivity are common findings.
A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty.
Acne inversa, familial, 2, with or without Dowling-Degos disease
An autosomal dominant form of acne inversa, a chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Some ACNINV2 patients also exhibit reticulate hyperpigmentation consistent with Dowling-Degos disease.
Acro-dermato-ungual-lacrimal-tooth syndrome
A form of ectodermal dysplasia. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia and loss of permanent teeth. ADULT syndrome differs significantly from EEC3 syndrome by the absence of facial clefting. Inheritance is autosomal dominant.
Hallux duplication postaxial polydactyly and absence of corpus callosum
An autosomal recessive syndrome characterized by hypogenesis or agenesis of the corpus callosum. Clinical features include postaxial polydactyly, hallux duplication, macrocephaly, craniofacial abnormalities, severe developmental delay and intellectual disability.
An autosomal recessive disorder characterized by short stature of variable severity with postnatal onset. The most constant radiographic abnormalities are observed in the tubular bones of the hands and in the proximal part of the femur. Cone-shaped epiphyses or a similar epiphyseal configuration with premature epimetaphyseal fusion result in shortening of the skeletal components involved. Cone-shaped epiphyses are also present to a variable extent at the shoulders, knees and ankles.
Acrodermatitis enteropathica, zinc-deficiency type
A rare autosomal recessive disease caused by the inability to absorb sufficient zinc. The clinical features are growth retardation, immune-system dysfunction, alopecia, severe dermatitis, diarrhea and occasionally mental disorders.
Acrodysostosis 1, with or without hormone resistance
A form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities.
Acrodysostosis 2, with or without hormone resistance
A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.
Mandibulofacial dysostosis Treacher Collins type with limb anomalies
A form of acrofacial dysostosis, a group of disorders which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of AFD1 include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hyoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported.
A form of acrofacial dysostosis, a group of disorders which are characterized by malformation of the craniofacial skeleton and, in some patients, the limbs.
An autosomal dominant condition characterized by dysplastic nails, postaxial polydactyly, dental anomalies, short limbs, short stature and normal intelligence. The phenotype is milder than Ellis-van Creveld syndrome.
A localized disorder of keratinization, which is inherited as an autosomal dominant trait. Its onset is early in life with multiple flat-topped, flesh-colored papules on the hands and feet, punctate keratoses on the palms and soles, with varying degrees of nail involvement. The histopathology shows a distinctive pattern of epidermal features with hyperkeratosis, hypergranulosis and acanthosis together with papillomatosis. These changes are frequently associated with circumscribed elevations of the epidermis that are said to resemble church spires. There are no features of dyskeratosis or acantholysis, the typical findings in lesions of Darier disease.
A rare variant form of frontonasal dysplasia, an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism, broadening of the nasal root, median facial cleft affecting the nose and/or upper lip and palate, unilateral or bilateral clefting of the alae nasi, lack of formation of the nasal tip, anterior cranium bifidum occultum, a V-shaped or widow's peak frontal hairline. AFND is characterized by the association of frontonasal malformations with various combinations of polydactyly, tibial hypoplasia, epibulbar dermoid, encephalocoele, corpus callosum agenesis and Dandy-Walker malformation.
A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD1 is an autosomal recessive form characterized by axial skeletal involvement with wedging of vertebral bodies. All skeletal elements are present but show abnormal rates of linear growth.
Acromesomelic chondrodysplasia, Grebe type
A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD2A is an autosomal recessive form characterized by normal axial skeletons and missing or fused skeletal elements within the hands and feet.
Fibular hypoplasia and complex brachydactyly
A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD2B is an autosomal recessive form characterized by acromesomelic limb shortening with severe reduction or absence of the fibula, and severe hand and feet abnormalities including complex brachydactyly.
Acromesomelic chondrodysplasia, Hunter-Thompson type
A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD2C is an autosomal recessive form characterized by skeletal abnormalities restricted to the limbs. The craniofacial skeleton and axial skeletal structures are normal.
Acromesomelic chondrodysplasia, with genital anomalies
Chondrodysplasia, acromesomelic, with or without genital anomalies
A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD3 is an autosomal recessive form characterized by bilateral aplasia of the fibula, severe brachydactyly, and fusion of carpal and tarsal bones.
A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD4 radiographic hallmarks include mild to moderate platyspondyly, moderate brachydactyly, iliac flaring, and metaphyseal alterations of the long bones that progressively increase with age. AMD4 inheritance is autosomal recessive.
An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have distinct facial features, including round face, well-defined eyebrows, long eyelashes, bulbous nose with anteverted nostrils, long and prominent philtrum, and thick lips with a small mouth. Other characteristic features include hoarse voice and pseudomuscular build, and there are distinct skeletal features as well, including an internal notch of the femoral head, internal notch of the second metacarpal, and external notch of the fifth metacarpal.
An autosomal recessive disorder that is characterized by adrenal insufficiency symptoms, such as weight loss, lack of appetite (anorexia), weakness, nausea, vomiting and low blood pressure (hypotension). The pituitary hormone ACTH is decreased or absent, and other cortisol and other steroid hormone levels in the blood are abnormally low.
ACTH-independent macronodular adrenal hyperplasia 1
ACTH-independent macronodular adrenocortical hyperplasia
Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia
Corticotropin-independent macronodular adrenal hyperplasia
A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
ACTH-independent macronodular adrenal hyperplasia 2
Primary macronodular adrenal hyperplasia
A form of macronodular adrenal hyperplasia characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
Delta-aminolevulinate dehydratase deficiency
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.
Acyl-CoA dehydrogenase medium-chain deficiency
Carnitine deficiency secondary to medium-chain acyl-Coa dehydrogenase deficiency
An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy.
Acyl-CoA dehydrogenase short-chain deficiency
Lipid-storage myopathy secondary to short-chain acyl-CoA dehydrogenase deficiency
An inborn error of mitochondrial fatty acid beta-oxidation resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.
Acyl-CoA dehydrogenase very long-chain deficiency
Acyl-CoA dehydrogenase long-chain deficiency
An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting.
Aplasia cutis congenita with terminal transverse limb defects
Congenital scalp defects with distal limb reduction anomalies
A disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins.
An autosomal dominant form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. AOS3 patients manifest characteristic vertex scalp defects and terminal limb defects, but without congenital heart defects, other associated defects, or immune defects.
A form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins.
Adenine phosphoribosyltransferase deficiency
An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.
Adenosine monophosphate deaminase deficiency erythrocyte type
AMP deaminase deficiency erythrocyte type
A metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady-state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders.
An autosomal recessive disorder characterized by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present.
An autosomal dominant condition characterized by the lack of epidermal ridges on the palms and soles, which results in the absence of fingerprints, and is associated with a reduced number of sweat gland openings and reduced sweating of palms and soles.
A stationary, benign disorder characterized by tonic, sluggishly reacting pupil and hypoactive or absent tendon reflexes. Adie pupil is a characteristic of Charcot-Marie-Tooth disease type 2J.
A condition that results in very low concentrations of plasma adiponectin.
Congenital lipoid hyperplasia of adrenal cortex with male pseudohermaphroditism
The most severe form of adrenal hyperplasia. It is a condition characterized by onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro-opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. Affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacement are not instituted.
3-beta-hydroxysteroid dehydrogenase type II deficiency
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase type II deficiency
A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic). In AH2, virilization is much less marked or does not occur. AH2 is frequently lethal in early life.
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Hyperandrogenism nonclassic type due to 21-hydroxylase deficiency
A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic).
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency
Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency
Adrenal hypoplasia, congenital, with hypogonadotropic hypogonadism
AHC with isolated gonadotropin deficiency
A disorder of adrenal gland development characterized by absence of the permanent zone of the adrenal cortex, structural disorganization of the adrenal glands, adrenal insufficiency and profound hormonal deficiencies. AHC patients manifest primary adrenal failure usually in early infancy, and hypogonadotropic hypogonadism leading to absent or incomplete sexual maturation. AHC can be inherited in an X-linked or autosomal recessive pattern.
Adrenal insufficiency, congenital, with 46,XY sex reversal
Adrenal insufficiency congenital with 46,XY sex reversal partial or complete
A rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure. Patients with congenital adrenal insufficiency do not manifest the massive adrenal enlargement typical of congenital lipoid adrenal hyperplasia.
A disorder characterized by adrenal insufficiency, muscular hypotonia, decreased sodium and increased potassium levels, elevated ACTH, salt-wasting crisis, prolonged jaundice, hypoglycemia, and vomiting.
A malignant neoplasm of the adrenal cortex and a rare childhood tumor. It occurs with increased frequency in patients with Beckwith-Wiedemann syndrome and Li-Fraumeni syndrome.
A peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype.
A peroxisomal single-enzyme disorder of fatty acid beta-oxidation, resulting in clinical manifestations that remind neonatal adrenoleukodystrophy. Clinical features include intellectual disability, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.
Advanced sleep phase syndrome, familial, 1
An autosomal dominant disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms.
Advanced sleep phase syndrome, familial, 2
Advanced sleep phase syndrome, familial, 3
Advanced sleep phase syndrome, familial, 4
Agammaglobulinemia 1, autosomal recessive
Agammaglobulinemia autosomal recessive due to IGHM defect
A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
Agammaglobulinemia 10, autosomal dominant
Agammaglobulinemia, autosomal dominant, due to SPI1 defect
A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
Agammaglobulinemia 2, autosomal recessive
Agammaglobulinemia autosomal recessive due to IGLL1 defect
Agammaglobulinemia 3, autosomal recessive
Agammaglobulinemia autosomal recessive due to CD79A defect
A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
Agammaglobulinemia 4, autosomal recessive
Agammaglobulinemia autosomal recessive due to BLNK defect
Agammaglobulinemia 5, autosomal dominant
Agammaglobulinemia autosomal dominant due to LRRC8A defect
Agammaglobulinemia 6, autosomal recessive
Agammaglobulinemia autosomal recessive due to CD79B defect
Agammaglobulinemia 7, autosomal recessive
Agammaglobulinemia autosomal recessive due to PIK3R1 defect
Agammaglobulinemia 8A, autosomal dominant
Agammaglobulinemia, autosomal dominant, due to TCF3 defect
Agammaglobulinemia 8B, autosomal recessive
Agammaglobulinemia, autosomal recessive, due to TCF3 defect
A form of agammaglobulinemia, a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. AGM8B is characterized by onset of recurrent infections in early childhood. AGM8B patients may show dysmorphic facies and subtle abnormalities of other immune cells, such as T cells.
Agammaglobulinemia 9, autosomal recessive
Agammaglobulinemia, autosomal recessive, due to SLC39A7 defect
Agenesis of corpus callosum, cardiac, ocular, and genital syndrome
An autosomal dominant, syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, mirror movements, dysmorphic features, and ocular, cardiac, and genital anomalies.
Agenesis of the corpus callosum, with abnormal genitalia
Corpus callosum, agenesis of, with abnormal genitalia
Micrencephaly-corpus callosum agenesis-abnormal genitalia
An X-linked syndrome with variable expression in females. It is characterized by agenesis of corpus callosum, intellectual disability and seizures. Manifestations in surviving males include severe acquired micrencephaly, intellectual disability, limb contractures, scoliosis, tapered fingers with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophrys, optic atrophy, broad alveolar ridges, and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias.
Agenesis of the corpus callosum, with facial anomalies and cerebellar ataxia
Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia
An autosomal recessive intellectual disability syndrome characterized by congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment.
Agenesis of the corpus callosum, with peripheral neuropathy
Corpus callosum, agenesis of, with neuronopathy
Polyneuropathy, sensorimotor, with or without agenesis of the corpus callosum
A disease that is characterized by severe progressive sensorimotor neuropathy, intellectual disability, dysmorphic features and complete or partial agenesis of the corpus callosum.
Agenesis of the corpus callosum, X-linked, partial
A syndrome characterized by partial corpus callosum agenesis, hypoplasia of inferior vermis and cerebellum, intellectual disability, seizures and spasticity. Other features include microcephaly, unusual facies, and Hirschsprung disease in some patients.
Dysgnathia complex agnathia-holoprosencephaly
A rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal.
AICAR transformylase/IMP cyclohydrolase deficiency
A neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. Clinical features include profound intellectual disability, epilepsy, dysmorphic features and congenital blindness. AICAR inheritance is autosomal recessive.
Autosomal dominant Aicardi-Goutieres syndrome
Encephalopathy familial infantile with intracranial calcification and chronic cerebrospinal fluid lymphocytosis
A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.
A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. AGS8 inheritance is autosomal recessive.
Growth retardation, spine malformation, dysmorphic facies, and developmental delay
An autosomal recessive developmental disorder characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delay.
A severe disorder characterized by prenatal growth retardation, large joints contractures, camptodactyly, bilateral talipes equinovarus, small mouth, anterior segment anomalies of the eyes, and early lethality. The transmission pattern of the disorder is consistent with autosomal recessive inheritance.
Macrocephaly with multiple epiphyseal dysplasia and distinctive facies
An autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance.
A syndrome characterized by delayed psychomotor development, moderate to severe intellectual disability, poor or absent speech, microcephaly, congenital hypotonia, and severe growth delay.
Alacrima, achalasia, and impaired intellectual development syndrome
An autosomal recessive disorder characterized by onset of alacrima, achalasia, and intellectual disability at birth or in early infancy. More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency.
Cholestasis with peripheral pulmonary stenosis
A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems.
Facial dysmorphism intellectual disability and primordial dwarfism
A syndromic form of primordial dwarfism, a condition characterized by severe growth restriction that has its onset in utero, and results in short stature and undersize. ALAZS patients manifest severe intellectual disability and distinct facial features including malar hypoplasia, deep-set eyes, broad nose, short philtrum, and macrostomia. Some patients have non-specific and inconsistent skeletal findings, for example, scoliosis and mild epiphyseal changes in the proximal phalanges, but no frank dysplasia.
An autosomal recessive syndrome reminiscent of Cornelia de Lange syndrome and characterized by delayed psychomotor development with intellectual disability, hypotonia, microcephaly, short stature, poor speech, and dysmorphic features.
Form of albinism affecting only the eye. Pigment of the hair and skin is normal or only slightly diluted. Eyes may be severely affected with photophobia and reduced visual acuity. Nystagmus or strabismus are often associated. The irides and fundus are depigmented.
Oculocutaneous albinism tyrosinase negative
An autosomal recessive disorder in which the biosynthesis of melanin pigment is absent in skin, hair, and eyes. It is characterized by complete lack of tyrosinase activity due to production of an inactive enzyme. Patients present with a life-long absence of melanin pigment after birth, and manifest increased sensitivity to ultraviolet radiation with predisposition to skin cancer. Visual anomalies include decreased acuity, nystagmus, strabismus and photophobia.
Oculocutaneous albinism type I temperature-sensitive
An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. It is characterized by partial lack of tyrosinase activity. Patients have white hair at birth that rapidly turns yellow or blond. They manifest the development of minimal-to-moderate amounts of cutaneous and ocular pigment. Some patients may have with white hair in the warmer areas (scalp and axilla) and progressively darker hair in the cooler areas (extremities). This variant phenotype is due to a loss of tyrosinase activity above 35-37 degrees C.
Oculocutaneous albinism tyrosinase-positive
An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Although affected infants may appear at birth to have complete absence of melanin pigment, most patients acquire small amounts of pigment with age. Visual anomalies include decreased acuity and nystagmus. The phenotype is highly variable. The hair of affected individuals may turn darker with age, and pigmented nevi or freckles may be seen. African and African American individuals may have yellow hair and blue-gray or hazel irides. One phenotypic variant, 'brown OCA,' has been described in African and African American populations and is characterized by light brown hair and skin color and gray to tan irides.
An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Tyrosinase activity is normal and patients have only moderate reduction of pigment. The eyes present red reflex on transillumination of the iris, dilution of color of iris, nystagmus and strabismus. Darker-skinned individuals have bright copper-red coloration of the skin and hair.
A disorder of pigmentation characterized by reduced biosynthesis of melanin in the skin, hair and eyes. Patients show reduced or lacking pigmentation associated with classic albinism ocular abnormalities, including decreased visual acuity, macular hypoplasia, optic dysplasia, atypical choroidal vessels, and nystagmus.
A disorder characterized by a reduction or complete loss of melanin in the skin, hair and eyes. Patients show reduced or lacking pigmentation often accompanied by eye symptoms such as photophobia, strabismus, moderate to severe visual impairment, and nystagmus.
A form of oculocutaneous albinism, a disorder of pigmentation characterized by reduced biosynthesis of melanin in the skin, hair and eyes. OCA8 is an autosomal recessive form characterized by mild hair and skin hypopigmentation, associated with ocular features including nystagmus, reduced visual acuity, iris transillumination, and hypopigmentation of the retina.
A disorder characterized by short stature, obesity, round facies, brachydactyly and subcutaneous calcification. It is often associated with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels.
A rare disorder of the central nervous system. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death within the first decade. Infants with Alexander disease develop a leukodystrophy with macrocephaly, seizures, and psychomotor retardation. Patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. Histologically, Alexander disease is characterized by Rosenthal fibers, homogeneous eosinophilic inclusions in astrocytes.
An autosomal recessive error of metabolism characterized by an increase in the level of homogentisic acid. The clinical manifestations are urine that turns dark on standing and alkalinization, black ochronotic pigmentation of cartilage and collagenous tissues, and spine arthritis.
An autosomal recessive syndrome characterized by brain atrophy and arthrogryposis. Patients present with cerebral parenchymal underdevelopment, lissencephaly, severe to mild ventriculomegaly, and cerebellar hypoplasia with brainstem dysgenesis. Most affected individuals die in utero or soon after birth. The few patients who survive have variable intellectual disability and may have seizures. Facial dysmorphism, cardiac and ophthalmologic anomalies, such as microphthalmia and cataract, are additional features.
A common disease with complex inheritance characterized by mucosal inflammation caused by allergen exposure.
A rare disorder characterized by loss of hair from the entire body. No hair are present in hair follicles on skin biopsy.
Alopecia, neurologic defects, and endocrinopathy syndrome
Alopecia-progressive neurological defect-endocrinopathy
Affected individuals have hair loss of variable severity, ranging from complete alopecia to near-normal scalp hair with absence of body hair. All have moderate to severe intellectual disability, progressive motor deterioration and central hypogonadotropic hypogonadism with delayed or absent puberty and central adrenal insufficiency. Additional features included short stature, microcephaly, gynecomastia, pigmentary anomalies, hypodontia, kyphoscoliosis, ulnar deviation of the hands, and loss of subcutaneous fat.
Alopecia-intellectual disability syndrome 1
Alopecia with severe intellectual deficit
A rare autosomal recessive form of alopecia. APMR1 patients show loss of hair on the scalp, absence of eyebrows, eyelashes, axillary and pubic hair, and mild to severe intellectual disability.
Alopecia-intellectual disability syndrome 4
An autosomal recessive disorder characterized by alopecia universalis, scaly skin, mild to severe intellectual disability, delayed or absent speech, and motor delay.
A disorder whose most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age.
An autosomal recessive disorder resulting in severe hemorrhagic diathesis.
Alpha-aminoadipic and alpha-ketoadipic aciduria
An autosomal recessive metabolic disorder characterized by increased levels of 2-oxoadipate and 2-hydroxyadipate in the urine, and elevated 2-aminoadipate in the plasma. Patients can have mild to severe intellectual disability, muscular hypotonia, developmental delay, ataxia, and epilepsy. Most cases are asymptomatic.
A benign condition characterized by undetectable AFP levels in the amniotic fluid. Affected individuals are asymptomatic and present normal development.
Alpha-fetoprotein, hereditary persistence
A benign autosomal dominant condition characterized by continued expression of alpha-fetoprotein in adult life.
Alpha-methylacyl-CoA racemase deficiency
A rare autosomal recessive peroxisomal disorder characterized by elevated plasma concentrations of pristanic acid C27-bile-acid intermediates, and adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging.
A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia).
Alpha-thalassemia myelodysplasia syndrome
Acquired alpha-thalassemia with myelodysplastic syndrome
A disorder characterized by hypochromic, microcytic red blood cells, hemoglobin H detected in peripheral blood, and multilineage myelodysplasia.
Alpha-thalassemia/impaired intellectual development syndrome, X-linked
A disorder characterized by severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.
Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunity
An immunological disorder characterized by oligoclonal expansion of TCR gamma/delta T-cells, TCR alpha/beta T-cell lymphopenia, severe, disseminated cytomegalovirus infection and autoimmune cytopenia.
A syndrome that is characterized by progressive glomerulonephritis, renal failure, sensorineural deafness, specific eye abnormalities (lenticonous and macular flecks), and glomerular basement membrane defects. The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
A rare autosomal recessive disorder characterized by progressive cone-rod retinal dystrophy, neurosensory hearing loss, early childhood obesity and diabetes mellitus type 2. Dilated cardiomyopathy, acanthosis nigricans, male hypogonadism, hypothyroidism, developmental delay and hepatic dysfunction can also be associated with the syndrome.
A rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment. It is typically distinguished from familial hemiplegic migraine by infantile onset and high prevalence of associated neurological deficits that become increasingly obvious with age.
Alveolar capillary dysplasia with misalignment of pulmonary veins
Alveolar capillary dysplasia with misalignment of pulmonary veins and other congenital anomalies
A rare developmental disorder characterized by abnormal development of the capillary vascular system in the lungs. Histological features include failure of formation and ingrowth of alveolar capillaries, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. Affected infants present with respiratory distress and the disease is fatal within the newborn period. Additional features include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs. ACDMPV is a rare cause of persistent pulmonary hypertension of the newborn, an abnormal physiologic state caused by failure of transition of the pulmonary circulation from the high pulmonary vascular resistance of the fetus to the low pulmonary vascular resistance of the newborn.
Neurodevelopmental disorder with dysmorphic facies and cataracts
An autosomal recessive disorder characterized by severe global developmental delay, impaired intellectual function, poor or absent speech, microcephaly, and facial dysmorphism. Additional variable features include early-onset cataracts, hypotonia, lower limb spasticity, and congenital heart malformations.
Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Early-onset Alzheimer disease with cerebral amyloid angiopathy
A form of Alzheimer disease, a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. It can be associated with cerebral amyloid angiopathy. Alzheimer disease can be associated with cerebral amyloid angiopathy.
A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Early-onset familial Alzheimer disease 3
Familial Alzheimer disease 3 with spastic paraparesis and apraxia
Familial Alzheimer disease 3 with spastic paraparesis and unusual plaques
A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
A familial, late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. AMEDS is an autosomal recessive, digenic form characterized by childhood onset of bone marrow failure resulting in aplastic anemia, in association with global developmental delay, intellectual disability, and poor overall growth with short stature.
Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome
An autosomal recessive, lethal embryonic syndrome characterized by absent hindlimbs, pulmonary hypoplasia, severely hypoplastic or absent pelvic bones, hypoplasia of the sacrum, and ambiguous genitalia.
Amelogenesis imperfecta, hypoplastic type IA
A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration.
Amelogenesis imperfecta hypoplastic local autosomal dominant
An autosomal dominant defect of enamel formation. Clinical manifestations may be variable. Some cases present with generalized enamel hypoplasia resulting in small, smooth, yellow and widely spaced teeth (smooth hypoplastic AI). Others show horizontal rows of pits, grooves or a hypoplastic area in the enamel (local hypoplastic AI).
Amelogenesis imperfecta hypoplastic with or without openbite malocclusion autosomal recessive
Amelogenesis imperfecta local hypoplastic type autosomal recessive
An autosomal recessive defect of dental enamel formation. Teeth show local hypoplastic and unmineralized enamel, and a yellow-brown discoloration. Enamel defects can be associated with facial and oral features including vertical dysgnathia and anterior openbite malocclusion.
Amelogenesis imperfecta, hypoplastic/hypomaturation type 1E
Amelogenesis imperfecta hypomaturation type with snow-capped teeth
Amelogenesis imperfecta hypoplastic/hypomaturation X-linked 1
An X-linked defect of dental enamel formation. Teeth have only a thin layer of enamel with normal hardness. The thinness of the enamel makes the teeth appear small.
Amelogenesis imperfecta, hypoplastic type IF
A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. AI1F is characterized by hypoplastic enamel of the primary and secondary dentition.
Amelogenesis imperfecta and gingival fibromatosis syndrome
Hypoplastic amelogenesis imperfecta with nephrocalcinosis
A disorder characterized by dental anomalies, gingival overgrowth, and nephrocalcinosis. Dental anomalies include hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay of tooth eruption, hypodontia/oligodontia, pericoronal radiolucencies and unerupted teeth.
A disorder characterized by defective enamel formation, resulting in hypoplastic and hypomineralized tooth enamel that may be rough, pitted, and/or discolored.
A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. AI1J is an autosomal recessive form characterized by hypoplastic enamel, enamel discolorization ranging from yellow to black, and normal dentin.
Amelogenesis imperfecta, hypoplastic type IK
A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. AI1K is an autosomal dominant form characterized by hypoplastic enamel in all teeth.
Amelogenesis imperfecta hypocalcification type autosomal dominant
Amelogenesis imperfecta hypomineralization type
An autosomal dominant hypomineralized form of amelogenesis imperfecta, a defect of enamel formation. AI3A is characterized by enamel of normal thickness but soft and with cheesy consistency. Enamel is lost from tooth soon after eruption.
An autosomal dominant form of amelogenesis imperfecta, a defect of enamel formation. AI3B is characterized by hypomineralized enamel that has reduced tickness and exhibits structural defects.
Amelogenesis imperfecta, hypocalcification type, autosomal recessive
An autosomal recessive form of amelogenesis imperfecta, a defect of enamel formation. AI3C is characterized by generalized enamel hypocalcification affecting primary and secondary dentition. The surface of the enamel is rough and often stained. After eruption, the occlusal enamel on the molars disappears due to attrition, leaving a ring of intact enamel remaining on the sides.
Amelogenesis imperfecta 2 hypocalcification type
Amelogenesis imperfecta hypomaturation-hypoplastic type with taurodontism
Amelogenesis imperfecta with taurodontism
An autosomal dominant defect of enamel formation associated with enlarged pulp chambers. Enamel is thin, teeth are small and widely spaced.
Amelogenesis imperfecta, hypomaturation type, 2A1
Amelogenesis imperfecta pigmented hypomaturation type 1
A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel.
Amelogenesis imperfecta, hypomaturation type, 2A2
Amelogenesis imperfecta pigmented hypomaturation type 2
Amelogenesis imperfecta, hypomaturation type, 2A3
Amelogenesis imperfecta hypomaturation type IIA3
Amelogenesis imperfecta, hypomaturation type, 2A4
Amelogenesis imperfecta pigmented hypomaturation type IIA4
Amelogenesis imperfecta, hypomaturation type, 2A5
Amelogenesis imperfecta, hypomaturation type, 2A6
Amelogenesis imperfecta, hypomaturation type, IIA6
Encephalopathy associated with aminoacylase 1 deficiency
An enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.
Alport syndrome with intellectual disability, midface hypoplasia and elliptocytosis
An X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, sensorineural hearing loss, intellectual disability, midface hypoplasia and elliptocytosis.
Amyloid cranial neuropathy with lattice corneal dystrophy
A hereditary generalized amyloidosis due to gelsolin amyloid deposition. It is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure.
Cerebral amyloid angiopathy CST3-related
Cerebroarterial amyloidosis Icelandic type
Hereditary cerebral hemorrhage with amyloidosis
Hereditary cerebral hemorrhage with amyloidosis Icelandic type
Hereditary cystatin C amyloid angiopathy
A hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low.
A form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system.
Amyloidosis, primary localized cutaneous, 1
A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins.
Amyloidosis, primary localized cutaneous, 2
Amyloidosis, primary localized cutaneous, 3
A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. PLCA3 inheritance is autosomal recessive.
Hereditary amyloidosis transthyretin-related
A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor.
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Amyotrophic lateral sclerosis 10 with or without frontotemporal dementia and with TDP43 inclusions
Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS12 inheritance can be autosomal dominant or autosomal recessive. There is also sporadic occurrence. ALS12 patients may develop frontotemporal dementia.
Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia.
Amyotrophic lateral sclerosis 16, juvenile
Amyotrophic lateral sclerosis juvenile 2
Distal myopathy with vocal cord weakness
Vocal cord and pharyngeal dysfunction with distal myopathy
A neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia.
Amyotrophic lateral sclerosis 22, with or without frontotemporal dementia
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS22 may develop frontotemporal dementia.
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS23 is an autosomal dominant form with incomplete penetrance.
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS25 is an autosomal dominant form with variable adult onset and incomplete penetrance.
Amyotrophic lateral sclerosis 26, with or without frontotemporal dementia
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS26 inheritance is autosomal dominant. Some patients may develop frontotemporal dementia.
Amyotrophic lateral sclerosis juvenile 4
Neuronopathy distal hereditary motor with pyramidal features
A form of amyotrophic lateral sclerosis with childhood- or adolescent-onset, and characterized by slow disease progression and the sparing of bulbar and respiratory muscles. Amyotrophic lateral sclerosis is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Amyotrophic lateral sclerosis 5, juvenile
A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS5 is an autosomal recessive, juvenile form characterized by onset of upper and lower motor neuron signs before age 25.
Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia
Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1
Amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam
A neurodegenerative disorder characterized by chronic, progressive and uniformly fatal amyotrophic lateral sclerosis and parkinsonism-dementia. Both diseases are known to occur in the same kindred, the same sibship and even the same individual.
A rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. Affected individuals manifest mild edema, hypotension, fatigue, and, occasionally, lower body lipodystrophy (mainly in adult females). The most common biochemical finding is hyperlipidemia, with a significant increase in the total and LDL cholesterol concentrations, but normal concentrations of HDL cholesterol and triglycerides.
An autosomal recessive spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability.
An autosomal recessive skeletal dysplasia characterized by severe short stature, brachydactyly, skin laxity, joint hypermobility and dislocations, short metacarpals, broad middle phalanges, and metaphyseal irregularities. Most patients also exhibit motor and cognitive delays.
Complete androgen insensitivity syndrome
An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.
Androgen insensitivity partial with or without breast cancer
Familial incomplete male pseudohermaphroditism, type 1
A disorder that is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.
Anemia without thrombocytopenia, X-linked
Anemia X-linked with variable neutropenia
A form of anemia characterized by abnormal morphology of erythrocytes and granulocytes in peripheral blood, bone marrow dysplasia with hypocellularity of erythroid and granulocytic lineages, and normal or increased number of megakaryocytes. Neutropenia of a variable degree is present in affected individuals.
Anemia, congenital dyserythropoietic, 1A
Congenital dyserythropoietic anemia type I
Congenital dyserythropoietic anemia type Ia
An autosomal recessive blood disorder characterized by morphological abnormalities of erythroblasts, ineffective erythropoiesis, macrocytic anemia and secondary hemochromatosis. It is occasionally associated with bone abnormalities, especially of the hands and feet (acrodysostosis), nail hypoplasia, and scoliosis. Ultrastructural features include internuclear chromatin bridges connecting some nearly completely separated erythroblasts and an abnormal appearance (spongy or Swiss-cheese appearance) of the heterochromatin in a high proportion of the erythroblasts.
Anemia, congenital dyserythropoietic, 1B
Congenital dyserythropoietic anemia type Ib
Congenital dyserythropoietic anemia type II
Hereditary erythroblastic multinuclearity with positive acidified-serum test
An autosomal recessive blood disorder characterized by morphological abnormalities of erythroblasts, ineffective erythropoiesis, normocytic anemia, iron overload, jaundice, and variable splenomegaly. Ultrastructural features include bi- or multinucleated erythroblasts in bone marrow, karyorrhexis, and the presence of Gaucher-like bone marrow histiocytes. The main biochemical feature of the disease is defective glycosylation of some red blood cells membrane proteins.
Anemia, congenital dyserythropoietic, 3A
Anemia, congenital dyserythropoietic, type III
Anemia, congenital dyserythropoietic, type IIIA
Anemia with multinucleated erythroblasts erythroreticulosis, hereditary benign
Dyserythropoietic anemia, congenital, type IIIA
An autosomal dominant blood disorder characterized by ineffective erythropoiesis, hemolytic anemia, macrocytosis in the peripheral blood, intravascular hemolysis, and giant multinucleated erythroblasts in the bone marrow.
Anemia, congenital dyserythropoietic, 3B, autosomal recessive
An autosomal recessive blood disorder characterized by marked dyserythropoiesis, hemolytic anemia, macrocytosis in the peripheral blood, and giant multinucleated erythroblasts in the bone marrow.
Congenital dyserythropoietic anemia type IV
A blood disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDA4 also have increased levels of fetal hemoglobin.
Anemia, hypochromic microcytic, with iron overload 1
A hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size. The disorder is due to an error of iron metabolism that results in high serum iron, massive hepatic iron deposition, and absence of sideroblasts and stainable bone marrow iron store. Despite adequate transferrin-iron complex, delivery of iron to the erythroid bone marrow is apparently insufficient for the demands of hemoglobin synthesis.
Anemia, hypochromic microcytic, with iron overload 2
A hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size, severe anemia, erythropoietic hyperplasia of bone marrow, massive hepatic iron deposition, and hepatosplenomegaly.
Anemia, non-spherocytic hemolytic, due to G6PD deficiency
A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life.
A form of sideroblastic anemia that shows a variable hematologic response to pharmacologic doses of pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus.
Anemia, sideroblastic, 2, pyridoxine-refractory
Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive
A form of sideroblastic anemia not responsive to pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus.
Anemia, sideroblastic, 3, pyridoxine-refractory
A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA3 is refractory to treatment with vitamin B6, while iron chelation therapy may result in clinical improvement. SIDBA3 inheritance is autosomal recessive.
A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA4 has been reported to be inherited as an autosomal recessive disease, with a pseudodominant pattern of inheritance in some families.
A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA5 inheritance is autosomal recessive.
Anemia, sideroblastic, spinocerebellar ataxia
An X-linked recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia, with hypochromia and microcytosis.
An extreme form of neural tube defect resulting in the absence of brain tissues, and death in utero or perinatally. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed. ANPH1 inheritance is autosomal recessive.
A form of anencephaly, an extreme neural tube defect resulting in the absence of brain tissues, and death in utero or perinatally. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed. ANPH2 features may also include frontonasal dysplasia with midline cleft of the upper lip and alveolar ridge, bifid nose, and clinical anophthalmia. ANPH2 inheritance is autosomal recessive.
A form of cerebral aneurysm, a focal abnormal dilatation of a blood vessel in the brain. Berry intracranial aneurysms, also known as saccular aneurysms, have a characteristic rounded shape and account for the vast majority of intracranial aneurysms. They are the most common cause of non-traumatic subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage.
A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue.
A potentially life-threatening side effect of ACE inhibitors that appears in a subset of patients taking these drugs for hypertension and cardiovascular disease treatment. AEACEI is characterized by swelling of the face, lips, tongue, and airway that can lead to suffocation and death if severe.
An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional.
Angioneurotic edema hereditary with normal C1 inhibitor concentration and function
HAE with normal C1 inhibitor concentration and function
Hereditary angioedema with normal C1 inhibitor activity
A hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives).
A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE4 is an autosomal dominant form with incomplete penetrance, variable expressivity, and female predominance.
A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE5 is an autosomal dominant form characterized by onset of episodic swelling of the face, lips, hands, and abdomen in the second decade of life.
A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE6 is an autosomal dominant form with onset in adulthood.
A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE7 is an autosomal dominant form characterized by onset of recurrent swelling of the face, lips, and oral mucosa in the second decade.
A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE8 inheritance is autosomal dominant.
A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis.
A condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions.
Anhidrosis, isolated, with normal sweat glands
Anhidrosis, familial generalized, with normal sweat glands
An autosomal recessive disorder characterized by generalized, isolated anhidrosis, severe heat intolerance, and morphologically normal eccrine sweat glands. Body growth, teeth, hair, nails, and skin are normal.
A congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.
A form of aniridia, a congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.
Ankyloblepharon-ectodermal defects-cleft lip/palate
Ankyloblepharon-ectodermal defect-cleft lip/palate
An autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.
An eating disorder characterized by the lack or loss of appetite, excess fear of becoming overweight, body image disturbance, significant weight loss, refusal to maintain minimal normal weight, and amenorrhea.
Anterior segment anomalies with or without cataract
A disease characterized by various types of developmental eye anomalies, in the absence of other abnormalities. The phenotypic spectrum of anterior segment anomalies include central corneal opacity, Peters anomaly, and bilateral persistence of the pupillary membrane. Some patients have cataract.
Familial ocular anterior segment mesenchymal dysgenesis
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis.
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. Some ASGD2 patients show congenital primary aphakia, a defect caused by eye development arrest around the 4th-5th week of gestation. This prevents the formation of any lens structure and leads to severe secondary ocular anomalies, including a complete aplasia of the anterior segment of the eye. In contrast, in secondary aphakic eyes, lens induction has occurred, and the lens vesicle has developed to some degree but finally has progressively resorbed perinatally, leading, therefore, to less severe ocular defects. ASGD2 inheritance is autosomal recessive.
Iridogoniodysgenesis anomaly, autosomal dominant
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD3 inheritance is autosomal dominant.
Iris hypoplasia with early-onset glaucoma, autosomal dominant
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD4 is an autosomal dominant disease.
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD6 patients predominantly manifest Peters anomaly. Peters anomaly consists of corneal leukoma, defects in the posterior structures of the cornea such as absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iridocorneal and/or keratolenticular adhesions. Over 50% of patients develop glaucoma in childhood.
Corneal opacification with other ocular anomalies
Sclerocornea with other ocular anomalies
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD7 is an autosomal recessive disease.
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD8 patients predominantly manifest iris and lens abnormalities, in the absence of retinal abnormalities or extra-ocular features. ASGD8 transmission pattern is consistent with autosomal recessive inheritance.
Thrombophilia due to antithrombin-III deficiency
An important risk factor for hereditary thrombophilia, a hemostatic disorder characterized by a tendency to recurrent thrombosis. Antithrombin-III deficiency is classified into 4 types. Type I: characterized by a 50% decrease in antigenic and functional levels. Type II: has defects affecting the thrombin-binding domain. Type III: alteration of the heparin-binding domain. Plasma AT-III antigen levels are normal in type II and III. Type IV: consists of miscellaneous group of unclassifiable mutations.
Antley-Bixler syndrome, with genital anomalies and disordered steroidogenesis
Antley-Bixler syndrome-like phenotype with disordered steroidogenesis
Cytochrome P450 oxidoreductase deficiency
A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures.
Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis
Multisynostotic osteodysgenesis with long bone fractures
Osteodysgenesis multisynostotic with fractures
A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.
A common multifactorial disorder characterized by permanent dilation of the abdominal aorta, usually due to degenerative changes in the aortic wall. Histologically, AAA is characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells.
Aortic aneurysm, thoracic, with or without aortic dissection
A form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
A form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. AAT12 is an autosomal dominant disease manifesting with aortic dissection and progressive dilation of the aortic root, ascending aorta, and abdominal aorta.
Aortic aneurysm/aortic dissection and patent ductus arteriosus
Non-syndromic thoracic aortic aneurysms and dissection
Thoracic aortic aneurysms and dissection
A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
Familial thoracic aortic aneurysm with livedo reticularis and iris flocculi
Aortic dissection familial with or without aortic aneurysm
A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.
A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. AOVD3 features are bicuspid aortic valve, aortic valve stenosis, and ascending aortic aneurysm. Some patients have atrial septal defects. AOVD3 inheritance is autosomal dominant with incomplete penetrance.
A syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.
A disorder characterized by congenital absence of a portion of skin in a localized or widespread area of the body. The lesions are most commonly localized on the scalp, however aplasia cutis congenita can affect any part of the body.
A rare condition characterized by dry conjunctival mucosae, irritable eyes, epiphora (constant tearing), and xerostomia (dryness of the mouth), which increases risk of dental erosion, dental caries, periodontal disease, and oral infections. ALSG has variable expressivity, and affected individuals may have aplasia or hypoplasia of the lacrimal, parotid, submandibular, and sublingual glands and absence of the lacrimal puncta.
Aplasia or hypoplasia of the breasts and/or nipples 2
A group of congenital deformities encompassing total absence of breasts and nipple (amastia), absence of the nipple (athelia), and absence of the mammary gland (amazia).
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia.
Cortisol 11-beta-ketoreductase deficiency
An autosomal recessive form of low-renin hypertension. It is usually diagnosed within the first years of life and is characterized by polyuria and polydipsia, failure to thrive, hypernatremia, severe hypertension with low renin and aldosterone levels, profound hypokalemia with metabolic alkalosis, and most often nephrocalcinosis.
An autosomal dominant disorder characterized by intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech.
A rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, intellectual disability, hypotonia, ataxia and progressive spastic quadriplegia.
An autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness.
Pseudohermaphroditism female due to placental aromatase deficiency
A rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.
Familial gynecomastia due to increased aromatase activity
An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females.
Aromatic L-amino-acid decarboxylase deficiency
Aromatic-L-amino-acid decarboxylase deficiency
An inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. It causes developmental and psychomotor delay, poor feeding, lethargy, ptosis, intermittent hypothermia, gastrointestinal disturbances. The onset is early in infancy and inheritance is autosomal recessive.
Arrhythmogenic right ventricular dysplasia 11, familial, and mild palmoplantar keratoderma and woolly hair
Arrhythmogenic right ventricular dysplasia 11 with mild palmoplantar keratoderma and woolly hair
ARVD and mild palmoplantar keratoderma with or without woolly hair
An autosomal recessive disease characterized by arrhythmogenic cardiomyopathy in association with palmoplantar keratoderma and woolly hair.
Arrhythmogenic right ventricular dysplasia, familial, 1
Arrhythmogenic right ventricular cardiomyopathy 1
Cardiomyopathy right ventricular dilated
A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias.
Arrhythmogenic right ventricular dysplasia, familial, 10
Arrhythmogenic right ventricular cardiomyopathy 10
Arrhythmogenic right ventricular dysplasia, familial, 11
Arrhythmogenic right ventricular cardiomyopathy 11
Arrhythmogenic right ventricular dysplasia, familial, 12
Arrhythmogenic right ventricular cardiomyopathy 12
Arrhythmogenic right ventricular dysplasia, familial, 13
Arrhythmogenic right ventricular cardiomyopathy 13
Arrhythmogenic right ventricular dysplasia, familial, 14
Arrhythmogenic right ventricular dysplasia, familial, 2
Arrhythmogenic right ventricular cardiomyopathy 2
Arrhythmogenic right ventricular dysplasia, familial, 5
Arrhythmogenic right ventricular cardiomyopathy 5
Arrhythmogenic right ventricular dysplasia, familial, 8
Arrhythmogenic right ventricular cardiomyopathy 8
Arrhythmogenic right ventricular dysplasia, familial, 9
Arrhythmogenic right ventricular cardiomyopathy 9
Arterial calcification of infancy, generalized, 1
Generalized arterial calcification of infancy
Idiopathic infantile arterial calcification
A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure.
Arterial calcification of infancy, generalized, 2
An autosomal recessive disorder characterized by tortuosity and elongation of major arteries, often resulting in death at young age. Other typical features include aneurysms of large arteries and stenosis of the pulmonary artery, in association with facial features and several connective tissue manifestations such as soft skin and joint laxity. Histopathological findings include fragmentation of elastic fibers in the tunica media of large arteries.
Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect
Arthrogryposis multiplex congenita, neurogenic, with myelin defect
A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC1 is an autosomal recessive severe form with onset in utero. Most affected individuals die in utero. Those who survive have generalized contractures and hypotonia. The disorder is caused by a neurogenic defect and poor or absent myelin formation around peripheral nerves rather than by a muscular defect.
Arthrogryposis multiplex congenita 2, neurogenic type
Arthrogryposis multiplex congenita, neurogenic type
A form of arthrogryposis multiplex congenita, a heterogeneous group of disorders characterized by multiple joint contractures resulting, in some cases, from reduced or absent fetal movements. AMC2 is due to a neurogenic defect and is characterized by congenital immobility of the limbs with fixation of multiple joints, and muscle wasting. AMC2 transmission pattern is consistent with autosomal recessive inheritance in several families. Penetrance may be incomplete in females.
Arthrogryposis multiplex congenita 3, myogenic type
Arthrogryposis multiplex congenita, myogenic type
A form of arthrogryposis multiplex congenita, a heterogeneous group of disorders characterized by multiple joint contractures resulting, in some cases, from reduced or absent fetal movements. AMC3 is an autosomal recessive form characterized by decreased fetal movements, muscular hypotonia, delayed motor development, loss of ambulation, variable skeletal defects, and persistent contractures of interphalangeal joints.
Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum
Arthrogryposis multiplex congenita, neurogenic, with agenesis of the corpus callosum
A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC4 is an autosomal recessive, severe form with onset in utero. Patients manifest little or no fetal movements, significant contractures affecting the upper and lower limbs, dysmorphic facial features, optic atrophy, limb fractures, profound global developmental delay, seizures, and peripheral neuropathy. Many patients die in early childhood.
A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC5 is an autosomal recessive form characterized by severe congenital contractures, developmental delay, strabismus and tremor.
A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC6 is an autosomal recessive lethal form. Death usually occurs in utero or in infancy.
Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development
An autosomal dominant disease characterized by moderate to severe intellectual disability, craniosynostosis, cleft palate, micrognathia, arthrogryposis, and short stature. Some patients may present bone abnormalities and generalized seizures.
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA11 is an autosomal dominant form characterized mainly by camptodactyly. Other features include absent flexion creases and limited forearm supination.
Arthrogryposis multiplex congenita distal type 1
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 1 is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected.
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA1C patients show multiple congenital contractures, scoliosis, short stature, and segmental amyoplasia. DA1C inheritance can be autosomal recessive or autosomal dominant.
Whistling face-windmill vane hand syndrome
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2A is characterized by contractures of the hands and feet, oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice, puckered lips, and a H-shaped dimple of the chin.
Arthrogryposis multiplex congenita distal type 2B
Arthrogryposis multiplex congenita distal type II with craniofacial abnormalities
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2B is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. DA2B1 inheritance is autosomal dominant.
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 2 is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. DA2B2 inheritance is autosomal dominant.
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 2 is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. DA2B3 inheritance is autosomal dominant.
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 2 is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures.
Arthrogryposis multiplex congenita, distal, type IIA
Camptodactyly, cleft palate, and clubfoot
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA3 features include short stature and cleft palate.
Arthrogryposis with oculomotor limitation and electroretinal abnormalities
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA5 features include ocular abnormalities, typically ptosis, ophthalmoplegia and/or strabismus, in addition to contractures of the skeletal muscles. Some patients have pulmonary hypertension as a result of restrictive lung disease.
An autosomal recessive form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA5D is characterized by severe camptodactyly of the hands, mild camptodactyly of the toes, clubfoot and/or a calcaneovalgus deformity, extension contractures of the knee, unilateral ptosis or ptosis that is more severe on one side, a round-shaped face, arched eyebrows, a bulbous upturned nose, and micrognathia. Patients do not have ophthalmoplegia.
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA7 is characterized by an inability to open the mouth fully (trismus) and pseudocamptodactyly in which wrist dorsiflexion, but not volarflexion, produces involuntary flexion contracture of distal and proximal interphalangeal joints. Additional features include shortened hamstring muscles and short stature.
Arthrogryposis, distal, with impaired proprioception and touch
A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DAIPT is an autosomal recessive disease characterized by selective loss of discriminative touch perception, ataxia, difficulty walking, dysmetria, and progressive skeletal contractures.
Arthrogryposis, impaired intellectual development, and seizures
A disease characterized by arthrogryposis, intellectual disability, autism spectrum disorder, and epilepsy. Additional features include limb malformations, distal joint involvement, microcephaly, retromicrognathia, and general muscle hypotonia.
Arthrogryposis, Perthes disease, and upward gaze palsy
An autosomal recessive, syndromic form of arthrogryposis, a disease characterized by persistent joints flexure or contracture. APUG patients manifest an unusual combination of arthrogryposis, upward gaze palsy, and avascular necrosis of the hip (Perthes disease).
Arthrogryposis, renal dysfunction and cholestasis syndrome 1
Arthrogryposis renal dysfunction and cholestasis 1
A multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common.
Arthrogryposis, renal dysfunction and cholestasis syndrome 2
Arthrogryposis renal dysfunction and cholestasis 2
Fatal X-linked ataxia with deafness and loss of vision
A disorder characterized by intellectual disability, early-onset hypotonia, ataxia, delayed motor development, hearing impairment, and optic atrophy. Susceptibility to infections, especially of the upper respiratory tract, can result in early death.
An inborn error of asparagine biosynthesis that results in a severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity.
An inborn lysosomal storage disease causing excess accumulation of glycoasparagine in the body tissues and its increased excretion in urine. Clinical features include mild to severe intellectual disability manifesting from the age of two, coarse facial features and mild connective tissue abnormalities.
A syndrome with features similar to autism. Affected individuals exhibit qualitative impairment in social interaction, as manifest by impairment in the use of non-verbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases.
A rare primary immunodeficiency and life-threatening condition, often presenting with pneumococcal sepsis. Most affected individuals die of severe bacterial infections in early childhood. Isolated asplenia is distinct from asplenia associated with other complex visceral defects, notably heterotaxy syndromes such as Ivemark syndrome.
The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi.
Asthma, with nasal polyps and aspirin intolerance
Nasal polyps asthma and aspirin sensitivity
A condition consisting of asthma, aspirin sensitivity and nasal polyposis. Nasal polyposis is due to chronic inflammation of the paranasal sinus mucosa, leading to protrusion of edematous polyps into the nasal cavities.
Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy and atopic dermatitis.
A mitochondrial disease characterized by ataxia, axonal sensorimotor polyneuropathy, abnormal eye movements, and dysarthria.
A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. Patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation.
Ataxia Friedreich-like with selective vitamin E deficiency
An autosomal recessive disease characterized by undetectable or markedly reduced plasma levels of vitamin E, spinocerebellar degeneration, ataxia, areflexia and proprioception loss.
Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus
A disease characterized by juvenile-onset diabetes and neurodegeneration, resulting in ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy.
Ataxia, intention tremor, and hypotonia syndrome, childhood-onset
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, mildly impaired intellectual development with speech delay or learning disabilities, delayed walking due to ataxia, intention tremor, and hypotonia apparent from early childhood. Brain imaging shows cerebellar atrophy in some patients.
A rare disease characterized by progressive ataxia caused by degeneration of the posterior columns of the spinal cord. Affected individuals have a reduced ability to feel pain, temperature and vibration, particularly in the hands and feet. Their most prominent feature is an ataxic gait resulting from a severe loss of proprioception. Thus, patients rely on visual cues for maintaining proper body posture, such that they are unable to remain upright if their eyes are closed (Romberg sign).
An autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy.
Ataxia early-onset with oculomotor apraxia and hypoalbuminemia
Cerebellar ataxia early-onset with hypoalbuminemia
An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.
An autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia.
A rare disorder characterized by progressive cerebellar ataxia, dysarthria, abnormal eye movements, and absence of telangiectasia. ATLD patients show normal levels of total IgG, IgA and IgM, although there may be reduced levels of specific functional antibodies. At the cellular level, ATLD exhibits hypersensitivity to ionizing radiation and radioresistant DNA synthesis.
A neurodegenerative disorder due to defects in DNA excision repair. ATLD2 is characterized by developmental delay, ataxia, sensorineural hearing loss, short stature, cutaneous and ocular telangiectasia, and photosensitivity.
Poor growth, microcephaly, developmental delay, and anemia
A form of Atelis syndrome, an autosomal recessive neurodevelopmental disorder characterized by mild to severe developmental delay, learning difficulties, microcephaly, and growth restriction with short stature. Additional features include anemia, skin hyperpigmentation, ocular anomalies, congenital heart defects, and mild skeletal abnormalities. Death in childhood may occur. Patient cells show spontaneous chromosome breakage and chromosomal anomalies, hallmarked by segmented and dicentric chromosomes and mosaic variegated hyperploidy.
Poor growth, microcephaly, dysmorphic facies, and cardiac defects
A lethal chondrodysplasia characterized by distal hypoplasia of the humeri and femurs, hypoplasia of the mid-thoracic spine, occasionally complete lack of ossification of single hand bones, and the finding in cartilage of multiple degenerated chondrocytes which are encapsulated in fibrous tissue.
A perinatal dysplasia characterized by shortening of the limbs, a dysmorphic syndrome and radiographic skeletal features. Patients are stillborn or die soon after birth.
A short-limb lethal skeletal dysplasia with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations. Recurrent respiratory insufficiency and/or infections usually result in early death.
Athabaskan brainstem dysgenesis syndrome
Characterized by horizontal gaze palsy, sensorineural deafness, central hypoventilation, and developmental delay. Some patients had swallowing dysfunction, vocal cord paralysis, facial paresis, seizures, and cardiac outflow tract anomalies.
A condition characterized by predisposition to develop hypersensitivity reactions. Atopic individuals can develop eczema, allergic rhinitis and allergic asthma.
A rare autosomal recessive disorder characterized by abnormal synthesis of transferrin leading to iron overload and microcytic hypochromic anemia.
A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
An autosomal dominant form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Patients show other heart abnormalities including ventricular and atrioventricular septal defects, pulmonary valve thickening or insufficiency of the cardiac valves. The disease is not associated with defects in the cardiac conduction system or non-cardiac abnormalities.
A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.
A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Patients show other heart abnormalities including defects in septation, chamber growth and valvulogenesis. The disease is not associated with defects in the cardiac conduction system or with non-cardiac abnormalities.
Atrial septal defect 7, with or without atrioventricular conduction defects
ASD with atrioventricular conduction defects
ASD with or without atrioventricular conduction defects
Atrial septal defect 7 with or without AV conduction defects
A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria, and atrioventricular conduction defects in some cases.
A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Some patients manifest tricuspid valve disease, pulmonary valve disease, and pulmonary artery hypertension.
Familial cardiomyopathy with conduction disturbance
A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm.
Atrial dilated cardiomyopathy with atrial standstill
An autosomal recessive disease characterized by papillary lesions over most of the body and almost complete absence of hair.
A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction.
Attention deficit-hyperactivity disorder 7
A neurobehavioral developmental disorder primarily characterized by the coexistence of attentional problems and hyperactivity, with each behavior occurring infrequently alone.
Attention deficit-hyperactivity disorder 8
A form of attention deficit-hyperactivity disorder, a neurobehavioral developmental condition primarily characterized by the coexistence of attentional problems and hyperactivity, with each feature occurring infrequently alone. ADHD8 is an autosomal recessive form with onset in early childhood, usually by age 3 years. ADHD8 patients may manifest mild developmental delay with autism.
A disorder characterized by intellectual disability, facial dysmorphism, cardiac defects, and connective tissue and skeletal abnormalities. Dysmorphic features include long palpebral fissures, ptosis, a broad prominent nasal bridge, hypoplastic alae nasi, an open downturned mouth, ears with underdeveloped and thick helices, high palate, and a unique tongue with a prominent median crease. Hypotonia, hyporeflexia, and high pain tolerance are additional features.
An autosomal recessive disease characterized by hearing loss, visual impairment and optic atrophy, with onset in the first or second decades of life. Optic atrophy is caused by degeneration of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.
Auditory neuropathy, autosomal dominant 1
Nonsyndromic auditory neuropathy autosomal dominant
A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. Affected individuals typically respond to sound but have difficulties in speech discrimination.
Auditory neuropathy, autosomal dominant 3
A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. Affected individuals typically respond to sound but have difficulties in speech discrimination. AUNA3 is a late-onset, progressive form.
Auditory neuropathy, autosomal recessive, 1
Nonsyndromic auditory neuropathy autosomal recessive
A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. In some cases AUNB1 phenotype can be temperature sensitive.
Aural atresia, congenital, with hyposmia
A rare anomaly of the ear that involves some degree of failure of the development of the external auditory canal. The malformation can also involve the tympanic membrane, ossicles and middle ear space. The inner ear development is most often normal. Different CAA forms are known. CAA type I is characterized by bony or fibrous atresia of the lateral part of the external auditory canal and an almost normal medial part and middle ear. CAA type II is the most frequent type and is characterized by partial or total aplasia of the external auditory canal. CAA type IIA involves an external auditory canal with either complete bony atresia of the medial part or partial aplasia that ends blindly in a fistula leading to a rudimentary tympanic membrane. CAA type IIB is characterized by bony stenosis of the total length of the external auditory canal. CAA type III involves bony atresia of the external auditory canal and a very small or absent middle-ear cavity.
An autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.
A craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.
A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability.
A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. AUTS16 can be associated with epilepsy.
A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. The transmission pattern of AUTS20 is consistent with autosomal dominant inheritance.
Intellectual developmental disorder, X-linked
Epsilon-trimethyllysine hydroxylase deficiency
A form of autism, a complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. AUTSX6 patients may respond favorably to carnitine supplementation.
Autoimmune disease susceptibility locus chromosome 1p-related
Vitiligo-associated multiple autoimmune disease susceptibility 2
Vitiligo-associated multiple autoimmune disease type 2
An autoimmune disorder characterized by the association of vitiligo with autoimmune thyroiditis (Hashimoto thyroiditis).
Individuals manifesting susceptibility to autoimmune disease type 6 can suffer from juvenile idiopathic arthritis, rheumatoid arthritis, multiple sclerosis, Sjogren syndrome, systemic lupus erythematosus, type 1 diabetes, ulcerative colitis, and Crohn disease.
Autoimmune disease, multisystem, infantile-onset, 1
A disorder characterized by early childhood onset of a spectrum of autoimmune manifestations affecting multiple organs, including insulin-dependent diabetes mellitus and autoimmune enteropathy or celiac disease. Other features include short stature, non-specific dermatitis, hypothyroidism, autoimmune arthritis, and delayed puberty.
Autoimmune disease, multisystem, infantile-onset, 2
An autosomal recessive, autoimmune disorder characterized by systemic manifestations including blistering skin disease, uncontrollable bullous pemphigoid, inflammatory colitis, autoimmune hypothyroidism, proteinuria and nephrotic syndrome.
Autoimmune disease, multisystem, with facial dysmorphism
Syndromic multisystem autoimmune disease
A disorder characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut.
Autoimmune interstitial lung, joint, and kidney disease
An autoimmune disease characterized by inflammatory arthritis, interstitial lung disease, and immune complex-mediated renal disease.
Autoimmune lymphoproliferative syndrome 1A
Autoimmune lymphoproliferative syndrome type IA
A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.
Autoimmune lymphoproliferative syndrome 1B
Autoimmune lymphoproliferative syndrome type IB
Autoimmune lymphoproliferative syndrome 2A
Autoimmune lymphoproliferative syndrome, type II
Autoimmune lymphoproliferative syndrome type IIA
Autoimmune lymphoproliferative syndrome 3
Autoimmune lymphoproliferative syndrome, type III
A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity.
Autoimmune polyendocrine syndrome 1, with or without reversible metaphyseal dysplasia
Autoimmune polyendocrine syndrome type I
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
Autoimmune polyendocrinopathy syndrome type I
Autosomal dominant autoimmune polyendocrinopathy syndrome type I
Hypoadrenocorticism with hypoparathyroidism and superficial moniliasis
Polyglandular autoimmune syndrome type I
Polyglandular deficiency syndrome Persian-Jewish type
A rare disease characterized by the combination of chronic mucocutaneous candidiasis, hypoparathyroidism and Addison disease. Symptoms of mucocutaneous candidiasis manifest first, followed by hypotension or fatigue occurring as a result of Addison disease. APS1 is associated with other autoimmune disorders including diabetes mellitus, vitiligo, alopecia, hepatitis, pernicious anemia and primary hypothyroidism.
A complex autoimmune disorder comprising two related diseases affecting the thyroid: Graves disease and Hashimoto thyroiditis. In both disorders, thyroid-reactive T-cells are formed and infiltrate the thyroid gland. In Graves disease, the majority of the T-cells undergo a Th2 differentiation and activate B-cells to produce antibodies against the TSH receptor, which stimulate the thyroid and cause clinical hyperthyroidism. In contrast, Hashimoto thyroiditis is characterized by Th1 switching of the thyroid-infiltrating T-cells, which induces apoptosis of thyroid follicular cells and clinical hypothyroidism.
Autoinflammation with arthritis and dyskeratosis
A disorder characterized by recurrent fever, diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Inheritance can be autosomal dominant or autosomal recessive.
Autoinflammation with episodic fever and lymphadenopathy
Cleavage-resistant RIPK1-induced autoinflammatory syndrome
An autosomal dominant immunologic disorder characterized by early onset of recurrent episodes of unexplained fever, lymphadenopathy, hepatosplenomegaly, and increased levels of inflammatory cytokines and chemokines in patient serum.
Autoinflammation with infantile enterocolitis
An autosomal dominant disorder characterized by neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of autoinflammation. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy, recurrent febrile episodes with splenomegaly, and sometimes hematologic disturbances, arthralgias, or myalgias.
Autoinflammation, antibody deficiency, and immune dysregulation
An autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies.
Autoinflammation, immune dysregulation, and eosinophilia
Atopic dermatitis, enteritis, colitis, and eosinophilia
An autosomal dominant disorder characterized by immune dysregulation, severe atopic dermatitis, and chronic gastrointestinal inflammation. Additional features include asthma, food or environmental allergies, as well as poor overall growth with short stature.
Autoinflammation, panniculitis, and dermatosis syndrome
Otulin-related autoinflammatory syndrome
An autosomal recessive autoinflammatory disorder characterized by neonatal-onset of fever, neutrophilic dermatitis, panniculitis, painful joints, failure to thrive. Patients do not exhibit overt primary immunodeficiency.
Autoinflammatory disease, systemic, X-linked
An X-linked disorder characterized by systemic autoinflammation appearing in the first months of life. Clinical manifestations are variable, including lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional features may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy.
Autoinflammatory syndrome, familial, Behcet-like 1
An autosomal dominant, autoinflammatory disorder with early onset, characterized by ulceration of mucosal surfaces, particularly in the oral and genital areas. Additional variable features include skin rash, uveitis, and polyarthritis.
Autoinflammatory syndrome, familial, with or without immunodeficiency
An autosomal dominant, autoinflammatory disorder with incomplete penetrance characterized by autoimmune cytopenia, hemolytic anemia, thrombocytopenia, and lymphadenopathy. Additional variable features may include autoimmune thyroiditis, psoriasis or eczema, nephritis, hepatitis, and symptoms of systemic lupus erythematosus. Immunodeficiency is present in some patients. Disease onset is usually in the first decades of life, although later onset has been reported.
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2
An X-linked recessive, autoinflammatory disorder characterized by ulceration of the oral mucosa and skin inflammation. Additional variable features may include gastrointestinal ulceration, arthritis, recurrent fevers, and iron deficiency anemia. Disease onset is in early childhood.
An autosomal recessive disorder characterized by severe anemia and thrombocytopenia apparent from early infancy, hepatosplenomegaly, and recurrent fevers associated with a hyperinflammatory state. Additional systemic features may include chronic diarrhea, proteinuria with renal disease, liver fibrosis with elevated liver enzymes, deforming arthropathy, and vasculitic skin lesions. Some patients may have motor delay or learning difficulties associated with subcortical white matter lesions on brain imaging.
Avascular necrosis of femoral head, primary, 1
A disease characterized by mechanical failure of the subchondral bone, and degeneration of the hip joint. It usually leads to destruction of the hip joint in the third to fifth decade of life. The clinical manifestations, such as pain on exertion, a limping gait, and a discrepancy in leg length, cause considerable disability. ANFH1 inheritance is autosomal dominant.
Avascular necrosis of the femoral head, primary 2
A disease characterized by mechanical failure of the subchondral bone, and degeneration of the hip joint. It usually leads to destruction of the hip joint in the third to fifth decade of life. The clinical manifestations, such as pain on exertion, a limping gait, and a discrepancy in leg length, cause considerable disability.
Iridogoniodysgenesis with somatic anomalies
An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Additional features include aniridia, maxillary hypoplasia, hypodontia, anal stenosis, redundant periumbilical skin.
Axenfeld-Rieger anomaly with cardiac defects and/or sensorineural hearing loss
Axenfeld-Rieger anomaly with or without cardiac defects and/or sensorineural hearing loss
An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Features include posterior corneal embryotoxon, prominent Schwalbe line and iris adhesion to the Schwalbe line, hypertelorism, hypodontia, sensorineural deafness, redundant periumbilical skin, and cardiovascular defects such as patent ductus arteriosus and atrial septal defect. When associated with tooth anomalies, the disorder is known as Rieger syndrome.
A multisystem disorder characterized by congenital cataracts, sensorineural deafness, intellectual disability, seizures, brachycephaly, distinctive flat facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced growth.
Azoospermia, obstructive, with nephrolithiasis
An X-linked recessive, male infertility disorder characterized by epidydimal obstruction, hypercalciuria and kidney stones.
B-cell expansion with NFKB and T-cell anergy
An autosomal dominant condition characterized by onset in infancy of splenomegaly and polyclonal expansion of B cells, resulting in peripheral lymphocytosis. Affected individuals also show mild immune dysfunction, including some defective antibody responses and T-cell anergy. There may be a predisposition to the development of B-cell malignancy.
B-cell immunodeficiency, distal limb anomalies, and urogenital malformations
An autosomal dominant disorder characterized by humoral immunodeficiency with undetectable B cells, distal limb anomalies, dysmorphic facial features, and urogenital malformations.
Neurodevelopmental disorder with alopecia and brain abnormalities
An autosomal dominant disorder characterized by global developmental delay, alopecia, absolute or relative macrocephaly, and facial dysmorphism. Neuroimaging shows white matter abnormalities, prominent Virchow-Robin spaces, periventricular cysts, and abnormalities of the corpus callosum.
A syndrome characterized by psychomotor retardation, feeding problems, severe postnatal growth retardation in some patients, arched eyebrows, anteverted nares, and ulnar deviation of the hands.
Neurodevelopmental disorder with involuntary movement and abnormal electroencephalogram
An autosomal dominant neurodevelopmental disorder characterized by infantile hypotonia, congenital ophthalmic abnormalities, involuntary and hyperkinetic movements, stereotypic behavior, poor or absent speech, EEG abnormalities, and global developmental delay varying in severity from moderate to profound. Behavioral characteristics include sleep disturbance and episodic agitation.
Craniosynostosis-radial aplasia syndrome
An autosomal recessive syndrome characterized by short stature, craniosynostosis, absent or hypoplastic radii, short and curved ulna, fused carpal bones and absent carpals, metacarpals and phalanges. Some patients manifest poikiloderma. Cases reported as Baller-Gerold syndrome have phenotypic overlap with several other disorders, including Saethre-Chotzen syndrome.
Athyroidal hypothyroidism with spiky hair and cleft palate
An autosomal recessive disease characterized by congenital hypothyroidism due to thyroid agenesis or thyroid hypoplasia, cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis.
A brain malformation of the lissencephaly spectrum, resulting from disordered neuronal migration and characterized by bands of gray matter interposed in the central white matter. Disease features include severe developmental delay with intellectual disability, enlarged head circumference, periventricular and ribbon-like subcortical heterotopia, polymicrogyria and agenesis of the corpus callosum.
A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.
Neurodevelopmental disorder with cataracts and variable microcephaly
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and difficulty walking or inability to walk. Affected individuals have early-onset cataracts. Additional variable features are microcephaly, facial dysmorphism, metabolic abnormalities, spasticity, and lymphopenia.
Hypertrichosis, atrophic skin, ectropion, and macrostomia
A rare ectodermal dysplasia characterized by ectropion, macrostomia, ear abnormalities, broad nasal bridge, bulbous nose, redundant skin, hypertrichosis, dental abnormalities, and variable other features.
A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease.
A form of Bardet-Biedl syndrome, a syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease.
A HLA class I deficiency. Contrary to bare lymphocyte syndromes type 2 and type 3, which are characterized by early-onset severe combined immunodeficiency, class I antigen deficiencies are not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract.
Bare lymphocyte syndrome type II complementation group A
Bare lymphocyte syndrome type II complementation group B
Bare lymphocyte syndrome type II complementation group C
Bare lymphocyte syndrome type II complementation group D
Bare lymphocyte syndrome type II complementation group E
HLA class II deficient combined immunodeficiency
Major histocompatibility complex class II deficiency
Severe combined immunodeficiency HLA class II-negative
A severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon-gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections.
A condition characterized by a metaplastic change in which normal esophageal squamous epithelium is replaced by a columnar and intestinal-type epithelium. Patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett esophagus is gastroesophageal reflux. The retrograde movement of acid and bile salts from the stomach into the esophagus causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes.
Knuckle pads, leukonychia, and sensorineural deafness
An autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability.
3-alpha-methylglutaconic aciduria type 2
Cardioskeletal myopathy with neutropenia and abnormal mitochondria
Left ventricular non-compaction isolated X-linked
Non-compaction of left ventricular myocardium isolated X-linked
An X-linked disease characterized by dilated cardiomyopathy with endocardial fibroelastosis, a predominantly proximal skeletal myopathy, growth retardation, neutropenia, and organic aciduria, particularly excess of 3-methylglutaconic acid. Additional features include hypertrophic cardiomyopathy, isolated left ventricular non-compaction, ventricular arrhythmia, motor delay, poor appetite, fatigue and exercise intolerance, hypoglycemia, lactic acidosis, hyperammonemia, and dramatic late catch-up growth after growth delay throughout childhood.
Popliteal pterygium syndrome, lethal type
An autosomal recessive disorder characterized by multiple popliteal pterygia leading to severe arthrogryposis, ankyloblepharon filiforme adnatum, filiform bands between the jaws, synostosis of the carpal/tarsal and phalangeal bones in the hands and feet, digital hypoplasia/aplasia, complete soft-tissue syndactyly, lack of nails, lack of scalp hair, eyebrows and eyelashes, blepharophimosis, cleft lip and/or palate, and hypoplastic external genitalia. Early lethality is common, although survival into childhood and beyond has been reported.
Popliteal pterygium syndrome, Bartsocas-Papas type 2
An autosomal recessive, severe form of popliteal pterygium syndrome. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but they are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations.
Hypokalemic alkalosis with hypercalciuria antenatal 1
A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS1 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia.
Hypokalemic alkalosis with hypercalciuria antenatal 2
A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS2 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia.
A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria.
Bartter syndrome 4A, neonatal, with sensorineural deafness
Bartter syndrome, neonatal, with sensorineural deafness
Hypokalemic alkalosis with hypercalciuria antenatal 4
Infantile Bartter syndrome with sensorineural deafness
Sensorineural deafness with mild renal dysfunction
A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS4A is associated with sensorineural deafness.
Bartter syndrome 4B, neonatal, with sensorineural deafness
A digenic form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS4B is associated with sensorineural deafness.
Bartter syndrome 5, antenatal, transient
Bartter syndrome, type 5, antenatal, transient
An X-linked recessive form of Bartter syndrome, a disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS5 is an antenatal form beginning in utero with marked fetal polyuria that leads to polyhydramnios and premature delivery. It is characterized by severe but transient symptoms that can resolve with age.
A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. BCC is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.
A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.
Gorlin syndrome or Gorlin-Goltz syndrome
An autosomal dominant disease characterized by nevoid basal cell carcinomas and developmental abnormalities such as rib and craniofacial alterations, polydactyly, syndactyly, and spina bifida. In addition, the patients suffer from a multitude of tumors like basal cell carcinomas, fibromas of the ovaries and heart, cysts of the skin, jaws and mesentery, as well as medulloblastomas and meningiomas.
Basal ganglia calcification, idiopathic, 1
Autosomal dominant adult-onset striopallidodentate calcinosis
Bilateral striopallidodentate calcinosis
Idiopathic basal ganglia calcification 2
Idiopathic basal ganglia calcification 3
Non-arteriosclerotic, idiopathic, adult-onset cerebral calcification
A form of basal ganglia calcification, an autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas.
Basal ganglia calcification, idiopathic, 4
Basal ganglia calcification, idiopathic, 5
Basal ganglia calcification, idiopathic, 6
Basal ganglia calcification, idiopathic, 7, autosomal recessive
A form of basal ganglia calcification, a genetically heterogeneous condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas.
Basal ganglia calcification, idiopathic, 8, autosomal recessive
Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.
Adermatoglyphia with congenital facial milia and acral blisters, digital contractures, and nail abnormalities
Ectodermal dysplasia, absent dermatoglyphic pattern, changes in nails, and simian crease
An autosomal dominant form of adermatoglyphia associated with congenital facial milia, acral blistering, digital contractures, and nail abnormalities. Adermatoglyphia is defined by the lack of epidermal ridges on the palms and soles, which results in the absence of fingerprints.
An autosomal recessive syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability.
An X-linked syndrome characterized by intellectual disability, global developmental delay, progressive gait disturbance, poor or absent speech, facial dysmorphism, and mild distal skeletal anomalies.
Intellectual developmental disorder and hypogonadotropic hypogonadism
An autosomal recessive disorder characterized by obesity, intellectual disability, and hypogonadotropic hypogonadism. Additional variable features include central hypothyroidism, hypotonia, and developmental delay.
Cutis gyrata syndrome of Beare and Stevenson
An autosomal dominant disease characterized by craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet.
An autosomal recessive neurodevelopmental disorder characterized by delayed development, moderate intellectual disability, and dysmorphic facial features. Other developmental anomalies, such as cardiac and renal defects, may also occur.
A developmental disorder characterized by mild to severe intellectual disability, global developmental delay, hypotonia, autistic traits, movement disorders, growth abnormalities including overgrowth or poor growth, and facial dysmorphism. Both autosomal dominant and autosomal recessive inheritance has been reported.
A neuromuscular disorder characterized by dystrophin deficiency. It appears between the age of 5 and 15 years with a proximal motor deficiency of variable progression. Heart involvement can be the initial sign. Becker muscular dystrophy has a more benign course than Duchenne muscular dystrophy.
Exomphalos-macroglossia-gigantism syndrome
A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors.
Infantile hereditary optic atrophy with neurologic abnormalities
Optic atrophy, infantile hereditary, with neurologic abnormalities
An autosomal recessive syndrome characterized by optic atrophy beginning in early childhood associated with ataxia, pyramidal signs, spasticity, intellectual disability, and posterior column sensory loss. The ataxia, spasticity, and muscle contractures, mainly of the hip adductors, hamstrings, and soleus, are progressive and become more prominent in the second decade.
A primary focal dystonia affecting the orbicularis oculi muscles. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. BEB usually begins in middle age. Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. Patients have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids. In severe cases, this can lead to functional blindness.
A perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.
An autosomal recessive bone dysplasia characterized by defects in both the axial and appendicular skeleton, with radiographic findings showing undermineralized bone and a distinct angulation of the mid femoral shaft. Extraskeletal features include facial dysmorphisms, abnormally formed ears with tags, wide spaced nipples, and atrial septal defects. Elbow fusions, ulnar flexion contractions at the wrist, bilateral talipes equinovarus, and failure to mount a respiratory effort at birth suggest abnormalities in muscle function.
Von Willebrand factor receptor deficiency
A coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, thrombocytopenia, and impaired prothrombin consumption.
Bernard-Soulier syndrome A2, autosomal dominant
Autosomal dominant benign Bernard-Soulier syndrome
Benign mediterranean macrothrombocytopenia
A coagulation disorder characterized by mild to moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. Some individuals have no symptoms. Mild bleeding tendencies manifest as epistaxis, gingival bleeding, menorrhagia, easy bruising, or prolonged bleeding after dental surgery.
A retinopathy characterized by loss of central vision, an absent electro-oculogram light rise, and electroretinogram anomalies.
A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of detectable beta globin causes beta(+)-thalassemia. In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate severity), and thalassemia minor that is asymptomatic.
Beta-thalassemia, dominant, inclusion body type
Beta thalassemia dominant inclusion body type
Dyserythropoietic anemia congenital Irish or Weatherall type
An autosomal dominant form of beta thalassemia characterized by moderate anemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphologic changes in the red cells, erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow and in the peripheral blood after splenectomy.
An inborn error of metabolism due to a defect in pyrimidine degradation. It is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay. Patients show strongly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine.
Muscular dystrophy, limb-girdle, autosomal dominant 5
Myopathy, benign congenital, with contractures
A benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles.
A form of Bethlem myopathy, a benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. BTHLM2 inheritance is autosomal dominant.
A severe progressive degenerative osteoarthritis of the hip joint with underlying dysplasia confined to that region. Affected individuals are of normal stature and have no associated health problems.
Bietti crystalline corneoretinal dystrophy
Bietti tapetoretinal degeneration with marginal corneal dystrophy
An autosomal recessive ocular disease characterized by retinal degeneration and marginal corneal dystrophy. Typical features include multiple glistening intraretinal crystals scattered over the fundus, a characteristic degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field. Most patients have similar crystals at the corneoscleral limbus. Patients develop decreased vision, nyctalopia, and paracentral scotomata between the 2nd and 4th decade of life. Later, they develop peripheral visual field loss and marked visual impairment, usually progressing to legal blindness by the 5th or 6th decade of life.
Bifid nose, with or without anorectal and renal anomalies
Bifid nose renal agenesis and anorectal malformations syndrome
A disease characterized by the presence of a bifid nose usually associated with renal agenesis and anorectal malformations. A bifid nose is a congenital deformity due to failure of the paired nasal processes to fuse to a single midline organ during early gestation.
A congenital anomaly in which the optic disk appears abnormally small. It may be an isolated finding or part of a spectrum of anatomic and functional abnormalities that includes partial or complete agenesis of the septum pellucidum, other midline brain defects, cerebral anomalies, pituitary dysfunction, and structural abnormalities of the pituitary.
An autosomal recessive metabolic disorder characterized by reduced biliary secretion of conjugated bile acids, fat malabsorption, and fat-soluble vitamin deficiency. Clinical manifestations include rickets with variable growth failure due to vitamin D deficiency, and coagulopathy due to deficiency of vitamin K-dependent clotting factors. Additional variable features include pruritis, anemia, hepatomegaly, and bile duct proliferation on liver biopsy. Laboratory studies show abnormally increased levels of unconjugated bile acids.
An autosomal recessive intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, steatorrhea and interruption of the enterohepatic circulation of bile acids.
An autosomal recessive disorder characterized by chronic diarrhea, severe fat-soluble vitamin deficiency, and features of cholestatic liver disease.
Biliary, renal, neurologic, and skeletal syndrome
An autosomal recessive ciliopathy with multisystemic manifestations including severe neonatal cholestasis that progresses to liver fibrosis and cirrhosis, postaxial polydactyly, hydrocephalus, retinal abnormalities, and situs inversus. Additional features may include congenital cardiac defects, echogenic kidneys with renal failure, ocular abnormalities, joint hyperextensibility, and dysmorphic facial features. Some patients have global developmental delay. Brain imaging typically shows dilated ventricles, hypomyelination, and white matter abnormalities, although some patients have been described with abnormal pituitary development.
Late-onset multiple carboxylase deficiency
Multiple carboxylase deficiency, juvenile-onset
Multiple carboxylase deficiency, late-onset
A juvenile form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. Biotinidase deficiency is characterized by seizures, hypotonia, skin rash, alopecia, ataxia, hearing loss, and optic atrophy. If untreated, symptoms usually become progressively worse, and coma and death may occur.
A condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules, Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity.
A syndrome characterized by intellectual disability, hypotonia, hyperactivity, and facial dysmorphism. BIBARS transmission pattern is consistent with autosomal dominant inheritance with paternal imprinting.
An autosomal recessive syndrome characterized by early-childhood onset of different combinations of intellectual disability, muscle weakness, camptocormia, oculomotor apraxia, and nephropathy.
Fibrofolliculomas with trichodiscomas and acrochordons
A rare autosomal dominant genodermatosis characterized by hair follicle hamartomas (fibrofolliculomas), kidney tumors, and spontaneous pneumothorax. Fibrofolliculomas are part of the triad of Birt-Hogg-Dube syndrome skin lesions that also includes trichodiscomas and acrochordons. Onset of this dermatologic condition is invariably in adulthood. Birt-Hogg-Dube syndrome is associated with a variety of histologic types of renal tumors, including chromophobe renal cell carcinoma (RCC), benign renal oncocytoma, clear-cell RCC and papillary type I RCC. Multiple lipomas, angiolipomas, and parathyroid adenomas are also seen in Birt-Hogg-Dube syndrome patients.
An autosomal recessive disease characterized by congenital sensorineural hearing loss and twisted hairs (pili torti). Pili torti is a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle.
A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.
Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT
An autosomal recessive disease characterized by impaired innervation and autonomic dysfunction of the urinary bladder, hydronephrosis, vesicoureteral reflux, small kidneys, recurrent urinary tract infections, and progressive renal insufficiency. Additional autonomic features are impaired pupillary reflex and orthostatic hypotension. The disease manifests in utero or early childhood.
Familial granulomatous inflammatory arthritis dermatitis and uveitis
Familial juvenile systemic granulomatosis
An autosomal dominant inflammatory disorder characterized by the formation of immune granulomas invading the skin, joints and eye. Other organs may be involved. Clinical manifestations are variable and include early-onset granulomatous arthritis, uveitis and skin rash. Blindness, joint destruction and visceral involvement have been reported in severe cases.
A mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen.
Bleeding disorder due to defective platelet thromboxane A2 receptor
A disorder characterized by reduced platelet aggregation and a tendency to mild mucocutaneous bleeding.
Autosomal dominant macrothrombocytopenia ACTN1-related
An autosomal dominant form of macrothrombocytopenia. Affected individuals usually have no or only mild bleeding tendency, such as epistaxis. Laboratory studies show decreased numbers of large platelets and anisocytosis, but the platelets show no in vitro functional abnormalities.
Glanzmann thrombasthenia-like with macrothrombocytopenia 1
An autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities.
Autosomal dominant macrothrombocytopenia GFI1B-related
Autosomal dominant platelet disorder GFI1B-related
Hereditary thrombasthenia-thrombocytopenia
An autosomal dominant disorder characterized by increased bleeding tendency due to platelet dysfunction, and associated with macrothrombocytopenia and red cell anisopoikilocytosis. Platelets appear abnormal on light microscopy, while electron microscopy shows a heterogeneous decrease of alpha granules within platelets. Bone marrow biopsy shows increased numbers of abnormal megakaryocytes, suggesting a defect in megakaryopoiesis and platelet production. The severity of bleeding is variable with some affected individuals experiencing spontaneous bleeding while other exhibit only abnormal bleeding with surgery.
A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia.
A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. BDPLT20 is characterized by moderate thrombocytopenia and platelet secretion defects. Inheritance is autosomal dominant.
A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. BDPLT21 patients may have mild to moderate thrombocytopenia.
An autosomal recessive disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after minor injuries, and menorrhagia.
Bleeding disorder, platelet-type, 24, autosomal dominant
Glanzmann thrombasthenia-like with macrothrombocytopenia 2
An autosomal dominant disorder of platelet production characterized by congenital macrothrombocytopenia and platelet anisocytosis. Affected individuals may have no or only mildly increased bleeding tendency.
A condition characterized by mild to moderate mucocutaneous bleeding, and excessive bleeding after surgery or trauma. The defect is due to severe impairment of platelet response to ADP resulting in defective platelet aggregation.
Ectropion, inferior, with cleft lip and/or palate
Lagophthalmia with bilateral cleft lip and palate
A form of blepharocheilodontic syndrome, a rare autosomal dominant disorder. It is characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and features of ectodermal dysplasia, including hair anomalies, conical teeth and tooth agenesis. An additional rare manifestation is imperforate anus. There is considerable phenotypic variability among affected individuals.
Blepharophimosis, ptosis, and epicanthus inversus syndrome
A disorder characterized by eyelid dysplasia, small palpebral fissures, drooping eyelids and a skin fold curving in the mediolateral direction, inferior to the inner canthus. In type I BPSE (BPES1) eyelid abnormalities are associated with female infertility. Affected females show an ovarian deficit due to primary amenorrhea or to premature ovarian failure (POF). In type II BPSE (BPES2) affected individuals show only the eyelid defects.
Blepharophimosis-impaired intellectual development syndrome
An autosomal dominant congenital syndrome characterized by blepharophimosis, facial dysmorphism, global development delay, delayed motor skills, impaired intellectual development with poor or absent speech, and behavioral abnormalities in some patients. Additional variable features include distal skeletal anomalies, feeding difficulties with poor growth, respiratory infections, and hypotonia with peripheral spasticity.
Blistering, acantholytic, of oral and laryngeal mucosa
An autosomal recessive disorder characterized by recurrent, suprabasal acantholytic blisters in the oral and laryngeal mucosa. Skin, conjunctival and genital mucosa, nail folds, and nails are unaffected. Normal structure is observed in the scalp epidermis and hair follicle.
Microcephaly, growth restriction, and increased sister chromatid exchange 1
An autosomal recessive disorder. It is characterized by proportionate pre- and postnatal growth deficiency, sun-sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability.
Colorblindness blue-mono-cone-monochromatic type
A rare X-linked congenital stationary cone dysfunction syndrome characterized by the absence of functional long wavelength-sensitive and medium wavelength-sensitive cones in the retina. Color discrimination is severely impaired from birth, and vision is derived from the remaining preserved blue (S) cones and rod photoreceptors. BCM typically presents with reduced visual acuity, pendular nystagmus, and photophobia. Patients often have myopia.
Mental deficiency-epilepsy- endocrine disorders
An X-linked recessive disorder characterized by moderate to severe intellectual disability, epilepsy, hypogonadism, hypometabolism, obesity with marked gynecomastia, swelling of subcutaneous tissue of the face, narrow palpebral fissure and large but not deformed ears.
A syndrome characterized by severe intrauterine growth retardation, poor feeding, profound intellectual disability, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints.
Bone fragility with contractures, arterial rupture, and deafness
An autosomal recessive connective tissue disorder, secondary to lysyl hydroxylase 3 deficiency. It is characterized by congenital malformations severely affecting multiple tissues and organs. Clinical features include growth retardation, craniofacial dysmorphism, popliteal and cerebral aneurysm, cerebral arterial hemorrhage, skin blistering and easy bruisability, and osteopenia.
Bone marrow failure and diabetes mellitus syndrome
A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFDMS is an autosomal recessive form characterized by various degrees of bone marrow failure, ranging from dyserythropoiesis to bone marrow aplasia, with onset in infancy or early childhood, and non-autoimmune insulin-dependent diabetes mellitus appearing in the first or second decades. Many patients show pigmentary skin abnormalities and short stature.
An autosomal dominant disease characterized by aplastic anemia and myelodysplasia resulting from bone marrow failure. Aplastic anemia is a form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. Myelodysplasia is a clonal hematopoietic stem cell disorder in which immature cells in the bone marrow become malformed and dysfunctional.
An autosomal recessive disorder characterized by trilineage bone marrow failure, bone marrow hypocellularity, learning difficulties, and microcephaly. Insufficient hematopoiesis results in peripheral blood cytopenias, affecting myeloid, erythroid and megakaryocyte lines. Cutaneous features and increased chromosome breakage are not features.
A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS3 is characterized by pancytopenia with onset in early childhood. Some patients have additional variable non-specific features, including poor growth, microcephaly, and skin anomalies. BMFS3 inheritance is autosomal recessive.
A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS4 is characterized by early-onset anemia, leukopenia, decreased B cells, and developmental aberrations including facial dysmorphism, mild skeletal anomalies, and neurodevelopmental delay. BMFS4 inheritance is autosomal recessive.
A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS5 is an autosomal dominant form characterized by infantile onset of severe red cell anemia requiring transfusion. Additional features include hypogammaglobulinemia, poor growth with microcephaly, developmental delay, and seizures.
A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer.
A perinatal lethal osteochondrodysplasia characterized by absence or underossification of the limb bones and vertebrae. Patients manifest dwarfism with short, bowed, rigid limbs and characteristic facies. Boomerang dysplasia is distinguished from atelosteogenesis on the basis of a more severe defect in mineralization, with complete absence of ossification in some limb elements and vertebral segments.
Bosch-Boonstra-Schaaf optic atrophy syndrome
An autosomal dominant disorder characterized by optic atrophy associated with developmental delay and intellectual disability. Most patients also have evidence of cerebral visual impairment.
A disease characterized by horizontal gaze abnormalities, deafness, facial weakness, vascular malformations of the internal carotid arteries and cardiac outflow trac. Some patients manifest intellectual disability and autism spectrum disorder. Affected individuals do not suffer from central hypoventilation.
Arhinia, choanal atresia, microphthalmia, and hypogonadotropic hypogonadism
Congenital absence of nose and anterior nasopharynx
An autosomal dominant syndrome characterized by severe hypoplasia of the nose, palatal abnormalities, hypoplasia of the eyes, sensory abnormalities of taste and smell, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence.
A type of retinitis punctata albescens. Affected individuals show night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration.
Spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy
An autosomal recessive disorder characterized by spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop 1 or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present.
Tall stature and long digits with extra epiphyses
An autosomal recessive disorder characterized by tall stature, long digits, and extra epiphyses in the hands and feet. In addition, some patients show joint hypermobility and dilation of the aortic root.
A combination of malformations characterized in newborns by low birth weight, microcephaly, mild joint restriction, a prominent nose, micrognathia, fifth finger clinodactyly, and 'rocker-bottom' feet. The syndrome is transmitted as an autosomal recessive trait. The prognosis is poor, with all infants dying within the first few months of life.
Brachycephaly, trichomegaly, and developmental delay
An autosomal dominant developmental disorder characterized by brachycephaly, ciliary trichomegaly, dysmorphic features of the face and hands, hearing loss, and developmental delay with short stature. Intellectual disability and autism spectrum disorder may be present in some patients.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1 inheritance is autosomal dominant.
A form of brachydactyly type A1. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1C inheritance can be autosomal dominant or autosomal recessive. Autosomal dominant BDA1C has a milder phenotype.
A form of brachydactyly type A1. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1D inheritance is autosomal dominant.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type B1 the middle phalanges are short but in addition the terminal phalanges are rudimentary or absent. Both fingers and toes are affected. The thumbs and big toes are usually deformed. Symphalangism is also a feature.
A form of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones and partial cutaneous syndactyly.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type C is characterized by deformity of the middle and proximal phalanges of the second and third fingers, sometimes with hypersegmentation of the proximal phalanx. The ring finger may be essentially normal and project beyond the others.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type D is characterized by short and broad terminal phalanges of the thumbs and big toes.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. Brachydactyly type E1 is characterized by shortening limited to fourth metacarpals and/or metatarsals.
A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. Wide variability in the number of digits affected occurs from person to person, even in the same family. Some individuals are moderately short of stature. In brachydactyly type E2 variable combinations of metacarpals are involved, with shortening also of the first and third distal and the second and fifth middle phalanges.
A disease characterized by generalized shortening of the hands and feet, broad and short distal phalanges of the thumbs, and cutaneous syndactyly of toes 2 and 3. The limb phenotypes observed in this syndrome overlap those of brachydactyly types A4, D, E and syndactyly type 1.
Brachydactyly-syndactyly-oligodactyly syndrome
A syndrome characterized by a complex brachydactyly-syndactyly-oligodactyly phenotype. Limb anomalies include reduced number of digits that are severely shortened, camptodactyly, syndactyly, absence of terminal phalanges of the thumbs, and absence of nails of the thumbs and toes.
A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly. BCYM3 is an autosomal dominant form with severe scoliosis with or without kyphosis, and flattened irregular cervical vertebrae.
Brachyolmia type 4 with mild epiphyseal and metaphyseal changes
Spondylodysplasia and premature pubarche
Spondylometaepiphyseal dysplasia Pakistani type
A form of brachyolmia, a clinically and genetically heterogeneous skeletal dysplasia primarily affecting the spine and characterized by a short trunk, short stature, and platyspondyly. BCYM4 is an autosomal recessive form with mild epiphyseal and metaphyseal changes. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some BCYM4 patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature.
An autosomal recessive disease characterized by microcephaly, congenital thrombocytopenia, and facial dysmorphisms including Pierre-Robin sequence.
Brain abnormalities, neurodegeneration, and dysosteosclerosis
An autosomal recessive disease with variable manifestations. Main features are brain malformations with calcifying leukoencephalopathy, progressive neurodegeneration, and bone sclerotic features. The age at onset ranges from infancy to early adulthood. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum.
Brain malformations with or without urinary tract defects
A syndrome characterized by corpus callosum hypoplasia or agenesis, hydrocephalus or ventricular enlargement, developmental delay, and urinary tract defects.
Brain small vessel disease 1 with or without ocular anomalies
Brain small vessel disease with Axenfeld-Rieger anomaly
Brain small vessel disease with hemorrhage
Leukoencephalopathy with Axenfeld-Rieger anomaly
Retinal arteriolar tortuosity, infantile hemiparesis, and leukoencephalopathy, autosomal dominant
An autosomal dominant cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD1 features include cerebral hemorrage, unilateral fluid-filled cysts or cavities within the cerebral hemispheres, leukoencephalopathy, hemiplegia, seizures, intellectual disability, and facial paresis. Affected individuals may manifest variable visual defects and ocular anomalies.
An autosomal dominant cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD2 features include intracranial hemorrage, fluid-filled cysts or cavities within the cerebral hemispheres, delayed psychomotor development, hemiplegia, spasticity and seizures.
An autosomal recessive form of brain small vessel disease, a cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD3 patients may have disease onset in utero or early infancy with subsequent global developmental delay, spasticity, and porencephaly on brain imaging. Other patients may have normal or mildly delayed development with sudden onset of intracranial hemorrhage causing acute neurologic deterioration.
Branched-chain ketoacid dehydrogenase kinase deficiency
A metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids.
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome
An autosomal dominant disorder characterized by choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, delayed or absent pubertal development, and thyroid abnormalities. Additional features may include developmental delay, growth failure and short stature.
Branchial clefts with characteristic facies growth retardation imperforate nasolacrimal duct and premature aging
Hemangiomatous branchial clefts-lip pseudocleft syndrome
Lip pseudocleft-hemangiomatous branchial cyst syndrome
A syndrome characterized by growth retardation, bilateral branchial sinus defects with hemangiomatous, scarred skin, cleft lip with or without cleft palate, pseudocleft of the upper lip, nasolacrimal duct obstruction, low set ears with posterior rotation, a malformed, asymmetrical nose with a broad bridge and flattened tip, conductive or sensorineural deafness, ocular and renal anomalies.
A syndrome characterized by usually bilateral branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, and structural defects of the outer, middle or inner ear. Otic defects include malformed and hypoplastic pinnae, a narrowed external ear canal, bulbous internal auditory canal, stapes fixation, malformed and hypoplastic cochlea. Branchial and otic anomalies overlap with those seen in individuals with the branchiootorenal syndrome. However renal anomalies are absent in branchiootic syndrome patients.
A syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations.
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
A type of breast cancer that begins in the milk-producing glands (lobules) of the breast.
A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.
Corneal fragility keratoglobus blue sclerae joint hyperextensibility
Dysgenesis mesodermalis corneae et sclerae
Ehlers-Danlos syndrome type VIB formerly
Fragilitas oculi with joint hyperextensibility
A disorder characterized by extreme corneal thinning resulting in corneal rupture after minor trauma, blue sclerae, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints. It shares some features with, but is much less severe than, the ocular form of Ehlers-Danlos syndrome (EDS6).
A disorder characterized by extreme corneal thinning resulting in corneal rupture after minor trauma, blue sclerae, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobile joints.
An autosomal recessive muscular disorder characterized by exercise-induced muscle stiffness and cramps primarily affecting the arms, legs, and eyelids, although more generalized muscle involvement may also occur.
Bronchiectasis with or without elevated sweat chloride 1
A debilitating respiratory disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases.
Bronchiectasis with or without elevated sweat chloride 2
Bronchiectasis with or without elevated sweat chloride 3
An autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life.
Bulbar palsy progressive with sensorineural deafness
A rare neurologic disorder characterized by sensorineural hearing loss and a variety of cranial nerve palsies, which develop over a relatively short period of time in a previously healthy individual. Sensorineural hearing loss may precede the neurological signs. The course is invariably progressive, but the rate of decline is variable within and between families. With disease evolution, long tract signs, lower motor neuron signs, cerebellar ataxia and lower cranial nerve (III-VI) palsies develop, giving rise to a complex picture resembling amyotrophic lateral sclerosis. Diaphragmatic weakness and respiratory compromise are some of the most distressing features, leading to recurrent chest infections and respiratory failure, which are often the cause of patients' demise.
An autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting resulting in respiratory insufficiency and loss of independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation.
A disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia.
Osteogenesis imperfecta with congenital joint contractures
An autosomal recessive disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia. It is distinguished from osteogenesis imperfecta by the absence of hearing loss and dentinogenesis imperfecta, and by the presence of clubfoot and congenital joint limitations.
A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
A heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
Brunet-Wagner neurodevelopmental syndrome
An autosomal recessive disorder characterized by severe developmental delay, intellectual disability, poor or absent speech, infantile hypotonia, inability to walk, behavioral abnormalities, and dysmorphic features.
A form of X-linked non-dysmorphic mild intellectual disability. Male patients are affected by borderline intellectual deficit and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior.
Bryant-Li-Bhoj neurodevelopmental syndrome 1
An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects.
Bryant-Li-Bhoj neurodevelopmental syndrome 2
Membranous obstruction of the inferior vena cava
A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera.
A psychiatric disorder characterized by eating an unusually large amount of food in a short period of time, followed by inappropriate acts (purging) to avert weight gain. Compensatory behavior includes self-induced vomiting, laxative abuse, and excessive exercise.
An autosomal dominant neurodevelopmental disorder characterized by hypotonia apparent in early infancy, global developmental delay, delayed walking, language and speech delay, impaired intellectual development, and dysmorphic facial features.
A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass.
A disease characterized by choanal atresia, sensorineural deafness, cardiac defects, and typical craniofacial dysmorphism consisting of narrow palpebral fissures, coloboma of the lower eyelids, prominent nose with high nasal bridge, short philtrum, cleft lip and/or palate, and large and protruding ears. Intellectual development is normal.
Dermatofibrosis lenticularis disseminata with osteopoikilosis
Disseminated dermatofibrosis with osteopoikilosis
A disease characterized by osteopoikilosis and disseminated connective-tissue nevi. Osteopoikilosis is a skeletal dysplasia characterized by a symmetric but unequal distribution of multiple hyperostotic areas in different parts of the skeleton. Elastic-type nevi (juvenile elastoma) and collagen-type nevi (dermatofibrosis lenticularis disseminata) have been described in BOS. Skin or bony lesions can be absent in some family members, whereas other relatives may have both.
Fluoride-resistant butyrylcholinesterase deficiency Japanese type
Fluoride-resistant hypocholinesterasemia Japanese type
An autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency.
A syndrome characterized by trigonocephaly, severe intellectual disability, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears.
An autosomal dominant disorder characterized by an infantile episode of massive subperiosteal new bone formation that typically involves the diaphyses of the long bones, mandible, and clavicles. The involved bones may also appear inflamed, with painful swelling and systemic fever often accompanying the illness. The bone changes usually begin before 5 months of age and resolve before 2 years of age.
A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands.
Calvarial doughnut lesions with bone fragility
A rare autosomal dominant bone disease characterized by low bone density, distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. Patients present with childhood onset of primary osteoporosis and typical sclerotic doughnut-shaped lesions in the cranial bones.
Calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia
A severe form of calvarial doughnut lesions with bone fragility, a rare autosomal dominant disease characterized by low bone density, distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. CDLSMD patients show neonatal onset of fractures, severe short stature, marked cranial sclerosis, and spondylometaphyseal dysplasia.
Acampomelic campomelic dysplasia with autosomal sex reversal
Campomelic dysplasia with autosomal sex reversal
A rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females.
Camptodactyly, tall stature, and hearing loss syndrome
An autosomal dominant syndrome characterized by permanent and irreducible flexion of one or more fingers of the hand and/or feet, tall stature, scoliosis and/or a pectus excavatum, and hearing loss. Affected individuals have developmental delay and/or intellectual disability, and several of these have microcephaly. Radiographic findings included tall vertebral bodies with irregular borders and broad femoral metaphyses with long tubular shafts. On audiological exam, each tested member have bilateral sensorineural hearing loss and absent otoacoustic emissions. The hearing loss was congenital or developed in early infancy, progressed variably in early childhood, and range from mild to severe. Computed tomography and magnetic resonance imaging reveal that the brain, middle ear, and inner ear are structurally normal.
Camptodactyly-arthropathy-coxa vara-pericarditis syndrome
Camptodactyly-arthropathy-pericarditis syndrome
Hypertrophic synovitis, congenital familial
Pericarditis-arthropathy-camptodactyly syndrome
An autosomal recessive disorder characterized by the association of congenital or early-onset camptodactyly and non-inflammatory arthropathy with synovial hyperplasia. Individuals with CACP have normal appearing joints at birth but with advancing age develop joint failure, non-inflammatory synoviocyte hyperplasia and subintimal fibrosis of the synovial capsule. Some patients also manifest progressive coxa vara deformity and/or non-inflammatory pericardial or pleural effusions.
An autosomal recessive disorder characterized by hand and foot deformities consisting of polydactyly with digits arising from the dorsum of hands, syn- and camptodactyly of some fingers, soft tissue syndactyly of first and second toes, and dysplastic nails.
An autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision.
Spongy degeneration of central nervous system
A rare neurodegenerative condition of infancy or childhood characterized by white matter vacuolization and demyelination that gives rise to a spongy appearance. The clinical features are onset in early infancy, atonia of neck muscles, hypotonia, hyperextension of legs and flexion of arms, blindness, severe mental defect, megalocephaly, and death by 18 months on the average.
Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma
An autosomal recessive genodermatosis characterized by hypo- and hyperpigmented macular skin lesions, progressive alopecia, palmoplantar keratoderma, dystrophic nails, teeth abnormalities and a predisposition to squamous cell carcinoma.
Candidiasis familial chronic mucocutaneous
A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.
Candidiasis familial chronic mucocutaneous autosomal dominant
Candidiasis familial chronic mucocutaneous autosomal recessive
A disorder characterized by altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.
A rare congenital skeletal muscle disorder characterized by the presence of cap-like structures which are well demarcated and peripherally located under the sarcolemma and show abnormal accumulation of sarcomeric proteins. Clinical features are early onset of hypotonia and slowly progressive muscle weakness. Respiratory problems are common.
A rare congenital skeletal muscle disorder characterized by the presence of cap-like structures which are well demarcated and peripherally located under the sarcolemma and show abnormal accumulation of sarcomeric proteins. Clinical features are early onset of hypotonia and non-progressive or slowly progressive muscle weakness. Respiratory problems are common.
Capillary malformation-arteriovenous malformation 1
A disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. CMAVM1 inheritance is autosomal dominant.
Capillary malformation-arteriovenous malformation 2
An autosomal dominant disorder characterized by multiple, round to oval or more irregularly shaped macules that are pinkish red in color and are randomly distributed across the body. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome.
A form of vascular malformations that are present from birth, tend to grow with the individual, do not regress spontaneously, and show normal rates of endothelial cell turnover. Capillary malformations are distinct from capillary hemangiomas, which are highly proliferative lesions that appear shortly after birth and show rapid growth, slow involution, and endothelial hypercellularity.
Carbamoyl phosphate synthetase 1 deficiency
Carbamoyl phosphate synthetase I deficiency
Hyperammonemia due to carbamoyl phosphate synthetase I deficiency
An autosomal recessive disorder of the urea cycle causing hyperammonemia. It can present as a devastating metabolic disease dominated by severe hyperammonemia in neonates or as a more insidious late-onset condition, generally manifesting as life-threatening hyperammonemic crises under catabolic situations. Clinical features include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and intellectual disability.
Patients affected present some combination of angioedema or chronic urticaria, as well as hay fever or asthma, and have also slightly depressed serum carboxy peptidase N, suggestive of autosomal recessive inheritance of this disorder.
Cardiac arrhythmia syndrome, with or without skeletal muscle weakness
Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness
An autosomal recessive cardiac disorder characterized by stress-induced arrhythmias in infancy or early childhood. Patients present with recurrent syncope or cardiac arrest after physical activity or emotional stress. Sudden death may occur in early childhood. Some patients have muscle weakness.
Cardiac conduction disease with or without dilated cardiomyopathy
A cardiac disorder characterized by atrial tachyarrhythmia and conduction system disease. Some patients have dilated cardiomyopathy.
An autosomal recessive form of congenital heart defects, characterized by valvular malformations involving the pulmonic, tricuspid and mitral valves.
An autosomal recessive form of congenital heart defects, characterized primarily by congenital stenosis and insufficiency of the semilunar valves, although mild insufficiency of the atrioventricular valves has been observed as well. Other features include subaortic stenosis and dilation of the ascending aorta and/or pulmonary artery in some patients.
A rare X-linked heart disease characterized by mitral and/or aortic valve regurgitation. The histologic features include fragmentation of collagenous bundles within the valve fibrosa and accumulation of proteoglycans, which produces excessive valve tissue leading to billowing of the valve leaflets.
Cardiac, facial, and digital anomalies with developmental delay
An autosomal dominant disorder characterized by delayed motor and speech development, developmental regression, congenital heart defects, limb and digital anomalies, and dysmorphic features. Cardiac features include pulmonary stenosis, patent ductus arteriosus, aortic coarctation, valvular defects, hypoplastic left heart, double outlet right ventricle, and conduction abnormalities. Dysmorphic facial features include multiple hair whorls or hairline abnormalities, ptosis, epicanthal folds, and low-set or dysplastic ears.
An autosomal dominant syndrome characterized by partial anomalous pulmonary venous return, tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism.
An autosomal dominant disease characterized by dysmorphic facial features, congenital cardiac defects, primarily common atrium or atrioventricular septal defect, and limb anomalies, including short limbs, brachydactyly and postaxial polydactyly.
An autosomal dominant disease characterized by dysmorphic facial features, congenital cardiac defects, primarily common atrium or atrioventricular septal defect, and limb anomalies, including short limbs, brachydactyly and postaxial polydactyly. CAFD2 patients may show developmental delay of variable severity, intellectual disability, autistic features and focal seizures.
A multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices.
A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. CFC2 patients often do not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma observed in CFC1.
A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures.
A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices.
An autosomal recessive disorder characterized by global developmental delay, feeding difficulties, microcephaly and dysmorphic features. Additional features include cleft lip, cleft palate, variable cardiac defects, and abdominal situs inversus with asplenia. Brain imaging reveals cerebellar hypoplasia.
Cardiomyopathy dilated with conduction defect 1
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Cardiomyopathy, dilated 1AA, with or without left ventricular non-compaction
Cardiomyopathy, dilated 1C, with or without left ventricular non-compaction
Cardiomyopathy dilated with left ventricular noncompaction
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Cardiomyopathy dilated type 1C is associated with left ventricular non-compaction in some patients. Left ventricular non-compaction is characterized by numerous prominent trabeculations and deep intertrabecular recesses in hypertrophied and hypokinetic segments of the left ventricle.
Dilated cardiomyopathy with conduction defect 2
Dilated cardiomyopathy with conduction disorder and arrhythmia
Cardiomyopathy dilated with sensorineural hearing loss autosomal dominant
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD1J is characterized by the association of sensorineural hearing loss and dilated cardiomyopathy in the absence of other anomalies.
Dilated cardiomyopathy with ventricular tachycardia
Dilated cardiomyopathy with mild or no proximal muscle weakness
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2C is an autosomal recessive form with variable severity and age of onset ranging from 2 to 20 years. Death in infancy or early childhood may occur in severely affected children.
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2D is an autosomal recessive, severe form with neonatal onset.
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2E is an autosomal recessive form with neonatal or early childhood onset and rapid progression to cardiac failure.
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2F is an autosomal recessive, early-onset form.
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2G is an autosomal recessive form characterized by early-onset, severe cardiomyopathy that progresses rapidly to heart failure in the neonatal period without evidence of intervening hypertrophy.
A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2H is an autosomal recessive form characterized by rapid progression and death in early infancy.
Cardiomyopathy, dilated, with hypergonadotropic hypogonadism
Cardiomyopathy congestive with hypergonadotropic hypogonadism
Cardiomyopathy dilated with premature ovarian failure
Cardiomyopathy with primary testicular failure
A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including intellectual disability, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia.
Cardiomyopathy, dilated, with woolly hair and keratoderma
Palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair
An autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy.
Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis
A cardiocutaneous syndrome characterized by biventricular dilated cardiomyopathy, hyperkeratosis, woolly hair, palmoplantar keratoderma, and hypo/oligodontia.
Hypertrophic subaortic stenosis, idiopathic
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Cardiomyopathy, familial hypertrophic 10
Familial hypertrophic cardiomyopathy with mid-left ventricular chamber type 2
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. Rarely, patients present a variant of familial hypertrophic cardiomyopathy, characterized by mid-left ventricular chamber thickening.
Cardiomyopathy, familial hypertrophic 11
Cardiomyopathy, familial hypertrophic 12
Cardiomyopathy, familial hypertrophic 13
Cardiomyopathy, familial hypertrophic 14
Cardiomyopathy, familial hypertrophic 15
Cardiomyopathy, familial hypertrophic 16
Cardiomyopathy, familial hypertrophic 17
Cardiomyopathy, familial hypertrophic 18
Cardiomyopathy, familial hypertrophic 20
Cardiomyopathy, familial hypertrophic 22
Cardiomyopathy, familial hypertrophic 23, with or without left ventricular non-compaction
Cardiomyopathy, familial hypertrophic 23, with or without LVNC
Cardiomyopathy, familial hypertrophic 24
Cardiomyopathy, familial hypertrophic 25
Cardiomyopathy, familial hypertrophic 26
Cardiomyopathy, familial hypertrophic 27
A form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH27 is a severe, early-onset form with features of hypertrophic and dilated cardiomyopathy.
Cardiomyopathy, familial hypertrophic 28
A form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH28 is an autosomal dominant form with incomplete penetrance.
Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH6 patients present Wolff-Parkinson-White ventricular preexcitation, enlarged myocytes without myofiber disarray, and glycogen-containing cytosolic vacuoles within cardiomyocytes.
Familial hypertrophic cardiomyopathy with mid-left ventricular chamber type 1
A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function.
A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. RCM6 is an autosomal recessive, severe form characterized by prenatal onset, irreversible heart failure and early death.
A heart disease characterized by the presence of pale granular foamy histiocyte-like cells within the myocardium. It usually affects children younger than 2 years of age, with a clear predominance of females over males. Infants present with dysrhythmia or cardiac arrest. The clinical course is usually fulminant, sometimes simulating sudden infant death syndrome.
An infantile form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Mitral regurgitation, conductive deafness, and fusion of cervical vertebrae and of carpal and tarsal bones
A syndrome characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. CSCF transmission pattern is consistent with autosomal dominant inheritance.
Congenital non-progressive myopathy with Moebius and Robin sequences
Myopathy, congenital nonprogressive, with Moebius sequence and Robin sequence
An autosomal recessive multisystem disorder characterized by hypotonia, bilateral congenital facial palsy with impairment of ocular abduction (Moebius sequence), micrognathia, glossoptosis and high-arched or cleft palate (Pierre Robin complex), delayed motor milestones, and failure to thrive.
An autosomal recessive disorder characterized by weakness of the facial musculature, hypomimic facies, increased overbite, micrognathia, and facial dysmorphism. Some patients manifest failure to thrive, axial hypotonia, and progressive scoliosis.
Myxoma, spotty pigmentation, and endocrine overactivity
CNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas.
Carney complex is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. Familial cardiac myxomas are associated with spotty pigmentation of the skin and other phenotypes, including primary pigmented nodular adrenocortical dysplasia, extracardiac (frequently cutaneous) myxomas, schwannomas, and pituitary, thyroid, testicular, bone, ovarian, and breast tumors. Cardiac myxomas do not develop in all patients with the Carney complex, but affected patients have at least two features of the complex or one feature and a clinically significant family history.
Carnitine palmitoyltransferase 1A deficiency
Carnitine palmitoyltransferase I deficiency
Rare autosomal recessive metabolic disorder of long-chain fatty acid oxidation characterized by severe episodes of hypoketotic hypoglycemia usually occurring after fasting or illness. Onset is in infancy or early childhood.
Carnitine palmitoyltransferase 2 deficiency, infantile
Carnitine palmitoyltransferase II deficiency, hepatocardiomuscular
Carnitine palmitoyltransferase II deficiency with hypoketotic hypoglycemia
An autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation, characterized by hepatic or hepato-cardio-muscular manifestations with onset in infancy. Clinical features include hypoketotic hypoglycemia, lethargy, seizures, hepatomegaly, liver dysfunction, cardiomegaly and dilated cardiomyopathy.
Carnitine palmitoyltransferase 2 deficiency, lethal neonatal
Carnitine palmitoyltransferase II deficiency, antenatal
Carnitine palmitoyltransferase II deficiency, neonatal
An autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation with fatal outcome, presenting shortly after birth. It is characterized by respiratory distress, seizures, altered mental status, hepatomegaly, cardiomegaly, cardiac arrhythmia, and, in many cases, dysmorphic features, renal dysgenesis, and migration defects. recessive.
Carnitine palmitoyltransferase 2 deficiency, myopathic, stress-induced
Carnitine palmitoyltransferase 2 deficiency, late-onset
Carnitine palmitoyltransferase II deficiency, adult-onset
Carnitine palmitoyltransferase II deficiency, myopathic
An autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation, characterized by recurrent myoglobinuria, episodes of muscle pain, stiffness, and rhabdomyolysis. These symptoms are exacerbated by prolonged exercise, fasting, cold, or viral infection. CPT2DM affects most frequently children or young adults, and severity of attacks is highly variable. Myoglobinuria can cause kidney failure and death.
Carnitine-acylcarnitine translocase deficiency
A rare long-chain fatty acid oxidation disorder. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy, arrhythmias, skeletal muscle damage, liver dysfunction and episodes of life-threatening coma, which eventually lead to death. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate.
A condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis.
An autosomal dominant form of carpal tunnel syndrome, a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis.
A rare autosomal recessive disorder characterized by acrocephaly with variable synostosis of the sagittal, lambdoid, and coronal sutures; peculiar facies; brachydactyly of the hands with syndactyly; preaxial polydactyly and syndactyly of the feet; congenital heart defects; growth retardation; intellectual disability; hypogenitalism; and obesity. In addition, cerebral malformations, oral and dental abnormalities, coxa valga, genu valgum, hydronephrosis, precocious puberty, and hearing loss may be observed.
An autosomal recessive multiple congenital malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet, in association with abnormal left-right patterning and other features, most commonly obesity, umbilical hernia, cryptorchidism, and congenital heart disease.
Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.
Cataract 1, multiple types, with or without microcornea
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT1 includes congenital, zonular pulverulent, nuclear progressive, nuclear pulverulent, nuclear total, total, and posterior subcapsular types of cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
Cataract, congenital, zonular with sutural opacities
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT10 includes congenital zonular with sutural opacities, among others. This is a form of zonular cataract with an erect Y-shaped anterior and an inverted Y-shaped posterior sutural opacities. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes.
Cataract 11 with microphthalmia and neurodevelopmental abnormalities
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT11 includes posterior polar cataract, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Some CTRCT11 patients can present a severe phenotype including microphthalmia and neurological dysfunction.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. The opacities can be nuclear, sutural, stellate cortical, lamellar, cortical, nuclear embryonic, Y-sutural, punctate cortical, congenital or with juvenile- and adult-onset.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT13 is associated with the rare adult i phenotype, in which adult red blood cells are rich in i antigen and contain low levels of I antigen.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT14 includes zonular pulverulent cataract, among others. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT15 includes polymorphic, progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical, among others.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT16 includes posterior polar cataract, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens.
Autosomal recessive congenital nuclear cataract 3
Cataract 17, multiple types, with or without microcornea
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT17 includes nuclear and pulverulent cataracts, among others. Nuclear cataracts affect the central nucleus of the eye, are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders. Pulverulent cataracts are characterized by a dust-like, 'pulverised' appearance of the opacities which can be found in any part of the lens.
Autosomal recessive congenital cataract 2
An opacification of the crystalline lens of the eye becoming evident at birth or in infancy. It frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function.
Cataract 2, multiple types, with or without microcornea
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT2 includes Coppock-like cataract, among others. Coppock-like cataract is a congenital pulverulent disk-like opacity involving the embryonic nucleus with many tiny white dots in the lamellar portion of the lens. It is usually bilateral and dominantly inherited. In some cases, CTRCT2 is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT20 includes progressive polymorphic anterior, posterior, or peripheral cortical.
Cataract, pulverulent or cerulean, with or without microcornea
Cataract 21, multiple types, with or without microcornea
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT21 includes cerulean and pulverulent cataracts. Cerulean cataracts are characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Pulverulent cataracts are characterized by a dust-like, 'pulverised' appearance of the opacities which can be found in any part of the lens. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
Autosomal recessive congenital nuclear cataract 2
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT22 includes nuclear cataract among others. Nuclear cataracts affect the central nucleus of the eye, and are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT23 is a zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes.
Sutural cataract with punctate and cerulean opacities
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT3 includes congenital cerulean and sutural cataract with punctate and cerulean opacities, among others. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Sutural cataract with punctate and cerulean opacities is characterized by white opacification around the anterior and posterior Y sutures, and grayish and bluish, spindle shaped, oval punctate and cerulean opacities of various sizes arranged in lamellar form. The spots are more concentrated towards the peripheral layers and do not delineate the embryonal or fetal nucleus. Phenotypic variation with respect to the size and density of the sutural opacities as well as the number and position of punctate and cerulean spots is observed among affected subjects.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT31 includes posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular cataracts.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT33 has juvenile-onset and the opacities are restricted to the cortex of the lens, not involving the nucleus.
Cataract, autosomal recessive congenital 3
Cataract 34, multiple types, with or without microcornea
Autosomal recessive congenital cataract 4
An opacification of the crystalline lens of the eye becoming evident at birth. It frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function.
Autosomal recessive congenital cataract 5
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT39 includes lamellar, anterior polar, and complete cataracts.
Cataract 4, multiple types, with or without microcornea
Congenital non-nuclear polymorphic cataract
Punctate, progressive juvenile-onset, cataract
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT4 includes crystalline aculeiform, congenital cerulean and non-nuclear polymorphic cataracts, among others. Crystalline aculeiform cataract is characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. Non-nuclear polymorphic cataract is a partial opacity with variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Congenital cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract.
Congenital total cataract with posterior sutural opacities in heterozygotes
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT40 manifests as a congenital nuclear opacity with severe visual impairment in affected males. Heterozygous females have suture cataracts and only slight reduction in vision. In some cases, cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive.
Cataract 46, juvenile-onset, with or without arrhythmic cardiomyopathy
A form of cataract, an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT46 can be associated with variable onset of a severe form of arrhythmic cardiomyopathy resulting in sudden cardiac death.
Cataract, juvenile, with microcornea and glucosuria
A form of cataract, an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT47 is characterized by the association of cataract with microcornea and renal glucosuria. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. Renal glucosuria is defined by elevated glucose level in the urine without hyperglycemia and without evidence of morphological renal anomalies.
A form of cataract, an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT48 is an autosomal recessive form characterized by infantile or early-childhood onset.
A form of cataract, an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT49 is an autosomal dominant form characterized by congenital cataract located in the posterior region of the lens. Visual impairment has onset in early childhood.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT5 includes infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type cataracts, among others. Finger malformation is observed in some kindreds.
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age-related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision.
Autosomal recessive congenital cataract 1
Cataract 9, multiple types, with or without microcornea
An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT9 includes nuclear, zonular central nuclear, anterior polar, cortical, embryonal, anterior subcapsular, fan-shaped, and total cataracts, among others. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia
An autosomal recessive disorder characterized by cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, skeletal dysplasia, scoliosis, and facial dysmorphism.
Cataracts, spastic paraparesis, and speech delay
An autosomal dominant disease characterized by bilateral cataracts apparent at birth or in infancy, spastic paraparesis, truncal hypotonia, delayed psychomotor development, and speech delay.
Hyperphalangy-clinodactyly of index finger with Pierre Robin syndrome
Index finger anomaly with Pierre Robin syndrome
Palatodigital syndrome, Catel-Manzke type
Pierre Robin syndrome with hyperphalangy and clinodactyly
A syndrome characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia).
Cleft lip, cataract, tooth abnormality, intellectual disability, facial dysmorphism, attention-deficit hyperactivity disorder
An autosomal recessive disorder characterized by global developmental delay, intellectual disability, and behavioral abnormalities with mild to severe attention-deficit hyperactivity disorder. Motor, speech and cognitive deficits range from mild to severe. Patients show craniofacial dysmorphism including elongated face, short, broad upturned nose with anteverted nares and long philtrum. Additional clinical features are cleft lip/palate, tooth abnormalities, and visual impairment due to cataract, strabismus and poor visual tracking.
A condition characterized by the occurrence of duplications of different organs in the caudal region.
An ocular disease characterized by a profound excavation of the optic nerve. Clinical phenotype is variable and includes congenitally excavated optic nerves as well as other features of optic pit, optic nerve coloboma, and morning glory disk anomaly. Patients with CODA have a strong predilection for retinal detachment and/or separation of the retinal layers (retinoschisis) that lead to profound central vision loss.
An immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.
Craniofacial defects, dysmorphic ears, structural brain abnormalities, expressive language delay, and impaired intellectual development
An autosomal dominant developmental disorder characterized by global developmental delay, intellectual disability with severe expressive language delay, craniofacial dysmorphism, and structural brain abnormalities. Most patients have an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres. Other frequent features include perisylvian polymicrogyria, abnormal posterior clinoid processes, cerebellar hypoplasia or dysplasia, and persistent trigeminal artery.
A multifactorial, chronic disorder of the small intestine caused by intolerance to gluten. It is characterized by immune-mediated enteropathy associated with failed intestinal absorption, and malnutrition. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes.
A congenital malformation syndrome defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. It is characterized by fusion and disorganization of metacarpal and phalangeal bones, radius and ulnar shortening, radioulnar synostosis, and severe syndactyly of hands and feet.
Autosomal dominant congenital myopathy, but a severe autosomal recessive form also exists. Both clinical and histological variability is observed. Affected individuals typically display hypotonia and proximal muscle weakness in infancy, leading to the delay of motor milestones. The clinical course of the disorder is usually slow or nonprogressive in adulthood, and the severity of the symptoms may vary from normal to significant muscle weakness. Microscopic examination of CCD-affected skeletal muscle reveals a predominance of type I fibers containing amorphous-looking areas (cores) that do not stain with oxidative and phosphorylase histochemical techniques.
Central hypoventilation syndrome, congenital, 1
Central hypoventilation syndrome, congenital
An autosomal dominant form of congenital central hypoventilation syndrome, a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction
An autosomal recessive form of congenital central hypoventilation syndrome, a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular, lung or cardiac disease, or an identifiable brainstem lesion. CCHS2 is characterized by shallow breathing and apneic spells apparent in the neonatal period. Some patients have other features of autonomic dysfunction, including bladder dysfunction, sinus bradycardia, and temperature dysregulation.
Central hypoventilation syndrome, congenital, 3
A form of congenital central hypoventilation syndrome, a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular, lung or cardiac disease, or an identifiable brainstem lesion. CCHS3 is an autosomal recessive, neonatal form characterized by slow and shallow breathing due to a deficiency in autonomic control of respiration. Affected individuals present with respiratory insufficiency and absence of the hypercapnic reflex that stimulates breathing. Additional features include gastrointestinal problems, poor heat tolerance and paroxysmal hypertension.
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss
An autosomal dominant neurologic disorder characterized by relapsing and partially remitting, early-onset cerebellar ataxia following a febrile illness. Other features include progressive optic atrophy and sensorineural hearing loss, generalized hypotonia, areflexia and pes cavus without evidence of a peripheral neuropathy on neurophysiological studies.
Cerebellar ataxia, brain abnormalities, and cardiac conduction defects
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development and speech delay that are observed in most patients. Disease manifestations are variable and include infantile-onset hypotonia, poor motor development, poor feeding and overall growth, and ataxic gait due to cerebellar ataxia. Additional variable features are dysarthria, nystagmus, variable ocular anomalies, spasticity, hyperreflexia, and non-specific dysmorphic features. Brain imaging shows cerebellar hypoplasia, often with brainstem hypoplasia, enlarged ventricles, delayed myelination, and thin corpus callosum. A significant number of patients develop cardiac conduction defects in childhood or adolescence.
Found in a population isolate on Grand Cayman Island and causes a marked psychomotor retardation and prominent nonprogressive cerebellar dysfunction including nystagmus, intention tremor, dysarthria, and wide-based ataxic gait. Hypotonia is present from early childhood.
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant
An autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy, cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression.
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 1
An autosomal recessive, congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, intellectual disability, cerebellar hypoplasia and mild cerebral gyral simplification. Additional features include short stature, strabismus, pes planus and, rarely, seizures.
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 2
An autosomal recessive, congenital cerebellar ataxia associated with cerebellar hypoplasia, intellectual disability, and inability to walk bipedally, resulting in quadrupedal locomotion as a functional adaptation. Additional findings include generalized brain atrophy and mild hypoplasia of the corpus callosum.
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 3
An autosomal recessive, congenital cerebellar ataxia associated with dysarthia, quadrupedal gait and intellectual disability.
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome
An autosomal recessive neurologic disease characterized by imbalance, cerebellar ataxia, impaired vestibular function, and non-length-dependent sensory deficit.
Cerebellar atrophy with seizures and variable developmental delay
An autosomal recessive neurologic disorder characterized by cerebellar ataxia, atrophy of the cerebellar vermis, severe refractory seizures with early onset, and global developmental delay compatible with epileptic encephalopathy in most patients. Disease severity is variable and normal cognitive development has also been reported.
Cerebellar atrophy, developmental delay, and seizures
An autosomal recessive disease characterized by epilepsy, developmental delay and severe cerebellar atrophy.
Cerebellar atrophy, visual impairment, and psychomotor retardation
An autosomal recessive, neurodegenerative disorder characterized by developmental delay, intellectual disability, hypotonia, scoliosis, cerebellar atrophy, and variable dysmorphic features.
Cerebellar dysfunction with variable cognitive and behavioral abnormalities
An autosomal dominant neurodevelopmental disorder characterized by mildly delayed psychomotor development, early onset of cerebellar ataxia, and intellectual disability later in childhood and adult life. Other features may include neonatal hypotonia, dysarthria, and dysmetria. Brain imaging in some patients shows cerebellar atrophy. Dysmorphic facial features are variable.
Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism
An autosomal recessive disorder characterized by delayed motor development, ataxia with cerebellar hypoplasia, severe progressive scoliosis, moderate to severe intellectual disability, and delayed puberty with congenital hypogonadotropic hypogonadism.
Cerebellar hypoplasia/atrophy, epilepsy, and global developmental delay
An autosomal recessive neurodevelopmental disorder characterized by infantile onset of hypotonia, global developmental delay, delayed walking, and severely impaired intellectual development with profound speech delay. Patients manifest cerebellar atrophy and childhood-onset epilepsy.
Cerebellar, ocular, craniofacial, and genital syndrome
An autosomal recessive syndrome characterized by moderate to severe developmental delay, intellectual disability, cerebellar hypoplasia with ataxia, variable microcephaly, ophthalmological anomalies, facial dysmorphism, absent or underdeveloped nipples, underdeveloped labioscrotal folds and scrotal agenesis.
An autosomal recessive disorder characterized by cerebellar hypoplasia, delayed development and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies.
Cerebral amyloid angiopathy, APP-related
Amyloidosis hereditary with cerebral hemorrhage Dutch variant
Cerebral amyloid angiopathy APP-related Arctic variant
Cerebral amyloid angiopathy APP-related Dutch variant
Cerebral amyloid angiopathy APP-related Flemish variant
Cerebral amyloid angiopathy APP-related Iowa variant
Cerebral amyloid angiopathy APP-related Italian variant
Familial occipital calcifications with hemorrhagic strokes leukoencephalopathy arterial dysplasia dementia
Hereditary cerebral amyloid angiopathy Dutch type
Hereditary cerebral hemorrhage with amyloidosis Dutch type
Hereditary cerebral hemorrhage with amyloidosis Italian type
A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.
Cerebral amyloid angiopathy, ITM2B-related 1
Cerebral amyloid angiopathy British type
A disorder characterized by amyloid deposition in the walls of cerebral blood vessels and neurodegeneration in the central nervous system. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Clinical features include progressive mental deterioration, spasticity and muscular rigidity.
Cerebral amyloid angiopathy, ITM2B-related 2
Cerebellar ataxia cataract deafness and dementia or psychosis
A disorder characterized by amyloid deposition in the walls of the blood vessels of the cerebrum, choroid plexus, cerebellum, spinal cord and retina. Plaques and neurofibrillary tangles are observed in the hippocampus. Clinical features include progressive ataxia, dementia, cataracts and deafness.
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 1
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant
A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke.
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 2
Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, autosomal dominant, 2
Cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy
Cerebrovascular disease with thin skin, alopecia, and disk disease
Progressive subcortical vascular encephalopathy
Subcortical vascular encephalopathy, progressive
A cerebrovascular disease characterized by non-hypertensive arteriopathy of cerebral small vessels with subcortical infarcts, alopecia, and spondylosis. Small cerebral arteries show arteriosclerotic changes, fibrous intimal proliferation, and hyaline degeneration with splitting of the intima and/or the internal elastic membrane. Neurologic features include progressive dementia, gait disturbances, extrapyramidal and pyramidal signs, and demyelination of the cerebral white matter with sparing of U fibers.
A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM1 inheritance is autosomal dominant.
A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM2 inheritance is autosomal dominant.
A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM3 inheritance is autosomal dominant.
A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM4 cases occur sporadically.
An X-linked disorder of creatine transport characterized by intellectual disability, severe speech delay, behavioral abnormalities, and seizures. Carrier females may show mild neuropsychologic impairment.
Creatine deficiency syndrome due to GAMT deficiency
Guanidinoacetate methyltransferase deficiency
An autosomal recessive disorder characterized by developmental delay and regression, intellectual disability, severe disturbance of expressive and cognitive speech, intractable seizures, movement disturbances, severe depletion of creatine and phosphocreatine in the brain, and accumulation of guanidinoacetic acid in brain and body fluids.
Arginine:glycine amidinotransferase deficiency
Creatine deficiency syndrome due to AGAT deficiency
An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life.
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome
A neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis and palmoplantar keratoderma.
Autosomal recessive symmetric spastic cerebral palsy 1
A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest symmetrical, non-progressive spasticity and no adverse perinatal history or obvious underlying alternative diagnosis. Developmental delay, intellectual disability and sometimes epilepsy can be part of the clinical picture.
A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest congenital hypotonia evolving over the first year to spastic quadriplegia with accompanying transient nystagmus and varying degrees of intellectual disability. Neuroimaging shows brain atrophy and ventriculomegaly.
A form of cerebral palsy, a group of non-progressive disorders of movement and/or posture resulting from defects in the developing central nervous system. CPSQ3 is an autosomal recessive neurodevelopmental disorder characterized by variable spasticity and cognitive impairment.
A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.
A syndrome characterized by severe micrognathia, rib defects ranging from a few dorsal rib segments to complete absence of ossification, and intellectual disability.
Cerebroretinal microangiopathy with calcifications and cysts 1
An autosomal recessive pleiomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anemia and thrombocytopenia.
Cerebroretinal microangiopathy with calcifications and cysts 2
An autosomal recessive, multisystemic disorder characterized by intrauterine growth retardation and, later in life, premature aging symptoms, including poor growth, graying hair, liver fibrosis, portal hypertension, esophageal varices, osteopenia, pancytopenia, hypocellular bone marrow, and vascular telangiectasia resulting in gastrointestinal bleeding. Brain calcifications and white matter changes are responsible for signs including spasticity, ataxia, or dystonia observed in some patients.
Rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts.
Infantile neuronal ceroid lipofuscinosis
Juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits
Neuronal ceroid lipofuscinosis with variable age at onset
A form of neuronal ceroid lipofuscinosis with variable age at onset. Infantile, late-infantile, juvenile, and adult onset have been reported. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD).
Congenital neuronal ceroid lipofuscinosis
Neuronal ceroid lipofuscinosis cathepsin d-deficient
Neuronal ceroid lipofuscinosis due to cathepsin D deficiency
A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.
A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.
Ceroid lipofuscinosis, neuronal, 13 (Kufs type)
Neuronal ceroid lipofuscinosis 13 Kufs type
A form of neuronal ceroid lipofuscinosis characterized by adult onset of progressive cognitive decline and motor dysfunction leading to dementia and often early death. Some patients develop seizures. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material. CLN13 inheritance is autosomal recessive.
Late-infantile neuronal ceroid lipofuscinosis
Neuronal ceroid lipofuscinosis 2 with variable age at onset
A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.
A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a fingerprint profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with neuronal ceroid lipofuscinosis type 3.
Ceroid lipofuscinosis, neuronal, 4A (Kufs type), autosomal recessive
An adult-onset neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. CLN4A has no visual involvement and is characterized by progressive myoclonic epilepsy.
Ceroid lipofuscinosis, neuronal, 4B (Kufs type), autosomal dominant
Neuronal ceroid lipofuscinosis Parry type
An adult-onset neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. CLN4B has no visual involvement and is characterized by seizures and other neurologic symptoms.
Finnish variant late infantile neuronal ceroid lipofuscinosis
Neuronal ceroid lipofuscinosis 5 with variable age at onset
A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 5 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
Neuronal ceroid lipofuscinosis 6 with variable age at onset
Variant late-onset infantile neuronal ceroid lipofuscinosis
An autosomal recessive form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 6 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
A form of neuronal ceroid lipofuscinosis with onset in early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 7 comprise mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles.
A form of neuronal ceroid lipofuscinosis with onset in childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 8 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant
A form of neuronal ceroid lipofuscinosis clinically characterized by epilepsy that presents between 5 and 10 years of age with frequent tonic-clonic seizures followed by progressive intellectual disability. Visual loss is not a prominent feature. Intracellular accumulation of autofluorescent material results in curvilinear and granular profiles on ultrastructural analysis.
A malignant neoplasm of the cervix, typically originating from a dysplastic or premalignant lesion previously present at the active squamocolumnar junction. The transformation from mild dysplastic to invasive carcinoma generally occurs slowly within several years, although the rate of this process varies widely. Carcinoma in situ is particularly known to precede invasive cervical cancer in most cases. Cervical cancer is strongly associated with infection by oncogenic types of human papillomavirus.
A progressive disease characterized by glomerulonephritis, hematuria, renal failure, end-stage renal disease, subendothelial and mesangial glomerular C3 deposits, mesangial matrix expansion, increased glomerular cellularity, and segmental capillary wall thickening. Hematuria may become apparent after respiratory infections.
Ichthyosiform erythroderma with leukocyte vacuolation
Ichthyotic neutral lipid storage disease
Neutral lipid storage disease with ichthyosis
Triglyceride storage disease with impaired long-chain fatty acid oxidation
An autosomal recessive inborn error of lipid metabolism with multisystemic accumulation of triglycerides although plasma concentrations are normal. Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. The disorder presents at birth with generalized, fine, white scaling of the skin and a variable degree of erythema resembling non-bullous congenital ichthyosiform erythroderma.
Curly hair, ankyloblepharon, nail dysplasia syndrome
An autosomal recessive syndrome characterized by ankyloblepharon, sparse, curly and woolly hair, nail dysplasia, and oral frenula.
An autosomal dominant disorder characterized by patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies.
Charcot-Marie-Tooth disease demyelinating autosomal recessive, type 4A
Charcot-Marie-Tooth disease neuropathy type 4A
A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4A is a severe form characterized by early age of onset and rapid progression leading to inability to walk in late childhood or adolescence.
Charcot-Marie-Tooth disease autosomal recessive with focally folded myelin sheaths 4B1
Charcot-Marie-Tooth disease demyelinating autosomal recessive 4B1
A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4.
Charcot-Marie-Tooth disease autosomal recessive with focally folded myelin sheaths 4B2
Charcot-Marie-Tooth disease demyelinating autosomal recessive 4B2
Charcot-Marie-Tooth disease demyelinating autosomal recessive 4C
A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4C is characterized by onset in childhood, early-onset scoliosis and a distinct Schwann cell pathology.
Charcot-Marie-Tooth disease demyelinating autosomal recessive 4D
Hereditary motor and sensory neuropathy IVD
Hereditary motor and sensory neuropathy Lom type
Charcot-Marie-Tooth disease demyelinating autosomal recessive 4F
A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4F is characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome.
Charcot-Marie-Tooth disease demyelinating autosomal recessive 4H
Charcot-Marie-Tooth disease, demyelinating, autosomal recessive, type 4K
Charcot-Marie-Tooth disease, demyelinating, type 4K
Charcot-Marie-Tooth neuropathy, demyelinating, autosomal recessive, type 4K
An autosomal recessive, demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4K patients manifest upper and lower limbs involvement. Some affected individuals have nystagmus and late-onset cerebellar ataxia.
Charcot-Marie-Tooth disease, axonal, 2A1
Charcot-Marie-Tooth disease axonal type 2A1
Charcot-Marie-Tooth disease neuronal type 2A1
Hereditary motor and sensory neuropathy IIA1
A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
Charcot-Marie-Tooth disease, axonal, 2A2A
Charcot-Marie-Tooth disease axonal type 2A2
Charcot-Marie-Tooth disease neuronal type 2A2
Hereditary motor and sensory neuropathy IIA2
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
Charcot-Marie-Tooth disease, axonal, 2A2B
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2A2B
Charcot-Marie-Tooth disease, axonal, type 2A2B
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2A2B is a severe form with autosomal recessive inheritance.
Charcot-Marie-Tooth disease axonal type 2B
Charcot-Marie-Tooth disease neuronal type 2B
Hereditary motor and sensory neuropathy IIB
Peripheral sensory neuropathy autosomal dominant
Charcot-Marie-Tooth disease, axonal, 2B1
Charcot-Marie-Tooth disease axonal autosomal recessive B1
Charcot-Marie-Tooth disease axonal type 2B1
Charcot-Marie-Tooth disease neuronal type 2B1
A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
Charcot-Marie-Tooth disease, axonal, 2B2
Charcot-Marie-Tooth disease axonal autosomal recessive B2
Charcot-Marie-Tooth disease axonal type 2B2
Charcot-Marie-Tooth disease neuronal type 2B2
Charcot-Marie-Tooth disease axonal autosomal dominant 2C
Charcot-Marie-Tooth disease axonal type 2C
Hereditary motor and sensory neuropathy type IIC
Charcot-Marie-Tooth disease, axonal, 2CC
Charcot-Marie-Tooth disease, axonal, type 2CC
Charcot-Marie-Tooth neuropathy, type 2CC
Charcot-Marie-Tooth disease axonal type 2D
Charcot-Marie-Tooth disease neuronal type 2D
Charcot-Marie-Tooth disease, axonal, 2DD
Charcot-Marie-Tooth disease, axonal, type 2DD
Charcot-Marie-Tooth neuropathy, type 2DD
Charcot-Marie-Tooth disease axonal type 2E
Charcot-Marie-Tooth disease neuronal type 2E
Charcot-Marie-Tooth disease, axonal, 2EE
Charcot-Marie-Tooth disease, axonal, type 2EE
Charcot-Marie-Tooth neuropathy, type 2EE
A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2EE is a slowly progressive, sensorimotor peripheral axonal neuropathy with onset in the first or second decades of life. The disorder primarily affects the lower limbs, sometimes resulting in loss of ambulation, with later onset of upper limb involvement.
Charcot-Marie-Tooth disease axonal type 2F
Charcot-Marie-Tooth disease neuronal type 2F
A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Onset of Charcot-Marie-Tooth disease type 2F is between 15 and 25 years with muscle weakness and atrophy usually beginning in feet and legs (peroneal distribution). Upper limb involvement occurs later.
Charcot-Marie-Tooth disease, axonal, 2FF
Charcot-Marie-Tooth disease, axonal, type 2FF
Charcot-Marie-Tooth neuropathy, type 2FF
A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2FF is characterized by early-childhood onset of difficulties walking or running due to atrophy and weakness of the lower limbs. Some patients lose independent ambulation. There is also prominent involvement of the upper limbs.
Charcot-Marie-Tooth disease, axonal, 2HH
Charcot-Marie-Tooth disease, axonal, type 2HH
Charcot-Marie-Tooth neuropathy, type 2HH
An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2HH is characterized by vocal fold paresis that remains throughout life and may be severe. Additional features include pes cavus, scoliosis, distal sensory impairment with hyporeflexia, mild distal muscle weakness and atrophy primarily affecting the lower limbs, although the upper limbs may also be involved.
Charcot-Marie-Tooth disease axonal type 2I
Charcot-Marie-Tooth disease neuronal type 2I
Charcot-Marie-Tooth disease, axonal, 2II
Charcot-Marie-Tooth disease, axonal, type 2II
Charcot-Marie-Tooth neuropathy, type 2II
Charcot-Marie-Tooth disease axonal type 2J
Charcot-Marie-Tooth disease neuronal type 2J
Charcot-Marie-Tooth disease type 2 with hearing loss and pupillary abnormalities
A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Charcot-Marie-Tooth disease type 2J is characterized by the association of axonal peripheral neuropathy with hearing loss and pupillary abnormalities such as Adie pupil.
Charcot-Marie-Tooth disease axonal type 2K
Charcot-Marie-Tooth disease neuronal type 2K
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Charcot-Marie-Tooth disease type 2K onset is in early childhood (younger than 3 years). This phenotype is characterized by foot deformities, kyphoscoliosis, distal limb muscle weakness and atrophy, areflexia, and diminished sensation in the lower limbs. Weakness in the upper limbs is observed in the first decade, with clawing of the fingers. Inheritance can be autosomal dominant or recessive.
Charcot-Marie-Tooth disease axonal autosomal dominant type 2L
Charcot-Marie-Tooth disease axonal type 2L
Charcot-Marie-Tooth disease neuronal type 2L
Charcot-Marie-Tooth disease axonal autosomal dominant type 2M
Charcot-Marie-Tooth disease axonal type 2M
Charcot-Marie-Tooth neuropathy axonal type 2M
Charcot-Marie-Tooth disease axonal autosomal dominant type 2N
Charcot-Marie-Tooth disease axonal type 2N
Charcot-Marie-Tooth neuropathy axonal type 2N
Charcot-Marie-Tooth disease axonal autosomal dominant type 2O
Charcot-Marie-Tooth disease axonal type 2O
Charcot-Marie-Tooth neuropathy axonal type 2O
Charcot-Marie-Tooth disease, axonal type 2G
Charcot-Marie-Tooth disease axonal type 2P
Charcot-Marie-Tooth neuropathy axonal type 2P
Charcot-Marie-Tooth disease axonal autosomal dominant type 2Q
Charcot-Marie-Tooth disease axonal type 2Q
Charcot-Marie-Tooth neuropathy axonal type 2Q
Autosomal recessive Charcot-Marie-Tooth disease axonal type 2R
Charcot-Marie-Tooth disease axonal type 2R
Charcot-Marie-Tooth neuropathy axonal type 2R
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2S
Charcot-Marie-Tooth neuropathy axonal type 2S
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2T.
Charcot-Marie-Tooth neuropathy, type 2T.
Charcot-Marie-Tooth neuropathy axonal type 2T.
Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2U
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2U is a slowly progressive, autosomal dominant form characterized by late-adult onset.
Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2V
Charcot-Marie-Tooth disease, axonal, type 2V
An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2V is an autosomal dominant sensory neuropathy with late onset. The main clinical feature is recurrent leg pain that progresses to constant painful paraesthesias in the feet and later the hands. As it evolves, some patients develop a mild sensory ataxia.
Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2W
Charcot-Marie-Tooth disease, axonal, type 2W
An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement.
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2X
Charcot-Marie-Tooth disease, axonal, type 2X
An autosomal recessive, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2X patients manifest a slowly progressive, peripheral neuropathy affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Some patients also have upper limb involvement.
Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2Y
Charcot-Marie-Tooth disease, axonal, type 2Y
An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2Z
Charcot-Marie-Tooth disease, axonal, type 2Z
Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive
Charcot-Marie-Tooth neuropathy axonal with vocal cord paresis autosomal recessive
CMT2 with vocal cord paresis autosomal recessive
A form of Charcot-Marie-Tooth disease characterized by the association of axonal neuropathy with vocal cord paresis. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms.
Charcot-Marie-Tooth disease, demyelinating, 1A
Charcot-Marie-Tooth disease demyelinating type 1A
Charcot-Marie-Tooth disease slow nerve conduction type unlinked to Duffy
Hereditary motor and sensory neuropathy IA
A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
Charcot-Marie-Tooth disease, demyelinating, 1B
Charcot-Marie-Tooth disease demyelinating type 1B
Charcot-Marie-Tooth disease slow nerve conduction type linked to Duffy
Hereditary motor and sensory neuropathy IB
Charcot-Marie-Tooth disease, demyelinating, 1C
Charcot-Marie-Tooth disease demyelinating type 1C
Hereditary motor and sensory neuropathy IC
Charcot-Marie-Tooth disease, demyelinating, 1D
Charcot-Marie-Tooth disease demyelinating type 1D
Hereditary motor and sensory neuropathy ID
Charcot-Marie-Tooth disease, demyelinating, 1E
Charcot-Marie-Tooth disease and deafness autosomal dominant
Charcot-Marie-Tooth disease demyelinating type 1E
An autosomal dominant form of Charcot-Marie-Tooth disease characterized by the association of sensorineural hearing loss with peripheral demyelinating neuropathy.
Charcot-Marie-Tooth disease, demyelinating, 1F
Charcot-Marie-Tooth disease demyelinating type 1F
A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1F is characterized by onset in infancy or childhood (range 1 to 13 years).
Charcot-Marie-Tooth disease, demyelinating, 1G
Charcot-Marie-Tooth disease, demyelinating, type 1G
An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1G is characterized by distal muscle weakness and atrophy with onset in the first or second decade.
Charcot-Marie-Tooth disease, demyelinating, 1H
Charcot-Marie-Tooth disease, demyelinating, type 1H
Hereditary motor and sensory neuropathy, IH
Neuropathy, hereditary, with or without age-related macular degeneration
An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1H is characterized by peripheral sensorimotor neuropathy with onset usually in adulthood. Affected individuals present with foot deformities, upper or lower limb sensory disturbances, and motor deficits, mainly impaired gait. Rare patients may have hyperelastic skin or develop age-related macular degeneration.
Charcot-Marie-Tooth disease, demyelinating, 1I
Charcot-Marie-Tooth disease, demyelinating, type 1I
An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1I is characterized predominantly by delayed motor development in the first years of life associated with gait abnormalities, sensory ataxia, hyporeflexia, and distal sensory impairment due to a sensorimotor peripheral neuropathy that mainly affects the lower limbs. The disorder is progressive, and some may have upper limb involvement. A subset of patients has central nervous system involvement that manifests as global developmental delay with impaired intellectual development and speech difficulties.
Charcot-Marie-Tooth disease, demyelinating, 1J
Charcot-Marie-Tooth disease, demyelinating, type 1J
An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
Charcot-Marie-Tooth disease, dominant intermediate B
Charcot-Marie-Tooth neuropathy dominant intermediate B
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type B is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, dominant intermediate C
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type C is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, dominant intermediate D
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type D is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, dominant intermediate E
Charcot-Marie-Tooth neuropathy with focal segmental glomerulonephritis
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. The dominant intermediate type E is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. Patients additionally manifest focal segmental glomerulonephritis, proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy.
Charcot-Marie-Tooth disease, dominant intermediate F
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. CMTDIF is characterized by onset around adolescence of slowly progressive distal muscle atrophy and weakness affecting the upper and lower limbs and resulting in steppage gait. There is distal sensory impairment with decreased reflexes. Nerve conduction velocities are variable, ranging from the demyelinating to the axonal range.
Charcot-Marie-Tooth disease, dominant intermediate G
Charcot-Marie-Tooth disease, dominant, intermediate type, G
An autosomal dominant, intermediate form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Dominant intermediate forms are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. CMTDIG is phenotypically variable. Most affected individuals have onset in the first or second decades of slowly progressive distal motor weakness and atrophy, resulting in gait instability and distal upper limb impairment, as well as distal sensory impairment.
Charcot-Marie-Tooth disease, recessive intermediate A
Charcot-Marie-Tooth neuropathy recessive intermediate A
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Charcot-Marie-Tooth disease, recessive intermediate B
Charcot-Marie-Tooth neuropathy recessive intermediate B
Charcot-Marie-Tooth disease, recessive intermediate C
Charcot-Marie-Tooth neuropathy recessive intermediate C
Charcot-Marie-Tooth disease, recessive intermediate D
Charcot-Marie-Tooth disease, X-linked dominant, 1
Charcot-Marie-Tooth neuropathy X-linked 1
Charcot-Marie-Tooth peroneal muscular atrophy X-linked
Hereditary motor and sensory neuropathy X-linked
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. CMTX1 has both demyelinating and axonal features. Central nervous system involvement may occur.
Charcot-Marie-Tooth disease, X-linked dominant, 6
Charcot-Marie-Tooth neuropathy X-linked 6
A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy.
Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia
Charcot-Marie-Tooth disease X-linked recessive 4
A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood.
Charcot-Marie-Tooth disease, X-linked recessive, 5
Charcot-Marie-Tooth neuropathy X-linked recessive 5
Optic atrophy with polyneuropathy and deafness
Common cause of congenital anomalies. Is characterized by a non-random pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina.
A rare autosomal recessive disorder characterized by hypopigmentation, severe immunologic deficiency, a bleeding tendency, neurologic abnormalities, abnormal intracellular transport to and from the lysosome, and giant inclusion bodies in a variety of cell types. Most patients die at an early age unless they receive an allogeneic hematopoietic stem cell transplant (SCT).
An autosomal dominant syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.
A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure.
Congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.
Chilton-Okur-Chung neurodevelopmental syndrome
A disorder characterized by developmental delay, intellectual disability, hypotonia, and structural brain abnormalities including cerebellar vermis hypoplasia and agenesis or hypoplasia of the corpus callosum. Most patients have behavioral abnormalities, including autism spectrum disorder, attention deficit and hyperactivity disorder, and aggression. About half of patients have dysmorphic facial features. Rare involvement of other organ systems may be present.
An autosomal dominant syndrome characterized by hyperphalangism, partial syndactyly, bilateral accessory phalanx resulting in shortened index fingers, hallux valgus, brachydactyly, facial anomalies, diffuse bronchomalacia, and respiratory distress at birth and in infancy.
A disease characterized by posterior choanal atresia and lymphedema. Additional features are a high-arched palate, hypoplastic nipples, and mild pectus excavatum.
Cholestasis of pregnancy, intrahepatic 1
Recurrent intrahepatic cholestasis of pregnancy
A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP1 causes fetal distress, spontaneous premature delivery and intrauterine death. ICP1 patients have spontaneous and progressive disappearance of cholestasis after delivery.
Cholestasis of pregnancy, intrahepatic 3
A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine.
Cholestasis, benign recurrent intrahepatic, 1
Recurrent familial intrahepatic cholestasis
A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically.
Cholestasis, benign recurrent intrahepatic, 2
Cholestasis, neonatal intrahepatic, caused by citrin deficiency
Citrullinemia, type II, neonatal-onset, with or without failure to thrive and dyslipidemia
A form of citrullinemia type 2 with neonatal onset, characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. Neonatal intrahepatic cholestasis due to citrin deficiency is generally not severe and symptoms disappear by one year of age with an appropriate diet. Years or even decades later, however, some individuals develop the characteristic features of citrullinemia type 2 with neuropsychiatric symptoms.
Cholestasis, progressive familial intrahepatic, 1
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC1 inheritance is autosomal recessive.
Cholestasis, progressive familial intrahepatic, 10
A form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC10 is an autosomal recessive form with highly variable phenotype and severity, manifesting in the first months or years of life.
Cholestasis, progressive familial intrahepatic, 11
An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease.
Cholestasis, progressive familial intrahepatic, 12
A form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC12 is an autosomal recessive form characterized by neonatal-onset jaundice and conjugated hyperbilirubinemia, associated with intense pruritus.
Cholestasis, progressive familial intrahepatic, 2
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC2 inheritance is autosomal recessive.
Cholestasis, progressive familial intrahepatic, 3
Progressive familial intrahepatic cholestasis with elevated serum gamma-glutamyltransferase
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC3 inheritance is autosomal recessive.
Cholestasis, progressive familial intrahepatic, 4
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC4 inheritance is autosomal recessive.
Cholestasis, progressive familial intrahepatic, 5
A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period.
Cholestasis, progressive familial intrahepatic, 6
An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC6 patients have elevated liver transaminases and congenital diarrhea.
Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss
An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. Some PFIC7 patients develop hearing loss in childhood.
Cholestasis, progressive familial intrahepatic, 8
An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC8 onset is in early infancy.
Cholestasis, progressive familial intrahepatic, 9
An autosomal recessive form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC9 onset is in infancy or early childhood.
A mild manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. It is characterized by late-onset.
Calcium pyrophosphate dihydrate deposition disease
Calcium pyrophosphate dihydrate deposition disease 2
Chondrocalcinosis is a common cause of joint pain and arthritis caused by calcium deposition in articular cartilage and the presence of calcium hypophosphate crystals in synovial fluid, cartilage and periarticular soft tissue. CCAL2 inheritance is autosomal dominant.
Chondrodysplasia punctata 1, X-linked recessive
Chondrodysplasia punctata brachytelephalangic
A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. CDPX1 is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. This disease can also be induced by inhibition with the drug warfarin.
Chondrodysplasia punctata 2, X-linked dominant
A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-8(9)-en-3-beta-ol in the plasma and tissues.
Chondrodysplasia with joint dislocations, GPAPP type
A condition consisting of congenital joint dislocations, chondrodysplasia with short stature, micrognathia and cleft palate, and a distinctive face.
Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia
A disease characterized by chondrodysplasia, severe platyspondyly, hydrocephaly, and facial features with microphthalmia. Bone abnormalities include a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. Affected females show a milder phenotype with small stature, sometimes associated with body asymmetry and mild intellectual disability.
A malignant neoplasm derived from cartilage cells. Chondrosarcomas range from slow-growing non-metastasizing lesions to highly aggressive metastasizing sarcomas.
An autosomal dominant disorder characterized by developmental delay, intellectual disability, speech delay, and dysmorphic facial features. Additional features include growth failure, feeding difficulties, non-specific brain abnormalities, ophthalmological abnormalities, gait and balance disturbance, joint hypermobility, and predisposition to recurrent infections.
A syndrome characterized by cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia.
Rare, clinically malignant tumors derived from notochordal remnants. They occur along the length of the spinal axis, predominantly in the sphenooccipital, vertebral and sacrococcygeal regions. They are characterized by slow growth, local destruction of bone, extension into adjacent soft tissues and rarely, distant metastatic spread.
Chorea, childhood-onset, with psychomotor retardation
An autosomal recessive neurodevelopmental disorder characterized by abnormal involuntary movements, marked speech delay, intellectual disability and learning difficulties.
A rare autosomal dominant movement disorder, defined by early onset in childhood, a stable or non-progressive course of chorea, and no mental deterioration. Chorea is characterized by involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement.
An autosomal recessive neurodegenerative disorder characterized by the gradual onset of hyperkinetic movements and abnormal erythrocyte morphology. Basal ganglia atrophy in the brain is a pathological feature of the disease. Other clinical symptoms include psychiatric features, epilepsy, peripheral neuropathy, myopathy and oral self-mutilation.
Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction
Choreoathetosis, hypothyroidism, and neonatal respiratory distress
An autosomal dominant disorder that manifests in infancy with neurological disturbances, hypothyroidism, and respiratory problems. It is characterized by movement abnormalities beginning with muscular hypotonia followed by the development of chorea, athetosis, dystonia, ataxia, and dysarthria.
Chorioretinal atrophy, progressive bifocal
Progressive bifocal chorioretinal atrophy
An autosomal dominant, progressive chorioretinal dystrophy characterized by atrophic macular and nasal retinal lesions evident soon after birth, nystagmus, myopia, and poor vision. Retinal detachment is observed in some patients.
A form of central areolar choroidal dystrophy, a retinal disease that affects the macula and results in a well-demarcated circumscribed area of atrophy of the pigment epithelium and choriocapillaris.
A form of central areolar choroidal dystrophy, a retinal disease that affects the macula and results in a well-demarcated circumscribed area of atrophy of the pigment epithelium and choriocapillaris. CACD1 inheritance is autosomal recessive.
An X-linked recessive disease characterized by a slowly progressive degeneration of the choroid, photoreceptors, and retinal pigment epithelium. Affected males develop night blindness in their teenage years followed by loss of peripheral vision and complete blindness at middle age. Carrier females are generally asymptomatic but funduscopic examination often shows patchy areas of chorioretinal atrophy.
Chronic atrial and intestinal dysrhythmia
A disease characterized by dysregulation of the cardiac sinus node resulting in sick sinus syndrome, in association with chronic intestinal pseudo-obstruction, a disorder of gastrointestinal motility in which intestinal obstruction occurs in the absence of a mechanical obstacle.
Chronic infantile neurologic cutaneous and articular syndrome
Cryopyrin-associated periodic syndrome 3
Neonatal onset multisystem inflammatory disease
Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation.
Sensorineural deafness with partial agenesis of the corpus callosum and arachnoid cysts
An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal.
Developmental delay, intellectual disability, obesity, and dysmorphic features
An autosomal dominant disorder characterized by developmental delay, intellectual disability, autistic features, anxiety, hypotonia, obesity, and dysmorphic features.
Hypobetalipoproteinemia with accumulation of apolipoprotein B-like protein in intestinal cells
An autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. The condition is characterized by deficiency of fat-soluble vitamins, low blood cholesterol levels, and a selective absence of chylomicrons from blood. Affected individuals accumulate chylomicron-like particles in membrane-bound compartments of enterocytes, which contain large cytosolic lipid droplets.
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Primary ciliary dyskinesia 10 with or without situs inversus
Primary ciliary dyskinesia 11 without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Primary ciliary dyskinesia 12 without situs inversus
Primary ciliary dyskinesia 13 with or without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. At ultrastructural level, CILD13 is characterized by a marked reduction or absence of both dynein arms from the patients cilia.
Primary ciliary dyskinesia 14 with or without situs inversus
Primary ciliary dyskinesia 15 with or without situs inversus
Primary ciliary dyskinesia 16 with or without situs inversus
Primary ciliary dyskinesia 17 with or without situs inversus
Primary ciliary dyskinesia 18 with or without situs inversus
Primary ciliary dyskinesia 19 with or without situs inversus
Primary ciliary dyskinesia 2 with or without situs inversus
Primary ciliary dyskinesia 20 with or without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. Unlike other forms of CILD characterized by reduced fertility, patients with CILD20 do not appear to be infertile.
Primary ciliary dyskinesia 21 without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Primary ciliary dyskinesia 22 with or without situs inversus
Primary ciliary dyskinesia 23 with or without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Situs inversus is not observed in CILD24 patients.
Primary ciliary dyskinesia 25 with or without situs inversus
Primary ciliary dyskinesia 26 with or without situs inversus
Primary ciliary dyskinesia 27 with or without situs inversus
Primary ciliary dyskinesia 28 with or without situs inversus
Primary ciliary dyskinesia without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD29 patients do not exhibit situs inversus, a congenital abnormality in which visceral organs are opposite to their normal positions (situs solitus) due to lateral transposition.
Ciliary dyskinesia, primary, 3, with or without situs inversus
Primary ciliary dyskinesia 30 with or without situs inversus
Ciliary dyskinesia, primary, 32, without situs inversus
A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia.
Ciliary dyskinesia, primary, 33, without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD33 inheritance is autosomal recessive.
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD34 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 35 with or without situs inversus
Primary ciliary dyskinesia 35 with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD35 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 36, X-linked
Ciliary dyskinesia, primary, 36, with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD36 inheritance is X-linked recessive. About half of CILD36 patients have laterality defects due to ciliary dysfunction at the embryonic node.
Ciliary dyskinesia, primary, 37, with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD37 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 38, with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD38 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 39, with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD39 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 40, with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD40 inheritance is autosomal recessive.
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD41 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 42, without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Other more variable features may include infertility and mild hydrocephalus. Patients with this form of the disorder do not have situs abnormalities. CILD42 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 43 with or without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients with this disorder also develop significant obstructive hydrocephalus. Other more variable features include infertility and about a 50% chance of situs inversus or other left-right asymmetry defects. CILD43 inheritance is autosomal dominant.
Ciliary dyskinesia, primary, 44 without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD44 inheritance is autosomal recessive.
Ciliary dyskinesia, primary, 45, without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD45 is an autosomal recessive form characterized by onset of symptoms in infancy or early childhood. Male patients have infertility due to immotile sperm.
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD46 is an autosomal recessive form. No situs abnormalities have been observed.
Ciliary dyskinesia, primary, 47, and lissencephaly
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD47 is an autosomal recessive form characterized by onset soon after birth or in early childhood. Affected individuals also have neurologic features, such as impaired intellectual development and central hypotonia, associated with structural brain abnormalities, most notably lissencephaly and thin or absent corpus callosum. No situs abnormalities have been observed.
Ciliary dyskinesia, primary, 48, without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD48 is an autosomal recessive form. No situs abnormalities have been observed.
Ciliary dyskinesia, primary, 49, without situs inversus
A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD49 is an autosomal recessive form without situs abnormalities. Affected males also show infertility due to defective flagellar morphology and function.
Primary ciliary dyskinesia 5 with or without situs inversus
An autosomal recessive form of primary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD5 is characterized by early onset of a progressive decline in lung function due to an inability to clear mucus and particles from the airways. Affected individuals have recurrent infections of the sinuses, ears, airways, and lungs. Sperm motility is also decreased. Individuals with CILD5 do not have situs inversus.
Primary ciliary dyskinesia 9 with or without situs inversus
Cerebellar hypoplasia, cataracts, impaired intellectual development, congenital microcephaly, dystonia, dyserythropoietic anemia, and growth retardation
An autosomal dominant syndrome characterized by global developmental delay, severely impaired intellectual development, poor or absent speech, microcephaly, growth retardation, poor motor skills with inability to walk, hypotonia and spasticity, and cataracts. Cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination are apparent on brain imaging. Affected individuals show hematologic abnormalities mostly consistent with congenital dyserythropoietic anemia.
A liver disease characterized by severe panlobular liver-cell swelling with Mallory body formation, prominent pericellular fibrosis, and marked deposits of copper. Clinical features include abdomen swelling, jaundice and pulmonary hypertension.
The classic form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. It is a disorder of the urea cycle, usually manifesting in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder form can develop later in childhood or adulthood.
A form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. Citrullinemia type 2 is characterized by neuropsychiatric symptoms including abnormal behaviors, loss of memory, seizures and coma. Death can result from brain edema. Onset is sudden and usually between the ages of 20 and 50 years.
An X-linked recessive disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus.
Capillary malformation of the lower lip, lymphatic malformation of face and neck, asymmetry of face and limbs, and partial/generalized overgrowth
A syndrome characterized by capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of face and limbs and partial or generalised overgrowth.
An autosomal dominant disease characterized by intellectual disability, delayed psychomotor development, behavioral abnormalities, variable dysmorphic facial features, tall stature, obesity, and macrocephaly.
A congenital fissure of the soft and/or hard palate, due to faulty fusion. Isolated cleft palate is not associated with cleft lips. Some patients may manifest other craniofacial dysmorphic features, intellectual disability, and osteoporosis.
Cleft palate with or without ankyloglossia, X-linked
X-linked cleft palate with ankyloglossia
A congenital mouth abnormality characterized by fissure of the soft and/or hard palate, due to faulty fusion. Some patients also manifest ankyloglossia, a condition in which movements of the tongue are restricted. Complete ankyloglossia is due to fusion between the tongue and the floor of the mouth. Partial ankyloglossia is due to a short lingual frenum or one which is attached too near the tip of the tongue.
Cleft palate, cardiac defects, and impaired intellectual development
Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies
An autosomal dominant disease characterized by multiple congenital malformations, mild-to-severe intellectual disability with poor speech, and delayed psychomotor development. Congenital malformations include heart defects, cleft lip/palate, distally-placed thumbs and toes, and cutaneous syndactyly between the second and third toes.
Cleft palate, proliferative retinopathy, and developmental delay
An autosomal recessive disorder characterized by mild to severe intellectual disability with delayed or absent speech, hypotonia, cleft palate, proliferative retinopathy, and combined sensorineural and conductive hearing loss. Brain imaging shows ventriculomegaly, widened subarachnoid spaces, partial agenesis of the corpus callosum, hypoplastic cerebellar vermis, and Dandy Walker malformation.
Cleft palate, psychomotor retardation, and distinctive facial features
A syndrome characterized by cleft palate, developmental delay, psychomotor retardation, and facial dysmorphic features including a prominent forehead, slightly arched eyebrows, elongated palpebral fissures, a wide nasal bridge, thin lips, and widely spaced teeth. Cleft palate is a congenital fissure of the soft and/or hard palate, due to faulty fusion.
A form of cleidocranial dysplasia, a rare skeletal disorder with significant clinical variability, even within families. Patients typically present with delayed closure of cranial sutures and fontanels with multiple Wormian bones, retarded ossification of the skull, shortening of the distal phalanges, dental anomalies including supernumerary teeth and eruption failure, clavicular hypoplasia or aplasia, wide pubic symphysis, vertebral anomalies, and short stature. CLCD1 inheritance is autosomal dominant.
A form of cleidocranial dysplasia, a rare skeletal disorder with significant clinical variability, even within families. Patients typically present with delayed closure of cranial sutures and fontanels with multiple Wormian bones, retarded ossification of the skull, shortening of the distal phalanges, dental anomalies including supernumerary teeth and eruption failure, clavicular hypoplasia or aplasia, wide pubic symphysis, vertebral anomalies, and short stature. Craniofacial features are subtle and characterized by prominent parietal and frontal bones, widely spaced eyes, depressed nasal bridge and small maxilla. Some CLCD2 patients present mild to moderate developmental delay. CLCD2 inheritance is autosomal dominant.
Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly
A congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities. Clubfoot may occur in isolation or as part of a syndrome. Some patients present tibial hemimelia, bilateral patellar hypoplasia, and preaxial mirror-image polydactyly.
Cerebellar vermis hypo/aplasia oligophrenia congenital ataxia ocular coloboma and hepatic fibrosis
Joubert syndrome with congenital hepatic fibrosis
A form of COACH syndrome, a disorder characterized by cerebellar vermis hypoplasia, developmental delay, impaired intellectual development, ataxia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable. COACH1 inheritance is autosomal recessive.
A form of COACH syndrome, a disorder characterized by cerebellar vermis hypoplasia, developmental delay, impaired intellectual development, ataxia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable. COACH2 inheritance is autosomal recessive.
A form of COACH syndrome, a disorder characterized by cerebellar vermis hypoplasia, developmental delay, impaired intellectual development, ataxia, and hepatic fibrosis. Patients present the molar tooth sign, a midbrain-hindbrain malformation pathognomonic for Joubert syndrome and related disorders. Other features, such as coloboma and renal cysts, may be variable. COACH3 inheritance is autosomal recessive.
A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in intellectual disability. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
A lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin.
Cerebral, ocular, dental, auricular, and skeletal anomalies syndrome
A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts.
An autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form.
An autosomal recessive multisystem disorder characterized by early-onset deafness, optic atrophy, mild intellectual disability, peripheral neuropathy, obesity, livedo reticularis, and cardiac valvulopathy.
A fatal encephalomyopathic form of coenzyme Q10 deficiency with nephrotic syndrome. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form.
Autosomal recessive cerebellar ataxia type 2
Spinocerebellar ataxia autosomal recessive 9
An autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Patient manifest gait ataxia and cerebellar atrophy with slow progression. Additional features include brisk tendon reflexes and Hoffmann sign, variable psychomotor retardation and variable seizures.
A form of coenzyme Q10 deficiency, an autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form.
Steroid-resistant nephrotic syndrome with sensorineural deafness
An autosomal recessive disorder characterized by onset in infancy of severe progressive nephrotic syndrome resulting in end-stage renal failure and sensorineural deafness. Renal biopsy usually shows focal segmental glomerulosclerosis.
An autosomal recessive disorder resulting from mitochondrial dysfunction and characterized by decreased levels of coenzyme Q10, and severe cardiac or neurologic symptoms soon after birth, usually resulting in death. Rarely, symptoms may have later onset.
An autosomal recessive disorder resulting from mitochondrial dysfunction and characterized by decreased levels of coenzyme Q10. Patients manifest neonatal lung hypoplasia, contractures, early infantile hypertension and cardiac hypertrophy, secondary to prenatal kidney dysplasia, with neonatal and infantile renal dysfunction. Clinical features also include progressive peripheral neuropathy, muscular hypotonia and atrophy, and mild psychomotor delay with hearing and visual impairment.
A form of coenzyme Q10 deficiency, an autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form. COQ10D9 patients show cerebellar ataxia with cerebellar atrophy. Additional features include generalized tonic-clonic seizures, and cognitive disability. Disease onset is in the first decade of life.
An X-linked disorder characterized by intellectual disability associated with facial and digital dysmorphisms, progressive skeletal malformations, growth retardation, hearing deficit and paroxysmal movement disorders.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. CSS11 is an autosomal dominant form characterized by developmental delay, intellectual disability, hypotonia, feeding difficulties, and small hands and feet.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. CSS12 is an autosomal dominant form characterized by global developmental delay with variably impaired intellectual development, speech and language delay, and behavioral abnormalities, such as autism or hyperactivity. Most CSS12 patients do not have the classic hypoplastic fifth digit/nail abnormalities that are often observed in other forms the disease.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. CSS6 inheritance is autosomal dominant.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. CSS7 inheritance is autosomal dominant.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. CSS8 patients manifest prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features such as hypertrichosis, thick eyebrows, thin upper lip vermilion, and upturned nose. CSS8 inheritance is autosomal dominant.
A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. CSS9 is an autosomal dominant form characterized by dysmorphic facial features, microcephaly, growth deficiency, hypoplastic fifth toenails, and mild intellectual disability.
Cognitive impairment with or without cerebellar ataxia
A disorder characterized by markedly delayed cognitive and motor development, attention deficit disorder, and cerebellar ataxia. Features include bilateral esophoria, strabismatic amblyopia, unsustained gaze evoked nystagmus on horizontal gaze, ataxic gait, dysmetria in the upper limbs and dysarthria, with normal strength, tone, and reflexes.
A rare autosomal recessive disorder characterized by obesity, hypotonia, intellectual deficit, characteristic craniofacial dysmorphism and abnormalities of the hands and feet. Characteristic facial features include high-arched or wave-shaped eyelids, a short philtrum, thick hair and low hairline.
An autosomal dominant overgrowth disorder characterized by accelerated osseous maturation, advanced bone age, skeletal abnormalities including flaring of the metaphyses of the long bones, large hands with long fingers and camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial features, and variable intellectual disability.
A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy.
Bone fragility with craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features
A form of Cole-Carpenter syndrome, a disorder characterized by features of osteogenesis imperfecta such as bone deformities and severe bone fragility with frequent fractures, in association with craniosynostosis, ocular proptosis, hydrocephalus, growth failure and distinctive facial features. Craniofacial findings include marked frontal bossing, midface hypoplasia, and micrognathia. Despite the craniosynostosis and hydrocephalus, intellectual development is normal. CLCRP1 inheritance is autosomal dominant.
A form of Cole-Carpenter syndrome, a disorder characterized by features of osteogenesis imperfecta such as bone deformities and severe bone fragility with frequent fractures, in association with craniosynostosis, ocular proptosis, hydrocephalus, growth failure and distinctive facial features. Craniofacial findings include marked frontal bossing, midface hypoplasia, and micrognathia. Despite the craniosynostosis and hydrocephalus, intellectual development is normal. CLCRP2 inheritance is autosomal recessive.
An ocular defect that is due to malclosure of the fetal intraocular fissure affecting the optic nerve head. In some affected individuals, it appears as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disk.
Coloboma, congenital heart disease, ichthyosiform dermatosis, impaired intellectual development, and ear anomalies syndrome
Glycosylphosphatidylinositol biosynthesis defect 5
An extremely rare autosomal recessive multisystem disorder clinically characterized by colobomas, congenital heart defects, migratory ichthyosiform dermatosis, intellectual disability, and ear anomalies including conductive hearing loss. Other clinical features include distinctive facial features, abnormal growth, genitourinary abnormalities, seizures, and feeding difficulties.
A set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia.
An ocular anomaly resulting from abnormal morphogenesis of the optic cup and stalk, and incomplete fusion of the fetal intra-ocular fissure during gestation. The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia.
Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or impaired intellectual development
An autosomal dominant disease characterized by uveal colobomata, microphthalmia, cataract and cleft lip/palate. Considerable variability is observed among patients, uveal colobomata being the most constant feature. Some patients manifest intellectual disability of varying degree and/or sensorineural, mid-frequency hearing loss.
Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness
An autosomal recessive syndrome characterized by severe microphthalmia, profound congenital sensorineural hearing loss, lack of pigment in the hair, skin, and eyes, macrocephaly, facial dysmorphism, and osteopetrosis.
A color vision defect characterized by a dichromasy in which red and green are confused, without loss of luminance or shift or shortening of the spectrum. Dichromasy is due to the use of only two types of photoreceptors, blue plus red in deuteranopia and blue plus green in protanopia.
A color vision defect characterized by a dichromasy in which red and green are confused, with loss of luminance and shift of brightness and hue curves toward the short wave end of the spectrum. Dichromasy is due to the use of only two types of photoreceptors, blue plus red in deuteranopia and blue plus green in protanopia.
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Susceptibility to colorectal adenoma and cancer
Susceptibility to colorectal cancer on chromosome 9
Susceptibility to colorectal cancer on chromosome 19q
Susceptibility to colorectal cancer on chromosome 12q24
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. CRCS12 is characterized by a high-penetrance predisposition to the development of colorectal adenomas and carcinomas, with a variable tendency to develop multiple and large tumors. Onset is usually before age 40 years. The histologic features of the tumors are unremarkable.
Susceptibility to colorectal cancer on chromosome 18
Susceptibility to colorectal cancer on chromosome 15
Combined cellular and humoral immune defects with granulomas
Immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography.
Combined D-2- and L-2-hydroxyglutaric aciduria
An autosomal recessive neurometabolic disorder characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Brain imaging shows abnormalities including enlarged ventricles, delayed myelination, and germinal layer cysts.
Combined deficiency of vitamin K-dependent clotting factors 1
Multiple coagulation factor deficiency III
VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K.
Combined deficiency of vitamin K-dependent clotting factors 2
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
An autosomal recessive disorder due to an inborn error of folate metabolism. Variable clinical manifestations include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild intellectual disability, and lymphopenia.
Characterized by repeated episodes of pancreatitis, tuberous xanthomas and lipodystrophy and is caused by deficiency of both lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL).
Combined malonic and methylmalonic aciduria
A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline.
Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1
An autosomal dominant connective tissue disorder characterized by osteopenia, bone fragility, long bone fractures, blue sclerae, joint hyperextensibility, soft and hyperextensible skin, abnormal wound healing, easy bruising, and vascular fragility.
Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2
Combined oxidative phosphorylation deficiency 1
Hepatoencephalopathy early fatal progressive
A mitochondrial disease resulting in early rapidly progressive hepatoencephalopathy.
Combined oxidative phosphorylation deficiency 10
Cardiomyopathy infantile hypertrophic mitochondrial and lactic acidosis
An autosomal recessive disorder resulting in variable defects of mitochondrial oxidative respiration. Affected individuals present in infancy with hypertrophic cardiomyopathy and lactic acidosis. The severity is variable, but can be fatal in the most severe cases.
Combined oxidative phosphorylation deficiency 11
Infantile encephaloneuromyopathy due to mitochondrial translation defect
A severe, multisystemic, autosomal recessive, disorder characterized by deficiencies of multiple mitochondrial respiratory enzymes leading to neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures.
Combined oxidative phosphorylation deficiency 12
Leukoencephalopathy with thalamus and brainstem involvement and high lactate
An autosomal recessive, mitochondrial, neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability.
Combined oxidative phosphorylation deficiency 13
A mitochondrial disorder characterized by early onset severe encephalomyopathy, dystonia, choreoathetosis, bucofacial dyskinesias and combined mitochondrial respiratory chain deficiency. Nerve conductions velocities are decreased. Levels of plasma and cerebrospinal fluid lactate are increased.
Combined oxidative phosphorylation deficiency 14
A severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes.
Combined oxidative phosphorylation deficiency 15
An autosomal recessive, mitochondrial, neurologic disorder characterized by features of Leigh syndrome and combined oxidative phosphorylation deficiency. Clinical features include mild global developmental delay, white matter abnormalities, ataxia, incoordination, speech and reading difficulties, T2-weighted hyperintensities in the basal ganglia, corpus callosum, and brainstem.
Combined oxidative phosphorylation deficiency 16
An autosomal recessive, mitochondrial disorder characterized by hypertrophic cardiomyopathy, liver steatosis, and decreased levels of mitochondrial complexes I and IV in heart and skeletal muscle.
Combined oxidative phosphorylation deficiency 17
An autosomal recessive disorder of mitochondrial dysfunction characterized by onset of severe hypertrophic cardiomyopathy in the first year of life. Other features include hypotonia, poor growth, lactic acidosis, and failure to thrive. The disorder may be fatal in early childhood.
Combined oxidative phosphorylation deficiency 18
An autosomal recessive disorder of mitochondrial dysfunction characterized by intrauterine growth retardation, hypotonia, visual impairment, speech delay, and lactic acidosis associated with decreased mitochondrial respiratory chain activity. Affected patients may also show hematologic abnormalities, mainly macrocytic anemia.
Combined oxidative phosphorylation deficiency 19
A mitochondrial disorder characterized by respiratory distress, hypotonia, and severe lactic acidosis in the newborn period. Other features include gastroesophageal reflux and elevated liver enzymes with normal synthetic function.
Combined oxidative phosphorylation deficiency 2
Agenesis of corpus callosum with dysmorphism and fatal lactic acidosis
A mitochondrial disease resulting in fatal neonatal metabolic acidosis with agenesis of the corpus callosum.
Combined oxidative phosphorylation deficiency 20
A disorder due to mitochondrial respiratory chain complex defects. Clinical features are variable and include muscle weakness with hypotonia, central neurological disease with progressive external ophthalmoplegia, ptosis and ataxia, delayed psychomotor development, cardiomyopathy, abnormal liver function, facial dysmorphism, microcephaly and epilepsy.
Combined oxidative phosphorylation deficiency 21
A mitochondrial disorder characterized by a lethal encephalomyopathy. Shortly after birth, affected individuals manifest axial hypotonia, limb hypertonia, psychomotor delay, and increased serum lactate. Additional features include subsarcolemmal lipofuscin-positive deposits in muscle, cerebral spongiosis, and hepatic steatosis.
Combined oxidative phosphorylation deficiency 22
A mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure.
Combined oxidative phosphorylation deficiency 23
An autosomal recessive mitochondrial disorder characterized by hypertrophic cardiomyopathy and/or neurologic symptoms with onset in early childhood. Disease features include hypertrophic cardiomyopathy, hypotonia, delayed psychomotor development, lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Disease severity is variable, ranging from death in early infancy to survival into the second decade of life.
Combined oxidative phosphorylation deficiency 24
An autosomal recessive mitochondrial disorder with wide phenotypic variability. Some patients have a milder form affecting only skeletal muscle, whereas others may have a more severe disorder, reminiscent of Alpers syndrome. Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter.
Combined oxidative phosphorylation deficiency 25
A mitochondrial disorder resulting in developmental delay, growth failure, and sensorineural hearing loss.
Combined oxidative phosphorylation deficiency 27
An autosomal recessive mitochondrial disorder characterized by multiple mitochondrial respiratory-chain-complex deficiencies causing neurological regression, progressive cognitive decline, complex movement disorder, epileptic encephalopathy, progressive spastic tetraparesis, and progressive impairment of vision and hearing.
Combined oxidative phosphorylation deficiency 28
An autosomal recessive mitochondrial disorder characterized by decreased activities of respiratory chain enzymes, and variable clinical manifestations. Clinical features include episodic metabolic decompensation beginning in infancy, mild muscle weakness, cardiorespiratory insufficiency, developmental delay, or even death.
Combined oxidative phosphorylation deficiency 29
An autosomal recessive, infantile-onset, neurodegenerative disorder characterized by decreased activities of mitochondrial respiratory complexes I and III, severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy.
Combined oxidative phosphorylation deficiency 3
Concentric cardiomyopathy hypotonia and lactic acidosis
Encephalomyopathy respiratory failure and lactic acidosis
A mitochondrial disease resulting in severe metabolic acidosis with encephalomyopathy or with hypertrophic cardiomyopathy. Patients show a severe defect in mitochondrial translation leading to a failure to assemble adequate amounts of three of the oxidative phosphorylation complexes.
Combined oxidative phosphorylation deficiency 30
An autosomal recessive, severe mitochondrial disease characterized by lactic acidosis, hypotonia, feeding difficulties, deafness, and respiratory failure with fatal issue. Patient skeletal muscle cells show decreased activities of mitochondrial complexes I, III and IV.
Combined oxidative phosphorylation deficiency 31
An autosomal recessive, severe mitochondrial disease with multisystemic manifestations appearing soon after birth or in early infancy. Clinical features include left ventricular non-compaction, global developmental delay, severe hypotonia, seizures, cataract, and abnormal movements. Death may occur in early childhood.
Combined oxidative phosphorylation deficiency 32
An autosomal recessive disorder due to deficiency of mitochondrial respiratory chain complexes, I, III and IV, and characterized by delayed psychomotor development and neurodevelopmental regression. Additional variable symptoms include poor or absent speech, inability to walk, and abnormal movements.
Combined oxidative phosphorylation deficiency 33
An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia.
Combined oxidative phosphorylation deficiency 34
An autosomal recessive disorder caused by mitochondrial dysfunction and combined respiratory chain deficiencies of complexes I, III and IV. Clinical manifestations are variable and include congenital sensorineural deafness, lactic acidemia, and progressive hepatic and renal failure.
Combined oxidative phosphorylation deficiency 35
An autosomal recessive disorder caused by defective mitochondrial metabolism and deficiencies of mitochondrial respiratory enzyme complexes. Clinical manifestations include global developmental delay, intellectual disability, microcephaly, and early-onset seizures.
Combined oxidative phosphorylation deficiency 36
An autosomal recessive, multisystem disease resulting from deficiencies of mitochondrial respiratory enzyme complexes and mitochondrial dysfunction. Clinical manifestations include sensorineural hearing impairment, mild developmental delay, hypoglycemia, and intellectual disability.
Combined oxidative phosphorylation deficiency 37
An autosomal recessive disorder due to mitochondrial dysfunction and characterized by hypotonia, failure to thrive, progressive neurodegeneration with neurologic deterioration after the first months of life, global developmental delay, as well as liver dysfunction. Some patients may have hypertrophic cardiomyopathy, loss of vision and hearing, and/or seizures. Death in first months or years of life is observed in most patients.
Combined oxidative phosphorylation deficiency 38
An autosomal recessive disorder due to mitochondrial dysfunction and characterized by perinatal hypertrophic cardiomyopathy, growth retardation, muscle hypotonia, elevated lactate, dysmorphy and intellectual disability.
Combined oxidative phosphorylation deficiency 39
An autosomal recessive disorder due to mitochondrial dysfunction and characterized by global developmental delay, axial hypotonia, dystonia, dysarthria, impaired intellectual development with poor speech, and deficiencies of the mitochondrial respiratory chain enzyme complexes. Neuroimaging shows abnormalities in the putamen and caudate nuclei, along with subcortical white matter involvement.
Combined oxidative phosphorylation deficiency 4
A mitochondrial disease resulting in neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA-related mitochondrial respiratory chain complexes.
Combined oxidative phosphorylation deficiency 40
An autosomal recessive mitochondrial disorder characterized by prenatal or infantile onset, fetal hydrops, severe hypertrophic cardiomyopathy, poor growth, sensorineural hearing loss, hepatic dysfunction, lactic acidosis, and decreased activities of mitochondrial respiratory complexes I, III, IV, and V. The disorder is lethal, with death occurring in infancy.
Combined oxidative phosphorylation deficiency 41
An autosomal recessive mitochondrial disorder characterized by prenatal onset, fetal hydrops, intrauterine growth retardation, hypertrophic cardiomyopathy, respiratory insufficiency, lactic acidosis, and decreased activities of mitochondrial respiratory complexes I, III, IV, and V. The disorder is lethal, with death occurring in the perinatal period.
Combined oxidative phosphorylation deficiency 42
An autosomal recessive mitochondrial disorder characterized by onset in the first months of life, cardiomyopathy, respiratory insufficiency, lactic acidosis, anemia, and variable impairment of mitochondrial respiratory complexes I, III, and IV. Death occurs in infancy.
Combined oxidative phosphorylation deficiency 43
An autosomal recessive mitochondrial disorder characterized by onset at birth, intrauterine growth retardation, hypotonia, myopathy, feeding difficulties associated with gastroesophageal reflux, and persistently elevated serum lactate and creatine kinase. Brain imaging shows delayed myelination. Muscle biopsy shows decreased activities of mitochondrial respiratory chain complexes I, III, and IV.
Combined oxidative phosphorylation deficiency 44
An autosomal recessive mitochondrial disorder characterized by onset in infancy or early childhood of global developmental delay, hypotonia, and abnormal movements. Combined oxidative phosphorylation deficiency is present in skeletal muscle. Most patients have seizures associated with status epilepticus. Additional variable features include optic atrophy, hypertrophic cardiomyopathy, stroke-like episodes, and increased lactate levels in serum and cerebrospinal fluid.
Combined oxidative phosphorylation deficiency 45
An autosomal recessive mitochondrial disorder with onset in utero and characterized by poor overall growth, failure to thrive, global developmental delay, poor or absent speech, seizures, hypotonia, loss of walking, acute progressive neurologic deterioration, brain lesions, and facial dysmorphism. Laboratory studies show increased serum lactate and decreased mitochondrial respiratory chain enzyme activity in patient tissues.
Combined oxidative phosphorylation deficiency 46
An autosomal recessive disorder characterized by childhood-onset mitochondrial respiratory chain complex deficiencies, particularly complexes I and IV, and hepatic disease.
Combined oxidative phosphorylation deficiency 47
An autosomal recessive, multisystemic, mitochondrial disorder characterized by intrauterine growth retardation, swallowing difficulties with failure to thrive, hypoglycemia, dehydration, and hepatomegaly. Additional features include global developmental delay with impaired intellectual development and absent speech, microcephaly, facial dysmorphism, cataract, sensorineural deafness, skeletal features, and cryptorchidism. Laboratory studies show metabolic acidosis, increased serum lactate, and variably impaired activity of mitochondrial respiratory complexes I, III, IV, and V in different tissues.
Combined oxidative phosphorylation deficiency 48
An autosomal recessive, mitochondrial encephalomyopathy characterized by global developmental delay, microcephaly, failure to thrive, hypotonia, muscle weakness, external ophthalmoplegia, and seizures. Laboratory studies show metabolic acidosis, increased serum lactate, and combined oxidative phosphorylation deficiency in skeletal muscle.
Combined oxidative phosphorylation deficiency 49
An autosomal recessive, mitochondrial myopathy characterized by progressive muscle weakness, intermittent muscle pain, exercise intolerance, elevated serum creatine kinase, and deficiencies of multiple respiratory chain enzymes.
Combined oxidative phosphorylation deficiency 5
A mitochondrial disease resulting in severe metabolic acidosis, edema, hypertrophic cardiomyopathy, tubulopathy, and hypotonia.
Combined oxidative phosphorylation deficiency 50
An autosomal recessive, mitochondrial encephalomyopathy characterized by intrauterine growth retardation, poor overall growth, delayed psychomotor development, hypotonia, muscle weakness, progressive loss of ambulation, and mitochondrial oxidative phosphorylation deficiency in patient tissues. Brain imaging shows partial agenesis of the corpus callosum.
Combined oxidative phosphorylation deficiency 51
An autosomal recessive, mitochondrial disorder characterized by intrauterine growth retardation, low birth weight, poor overall growth, progressive limb rigidity, delayed psychomotor development, hearing loss, and optic atrophy. Brain imaging shows abnormal bilateral signs at the basal ganglia and brainstem. Patient cells show decreased mitochondrial complex I and IV levels and activities, and generalized mitochondrial translation defects.
Combined oxidative phosphorylation deficiency 52
An autosomal recessive mitochondrial disorder with onset in infancy, characterized by lactic acidemia, hypotonia, respiratory chain complex II and III deficiency, multisystem organ failure and abnormal mitochondria.
Combined oxidative phosphorylation deficiency 53
Global developmental delay, progressive microcephaly, structural brain abnormalities, and autoinflammation
An autosomal recessive mitochondrial disorder characterized by global developmental delay, hypomyelination, cerebral atrophy, microcephaly, liver dysfunction, and recurrent autoinflammation.
Combined oxidative phosphorylation deficiency 54
An autosomal recessive, multisystem disorder with highly variable manifestations resulting from defective mitochondrial transcription and translation. Clinical features include early-onset sensorineural hearing loss, sometimes associated with global developmental delay or primary ovarian failure, peripheral hypertonia, seizures, muscle weakness, behavioral abnormalities, and leukoencephalopathy on brain imaging. Serum lactate may or may not be elevated.
Combined oxidative phosphorylation deficiency 55
A mitochondrial disease characterized by global developmental delay, hypotonia, short stature, and impaired intellectual development with speech disabilities in childhood. Indolent progressive external ophthalmoplegia may be present in some patients. COXPD55 transmission pattern is consistent with autosomal dominant inheritance in some families, and with autosomal recessive inheritance in others.
Combined oxidative phosphorylation deficiency 56
An autosomal recessive mitochondrial disease characterized by lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis.
Combined oxidative phosphorylation deficiency 57
An autosomal recessive mitochondrial disease characterized by multisystemic features including encephalopathy, neurodevelopmental regression, ocular anomalies, decreased vision, auditory neuropathy, sensorineural hearing loss, and cardiac defects. Disease severity is variable, ranging from premature death in infancy to permanent disability in young adulthood.
Combined oxidative phosphorylation deficiency 6
Encephalomyopathy mitochondrial X-linked
A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy.
Combined oxidative phosphorylation deficiency 7
A mitochondrial disease resulting in encephalomyopathy. Clinical manifestations include psychomotor delay and regression, ataxia, optic atrophy, nystagmus and muscle atrophy and weakness.
Combined oxidative phosphorylation deficiency 8
Cardiomyopathy hypertrophic mitochondrial fatal infantile
A mitochondrial disease characterized by a lethal infantile hypertrophic cardiomyopathy, generalized muscle dysfunction and some neurologic involvement. The liver is not affected.
Combined oxidative phosphorylation deficiency 9
A mitochondrial disease characterized by failure to thrive, poor feeding, hypertrophic cardiomyopathy, hepatomegaly, and psychomotor retardation. Death in infancy has been observed in some cases.
An autosomal recessive storage disorder characterized by hepatosplenomegaly and severe neurologic disease, due to absence of all saposins. PSAPD has a fatal outcome in infancy.
A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. Skin and joint manifestations are common and renal disease is relatively rare. Patients with complement component 2 deficiency are also reported to have recurrent invasive infections.
Complement component 3 deficiency autosomal recessive
A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.
A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.
A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.
Complement component 6 deficiency subtotal
Complement component 8 deficiency type I
Complement component 8 deficiency type II
A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Some patients may develop dermatomyositis.
A disorder caused by impaired activation of the complement classical pathway. It generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.
A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.
An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway.
A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.
Autosomal recessive condition associated with a propensity to pyogenic infections.
Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy
An autosomal recessive disease characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease. Patients' T lymphocytes show increased complement activation causing surface deposition of complement and the generation of soluble C5a.
An autosomal dominant cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs.
An early-onset cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs.
An X-linked cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs.
Cone dystrophy with night blindness and supernormal rod responses KCNV2-related
Cone dystrophy with supernormal rod electroretinogram
A rare form of cone dystrophy associated with supernormal rod responses. The disorder is characterized by reduced visual acuity, photoaversion, night blindness, and abnormal color vision. At an early age, the retina shows subtle depigmentation at the macula and, later, more obvious areas of atrophy.
Cone dystrophy with night blindness and supernormal rod responses
An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
An autosomal dominant form of cone-rod dystrophy, a retinal disease characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
Retinal dystrophy with early macular involvement
A form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
An autosomal recessive form of cone-rod dystrophy, an inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
An autosomal recessive disease defined by the association of progressive cone-rod dystrophy with sensorineural hearing loss. Cone-rod dystrophy is characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa. In cone-rod dystrophy X-linked type 1 the degree of rod-photoreceptor involvement can be variable, with degeneration increasing as the disease progresses. Affected individuals (essentially all of whom are males) present with decreased visual acuity, myopia, photophobia, abnormal color vision, full peripheral visual fields, decreased photopic electroretinographic responses, and granularity of the macular retinal pigment epithelium. Although penetrance appears to be nearly 100%, there is variable expressivity with respect to age at onset and severity of symptoms.
Cone-rod synaptic disorder syndrome, congenital non-progressive
An autosomal recessive disorder characterized by reduced visual acuity, photophobia, nystagmus, distinctive electroretinographic features, neurodevelopmental delay, poor or absent language, autistic behaviors, and abnormal glucose homeostasis.
Cone-rod synaptic disorder, congenital non-progressive
Incomplete congenital stationary night blindness autosomal recessive
Night blindness, congenital stationary, 2B
A non-progressive retinal disorder characterized by stable low vision, nystagmus, photophobia, a normal or near-normal fundus appearance, and no night blindness.
Rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen.
Congenital amegakaryocytic thrombocytopenia
Disease characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies.
Congenital anomalies of kidney and urinary tract 2
A disorder encompassing a broad spectrum of renal and urinary tract malformations that include renal agenesis, kidney hypodysplasia, multicystic kidney dysplasia, duplex collecting system, posterior urethral valves and ureter abnormalities. Congenital anomalies of kidney and urinary tract are the commonest cause of chronic kidney disease in children.
Congenital anomalies of kidney and urinary tract 3
A disorder encompassing a broad spectrum of renal and urinary tract malformations that include renal agenesis, kidney hypodysplasia, multicystic kidney dysplasia, duplex collecting system, posterior urethral valves and ureter abnormalities. Congenital anomalies of kidney and urinary tract are the commonest cause of chronic kidney disease in children. CAKUT3 inheritance is autosomal dominant.
Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
An autosomal dominant disorder characterized by variable congenital anomalies of the kidney and urinary tract, sometimes resulting in renal dysfunction or failure, dysmorphic facial features, and abnormalities of the outer ear. Most patients have hearing loss, and some may have global developmental delay.
Congenital anomalies of the kidney and urinary tract 1
Congenital arthrogryposis with anterior horn cell disease
Lethal arthrogryposis with anterior horn cell disease
An autosomal recessive disorder characterized by fetal akinesia, arthrogryposis and motor neuron loss. The fetus often survives delivery, but dies early as a result of respiratory failure. Neuropathological findings resemble those of lethal congenital contracture syndrome type 1, but are less severe.
Congenital bilateral absence of the vas deferens
An autosomal recessive disease characterized by vas deferens aplasia resulting in azoospermia and male infertility. CBAVD may occur in isolation or as a manifestation of cystic fibrosis.
Congenital bilateral aplasia of the vas deferens, X-linked
A disease characterized by bilateral absence of vas deferens, obstructive azoospermia, and infertility.
3-beta-hydroxy-delta-5-C27-steroid oxidoreductase deficiency
Neonatal progressive intrahepatic cholestasis
Progressive familial intrahepatic cholestasis type 4
A primary defect in bile synthesis leading to progressive liver disease. Clinical features include neonatal jaundice, severe intrahepatic cholestasis, cirrhosis.
Cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency
A condition characterized by jaundice, intrahepatic cholestasis and hepatic failure. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.
A disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity is undetectable.
Intrahepatic cholestasis with defective conversion of trihydroxycoprostanic acid to cholic acid
A disorder characterized by the presence of trihydroxycoprostanic acid in the bile and absence of cholic acid. Patients manifest neonatal jaundice, intrahepatic cholestasis and bile duct deficiency.
An autosomal recessive disorder characterized by hepatosplenomegaly, hepatic fibrosis, progressive liver failure, and accumulation of peroxisomal C27-bile acid intermediates in plasma.
An inborn error of bile acid synthesis characterized by abnormally increased liver enzymes, hypolipidemia and low cholesterol, vitamin D deficiency, elevated plasma and urinary levels of C27 intermediate bile acids 3alpha,7alpha-dihydroxy-5beta-cholestanoic acid (DHCA) and 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid (THCA). Serum levels of phytanic and pristanic acids are normal. Clinical features include liver fibrosis, mild ataxia, delayed development, and cognitive impairment. Liver histology shows many thin fibrous septa, swollen hepatocytes, glycogenated nuclei, and focal acinar transformation, consistent with hepatocellular injury and regeneration, without signs of obvious cholestasis, cholate stasis, or steatosis. CBAS6 transmission pattern is consistent with autosomal recessive inheritance.
Congenital cataracts, facial dysmorphism, and neuropathy
An autosomal recessive developmental disorder characterized by a complex clinical phenotype with seemingly unrelated features involving multiple organs and systems. Developmental abnormalities include congenital cataracts and microcorneae, hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, facial dysmorphism and hypogonadism. Central nervous system involvement, with cerebral and spinal cord atrophy, may be the result of disrupted development with superimposed degenerative changes. Affected individuals are prone to severe rhabdomyolysis after viral infections and to serious complications related to general anesthesia (such as pulmonary edema and epileptic seizures).
Congenital cataracts, hearing loss, and neurodegeneration
An autosomal recessive disorder characterized by congenital cataracts, severe psychomotor retardation, and hearing loss associated with decreased serum ceruloplasmin and copper. Brain MRI shows cerebral and cerebellar atrophy and hypomyelination.
Congenital contractures of the limbs and face, hypotonia, and developmental delay
A disease characterized by congenital contractures of the limbs and face, resulting in characteristic facial features, abnormal tone, most commonly manifested as hypotonia, and variable degrees of developmental delay.
Congenital disorder of deglycosylation 1
Congenital disorder of glycosylation type Iv
An autosomal recessive multisystem disorder characterized by developmental delay, hypotonia, abnormal involuntary movements and alacrima or poor tear production. Other features include microcephaly, intractable seizures, abnormal eye movements and evidence of liver dysfunction, probably due to cytoplasmic accumulation of storage material in vacuoles.
Congenital disorder of deglycosylation 2
An autosomal recessive disorder characterized by facial dysmorphism, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis.
Carbohydrate-deficient glycoprotein syndrome type Ia
Congenital disorder of glycosylation type Ia
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1A is an autosomal recessive disorder characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism.
Congenital disorder of glycosylation 1AA
Congenital disorder of glycosylation, type 1aa
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1AA inheritance is autosomal recessive.
Carbohydrate-deficient glycoprotein syndrome type Ib
Congenital disorder of glycosylation type Ib
Protein-losing enteropathy-hepatic fibrosis syndrome
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1B is clinically characterized by protein-losing enteropathy.
Congenital disorder of glycosylation 1BB
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1BB inheritance is autosomal recessive.
Carbohydrate-deficient glycoprotein syndrome type V
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Congenital disorder of glycosylation 1CC
Congenital disorder of glycosylation, type Icc
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1CC is an X-linked recessive form mainly characterized by intellectual and developmental disability.
Carbohydrate-deficient glycoprotein syndrome type IV
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Some CDG1E patients have features consistent with a dystroglycanopathy and congenital muscular dystrophy, including O-mannosylation defect, camptodactyly, elevated creatine kinase, motor delay and dystrophic changes on muscel biopsy.
Congenital disorder of glycosylation type If
Congenital disorder of glycosylation type Ig
Congenital disorder of glycosylation type Ih
Congenital disorder of glycosylation type Ii
Congenital disorder of glycosylation type Ij
Congenital disorder of glycosylation type Ik
Congenital disorder of glycosylation type Il
Congenital disorder of glycosylation type Im
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1M is a very severe disease with death occurring in early life.
Congenital disorder of glycosylation type In
Congenital disorder of glycosylation type Ip
Congenital disorder of glycosylation type Iq
Ocular coloboma ichthyosis brain malformations and endocrine abnormalities
Congenital disorder of glycosylation type Ir
Congenital disorder of glycosylation type It
Congenital disorder of glycosylation type Iu
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Some CDG1U patients have dystrophic changes seen on muscle biopsy and reduced O-mannosyl glycans on alpha-dystroglycan.
Congenital disorder of glycosylation 1W, autosomal dominant
Congenital disorder of glycosylation, type Iw, autosomal dominant
A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1WAD patients show variable skeletal anomalies, short stature, macrocephaly, and dysmorphic features. Some have impaired intellectual development. Additional features include increased muscle tone and muscle cramps.
Congenital disorder of glycosylation 1W, autosomal recessive
Congenital disorder of glycosylation type Ix
Congenital disorder of glycosylation type Iy
Carbohydrate-deficient glycoprotein syndrome type II
Congenital disorder of glycosylation type IIa
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Congenital disorder of glycosylation type IIc
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The clinical features of CDG2C include intellectual disability, short stature, facial stigmata, and recurrent bacterial peripheral infections with persistently elevated peripheral leukocytes. Biochemically, CDG2C is characterized by a lack of fucosylated glycoconjugates, including selectin ligands.
Congenital disorder of glycosylation type IId
Congenital disorder of glycosylation type IIe
Congenital disorder of glycosylation type IIf
CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Congenital disorder of glycosylation type IIg
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Clinical features of CDG2G include failure to thrive, generalized hypotonia, growth retardation and mild psychomotor retardation. CDG2G is biochemically characterized by a defect in O-glycosylation as well as N-glycosylation.
Congenital disorder of glycosylation type IIh
Congenital disorder of glycosylation type IIi
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Congenital disorder of glycosylation type 2I is characterized by mild neurological impairments.
Congenital disorder of glycosylation type IIj
Congenital disorder of glycosylation type IIk
An autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Congenital disorders of glycosylation are caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins and a wide variety of clinical features. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Congenital disorder of glycosylation type IIl
A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Clinical features of CDG2L include neonatal intractable focal seizures, vomiting, loss of consciousness, intracranial bleeding due to vitamin K deficiency, and death in infancy.
Congenital disorder of glycosylation type IIm
Congenital disorder of glycosylation X-linked
Developmental and epileptic encephalopathy 22
Epileptic encephalopathy, early infantile, 22
An X-linked dominant, severe neurologic disorder characterized by developmental delay, hypotonia, ocular anomalies, and brain malformations. Othere more variable clinical features included seizures, hypsarrhythmia, poor feeding, microcephaly, recurrent infections, dysmorphic features, shortened limbs, and coagulation defects. Congenital disorders of glycosylation are caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins and a wide variety of clinical features. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Congenital disorder of glycosylation, type IIn
A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Congenital disorder of glycosylation, type IIo
A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2O is characterized by hepatosplenomegaly, liver failure, hypotonia, and psychomotor disability.
Congenital disorder of glycosylation, type IIp
A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2P is characterized by mild metabolic dysfunction, primarily affecting the liver. Psychomotor development is normal.
Congenital disorder of glycosylation, type IIq
A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. The transmission pattern of CDG2Q is consistent with autosomal recessive inheritance.
Congenital disorder of glycosylation, type IIr
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2R is an X-linked recessive disorder characterized by infantile onset of liver failure, recurrent infections due to hypogammaglobulinemia, and cutis laxa. Some patients may also have mild intellectual impairment and dysmorphic features.
Congenital disorder of glycosylation, type IIt
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2T is an autosomal recessive form characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioral abnormalities, epilepsy, chronic insomnia, white matter changes on brain imaging, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels.
Congenital disorder of glycosylation, type 2V
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2V is an autosomal recessive form characterized by neurodevelopmental delay and variable facial dysmorphic features.
Congenital disorder of glycosylation, type IIw
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2W is an autosomal dominant disorder characterized by liver dysfunction and coagulation deficiencies.
Congenital disorder of glycosylation, type IIy
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2Y is an autosomal recessive form characterized by poor overall growth and global developmental delay with impaired intellectual development. Other features may include hypotonia, seizures, brain imaging abnormalities, dysmorphic features, and various skeletal defects.
Congenital disorder of glycosylation, type IIz
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2Z is an autosomal recessive form characterized by a predominantly neurological phenotype with psychomotor disability, hypotonia, epilepsy and structural brain abnormalities. Biochemically, CDG2Z is characterized by combined O- and N-linked glycosylation defects.
Congenital disorder of glycosylation with defective fucosylation 1
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDGF1 is an autosomal recessive disorder, apparent from birth, characterized by poor growth, failure to thrive, hypotonia, skeletal anomalies, and delayed psychomotor development with intellectual disability.
Congenital disorder of glycosylation with defective fucosylation 2
A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. CDGF2 is an autosomal recessive disorder, apparent from birth, characterized by hypotonia, poor feeding, severely impaired intellectual and psychomotor development, seizures with epileptic encephalopathy, visual impairment and other ocular features, respiratory difficulty with frequent infections, as well as contractures. Brain imaging shows cerebellar and brainstem atrophy, hypoplasia or agenesis of the corpus callosum, and white matter abnormalities including periventricular leukomalacia.
Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. The manifestations of CEP are heterogeneous, ranging from nonimmune hydrops fetalis due to severe hemolytic anemia in utero to milder, later onset forms, which have only skin lesions due to cutaneous photosensitivity in adult life. The deficiency in UROS activity results in the non-enzymatic conversion of hydroxymethylbilane (HMB) into the uroporphyrinogen-I isomer.
Berardinelli-Seip congenital lipodystrophy type 1
Total lipodystrophy and acromegaloid gigantism
An autosomal recessive disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes.
Berardinelli-Seip congenital lipodystrophy type 2
Berardinelli-Seip congenital lipodystrophy type 3
Berardinelli-Seip congenital lipodystrophy type 4
Berardinelli-Seip congenital lipodystrophy type 4 with muscular dystrophy
A disorder characterized by the association of congenital generalized lipodystrophy with muscular dystrophy and cardiac anomalies. Congenital generalized lipodystrophy is characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes.
Congenital glucose/galactose malabsorption
Intestinal monosaccharide transporter deficiency. It is an autosomal recessive disorder manifesting itself within the first weeks of life. It is characterized by severe diarrhea and dehydration which are usually fatal unless glucose and galactose are eliminated from the diet.
Congenital heart defects and ectodermal dysplasia
An autosomal dominant syndrome characterized by atrial and/or ventricular septal congenital heart defects and variable features of ectodermal dysplasia, including sparse hair, dry skin, thin skin, fragile nails, premature loss of primary teeth, and small widely spaced teeth. Patients manifest developmental disabilities ranging from motor delay and delayed speech to global developmental retardation.
Congenital heart defects and skeletal malformations syndrome
An autosomal dominant disorder characterized by congenital heart disease with atrial and ventricular septal defects, variable skeletal abnormalities, and failure to thrive. Skeletal defects include pectus excavatum, scoliosis, and finger contractures. Some patient exhibit joint laxity.
Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder
An autosomal dominant syndrome characterized by atrial and/or ventricular septal congenital heart defects, facial dysmorphism with hypertelorism, upslanted palpebral fissures, epicanthal folds, ptosis, strabismus, posteriorly rotated ears, thin upper lip, and small mouth. Patients manifest global developmental delay, delayed walking and speech acquisition, and intellectual disability. Some patients have mild microcephaly, a small cerebral cortex, and agenesis of corpus callosum. More variable features include clinodactyly and/or camptodactyly of the fingers, hypotonia, and joint hypermobility.
Congenital heart defects, hamartomas of tongue, and polysyndactyly
A disease characterized by a constellation of anomalies including tongue hamartomas, polysyndactyly, and congenital heart defects such as atrioventricular canal and coarctation of the aorta.
Congenital heart defects, multiple types, 1, X-linked
X-linked congenital heart defects nonsyndromic 1
X-linked congenital heart disease nonsyndromic 1
A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions.
Congenital heart defects, multiple types, 2
Congenital heart defects non-syndromic 2
A disease characterized by congenital developmental abnormalities involving structures of the heart. CHTD2 patients have left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation.
Congenital heart defects, multiple types, 4
A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions.
Congenital heart defects, multiple types, 5
A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, patent ductus arteriosus, and tetralogy of Fallot. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. CHTD5 inheritance can be autosomal dominant or recessive.
Congenital heart defects, multiple types, 6
Transposition of the great arteries, dextro-looped 3
An autosomal dominant disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, transposition of the great arteries, double-outlet right ventricle, total anomalous pulmonary venous return, pulmonary stenosis or atresia, atrioventricular canal, ventricular septal defect, and hypoplastic left or right ventricle.
Congenital heart defects, multiple types, 7
An autosomal dominant disorder with incomplete penetrance characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, pulmonary stenosis or atresia, absent pulmonary valve, right aortic arch, double aortic arch, and major aortopulmonary collateral arteries.
Congenital heart defects, multiple types, 8, with or without heterotaxy
An autosomal dominant disorder characterized by congenital developmental abnormalities involving structures of the heart. Common CHTD8 features include double-outlet right ventricle, unbalanced complete atrioventricular canal, and valvular anomalies. Vascular anomalies include dextroposition of the great arteries, anomalous pulmonary venous return, and superior vena cava to left atrium defect. Patients may also exhibit laterality defects, including dextrocardia, atrial isomerism, dextrogastria, left-sided gallbladder, and intestinal malrotation.
Congenital hemidysplasia with ichthyosiform erythroderma and limb defects
An X-linked dominant disorder of lipid metabolism with disturbed cholesterol biosynthesis, which typically results in male lethality. Clinically, it is characterized by congenital, unilateral, ichthyosisform erythroderma with striking lateralization, sharp midline demarcation, and ipsilateral limb defects and hypoplasia of the body. Limbs defects range from hypoplasia of digits or ribs to complete amelia, often including scoliosis.
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
An autosomal dominant neurodevelopmental syndrome characterized by severe global developmental delay, impaired intellectual development, poor or absent language, significant motor disability with inability to walk, dysmorphic facial features, skeletal anomalies, and variable congenital malformations. Most patients also have seizures and structural brain abnormalities.
Congenital insensitivity to pain with anhidrosis
Hereditary sensory and autonomic neuropathy IV
Neuropathy, congenital sensory, with anhidrosis
Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and intellectual disability. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.
Autosomal recessive, rare and severe gastrointestinal disorder. It is characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. An almost total lack of LCT activity is found in jejunal biopsy material of patients with congenital lactase deficiency. Opposite to congenital lactase deficiency, also known as lactose intolerance, is the most common enzyme deficiency worldwide. It is caused by developmental down-regulation of lactase activity during childhood or early adulthood. The decline of lactase activity is a normal physiological phenomenon; however, the majority of Northern Europeans have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). The down-regulation of lactase activity operates at the transcriptional level and it is associated with a noncoding variation in the MCM6 gene, located in the upstream vicinity of LCT.
Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi
Congenital lipomatous overgrowth vascular malformations epidermal nevi and skeletal/spinal abnormalities
A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth.
Congenital myopathy with excess of muscle spindles
Congenital short bowel and malrotation syndrome
A disease characterized by a shortened small intestine, intestinal malrotation, and malabsorption. The mean length of the small intestine in CSBS patients is approximately 50 cm, compared with a normal length at birth of 190-280 cm. Patients with CSBS may develop severe malnutrition as a result of the hugely reduced absorptive surface of the small intestine. Infants require parenteral nutrition for survival. However, parenteral nutrition itself causes life-threatening complications such as sepsis and liver failure which are associated with a high rate of mortality early in life.
Congenital short bowel syndrome, X-linked
A disease characterized by a shortened small intestine, and malabsorption. The mean length of the small intestine in affected individuals is approximately 50 cm, compared with a normal length at birth of 190-280 cm. It is associated with significant mortality and morbidity. Infants usually present with failure to thrive, recurrent vomiting, and diarrhea.
Congenital sucrase-isomaltase deficiency
Autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI.
Congenital systemic glutamine deficiency
Glutamine synthase deficiency, congenital systemic
Rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid.
A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle.
An autosomal dominant connective tissue disorder characterized by contractures, arachnodactyly, scoliosis, and crumpled ears.
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A
Multiple pterygium syndrome, autosomal dominant
Pterygium syndrome, multiple, autosomal dominant
An autosomal dominant disease characterized by contractures of proximal and distal joints, pterygia involving the neck, axillae, elbows, and/or knees, as well as variable vertebral, carpal, and tarsal fusions and short stature. Progression of vertebral fusions has been observed, and inter- and intrafamilial variability has been reported.
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B
An autosomal recessive disease characterized by contractures affecting proximal and distal joints, vertebral fusions and scoliosis, carpal and tarsal fusions as well as webbing of the skin (pterygium) involving the neck, elbows, fingers, and/or knees. Other features include facial dysmorphism, short neck, and absent finger flexion creases. Inter- and intrafamilial variability has been observed.
Convulsions, familial infantile, with paroxysmal choreoathetosis
Familial infantile convulsions and paroxysmal choreoathetosis
ICCA syndrome paroxysmal kinesigenic dyskinesia with infantile convulsions
A syndrome characterized by clinical features of benign familial infantile seizures and episodic kinesigenic dyskinesia. Benign familial infantile seizures is a disorder characterized by afebrile seizures occurring during the first year of life, without neurologic sequelae. Paroxysmal choreoathetosis is a disorder of involuntary movements characterized by attacks that occur spontaneously or are induced by a variety of stimuli.
A severe form of cornea plana, a rare ocular disorder characterized by flattened corneal curvature leading to a decrease in refraction, reduced visual activity, hyperopia, hazy corneal limbus, opacities in the corneal parenchyma, and marked arcus senilis often detected at an early age. CNA2 patients manifest extreme hyperopia and additional ocular anomalies such as malformations of the iris, a slit-like pupil, and adhesions between iris and cornea.
Corneal dystrophy and perceptive deafness
Corneal dystrophy and sensorineural deafness
Corneal endothelial dystrophy and perceptive deafness
An ocular disease characterized by the association of corneal clouding with progressive perceptive hearing loss.
Combined granular-lattice corneal dystrophy
A corneal disease resulting in reduced visual acuity and characterized by gray, crumb-like granular deposits in the anterior third of the stroma in each corneal button. Fusiform amyloid deposits, histochemically and morphologically identical to those of lattice corneal dystrophy, are found in the deeper stroma. Additional features include recurrent corneal erosions, and glare and decreased night vision.
A corneal dystrophy characterized by congenital corneal opacification consisting of a large number of flakes and spots throughout all layers of the stroma. It results in progressive, painless visual loss. Corneal erosions and photophobia are absent.
Corneal dystrophy, epithelial basement membrane
Anterior basement membrane corneal dystrophy
Map-dot-fingerprint type corneal dystrophy
A bilateral anterior corneal dystrophy characterized by grayish epithelial fingerprint lines, geographic map-like lines, and dots (or microcysts) on slit-lamp examination. Pathologic studies show abnormal, redundant basement membrane and intraepithelial lacunae filled with cellular debris.
Corneal dystrophy Francois-Neetens speckled or flecked
A form of stromal corneal dystrophy characterized by numerous small white flecks scattered in all levels of the stroma, with configurations varying from semicircular to wreath-like, curvilinear, or punctate. Although CFD may occasionally cause mild photophobia, patients are typically asymptomatic and have normal vision.
Corneal dystrophy Fuchs endothelial early-onset
A corneal disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition.
Fuchs endothelial corneal dystrophy, late-onset
A late-onset form of Fuchs endothelial corneal dystrophy, a disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition.
Corneal dystrophy Fuchs endothelial late-onset
A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. GDLD is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness. Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia, and foreign-body sensation. By the third decade, raised, yellowish-gray, gelatinous masses severely impair visual acuity.
A rare form of stromal corneal dystrophy characterized by multiple small deposits in the superficial central corneal stroma, and progressive visual impairment.
A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. CDL1 is characterized by progressive visual impairment, and the presence of delicate, double-contoured, interdigitating, elongated deposits that form a reticular pattern in the corneal stroma. Systemic amyloidosis is absent. Recurrent corneal ulceration sometimes occurs.
A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. CDL3A is characterized by decreased visual acuity, and the presence of thick, ropy branching lattice lines and accumulations of amyloid deposits in the corneal stroma. Systemic amyloidosis is absent. CDL3A clinically resembles to lattice corneal dystrophy type 3, but differs in that its age of onset is 70 to 90 years. It has an autosomal dominant inheritance pattern.
Juvenile epithelial corneal dystrophy of Meesmann
A form of Meesmann corneal dystrophy, a corneal disease characterized by fragility of the anterior corneal epithelium. Histological examination shows a disorganized and thickened epithelium with widespread cytoplasmic vacuolation and numerous small, round, debris-laden intraepithelial cysts. Patients are usually asymptomatic until adulthood when rupture of the corneal microcysts may cause erosions, producing clinical symptoms such as photophobia, contact lens intolerance and intermittent diminution of visual acuity. Rarely, subepithelial scarring causes irregular corneal astigmatism and permanent visual impairment. MECD1 inheritance is autosomal dominant.
A form of Meesmann corneal dystrophy, a corneal disease characterized by fragility of the anterior corneal epithelium. Histological examination shows a disorganized and thickened epithelium with widespread cytoplasmic vacuolation and numerous small, round, debris-laden intraepithelial cysts. Patients are usually asymptomatic until adulthood when rupture of the corneal microcysts may cause erosions, producing clinical symptoms such as photophobia, contact lens intolerance and intermittent diminution of visual acuity. Rarely, subepithelial scarring causes irregular corneal astigmatism and permanent visual impairment. MECD2 inheritance is autosomal dominant.
Corneal dystrophy, posterior polymorphous, 1
Corneal endothelial dystrophy 1, autosomal dominant
Hereditary polymorphous posterior corneal dystrophy
A rare corneal disorder characterized by small aggregates of apparent vesicles bordered by a gray haze at the level of Descemet membrane, an altered corneal endothelial cell structure, and an unusual proliferation of endothelial cells. Symptoms can range from very aggressive to asymptomatic and non-progressive, even within the same family.
Corneal dystrophy, posterior polymorphous, 2
A rare mild subtype of posterior corneal dystrophy characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit-lamp examination and specular microscopy. Affected patient typically are asymptomatic.
Corneal dystrophy, posterior polymorphous, 3
A subtype of posterior corneal dystrophy, a disease characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit-lamp examination and specular microscopy. Affected patient typically are asymptomatic.
Corneal dystrophy, posterior polymorphous, 4
A subtype of posterior corneal dystrophy, a disease characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit-lamp examination and specular microscopy. In severe cases, corneal endothelial failure may occur and corneal transplantation is required to restore vision. Secondary complications are common and include corneal edema, glaucoma, iris adherence to the cornea, and corectopia. PPCD4 transmission pattern is consistent with autosomal dominant inheritance.
Corneal dystrophy, punctiform and polychromatic pre-Descemet
An autosomal dominant corneal dystrophy characterized by the presence of punctiform, multicolored opacities in the posterior stroma, immediately anterior to Descemet membrane. Affected individuals are typically asymptomatic.
Corneal dystrophy of Bowman layer type I
A bilateral disorder of the cornea characterized by intermittent attacks of ocular irritation, recurrent painful corneal erosions starting in childhood, corneal opacities in a geographic pattern at the level of the Bowman layer, and a progressive decrease of visual acuity. The lesions are primarily in Bowman membrane with secondary involvement of the epithelium and superficial part of the stroma. Bowman membrane is almost completely replaced by pathologic materials including disoriented collagen fibrils.
A form of stromal corneal dystrophy characterized by corneal clouding, resulting from abnormal deposition of cholesterol and phospholipids, and decreased visual acuity. Typically, ring-shaped yellow-white opacities composed of innumerable fine needle-shaped crystals form in Bowman layer and the adjacent anterior stroma of the central cornea. The crystals usually remain in the anterior third of the cornea. The corneal epithelium and endothelium as well as Descemet membrane are spared.
Corneal dystrophy of Bowman layer type II
A bilateral disorder of the cornea characterized by progressive honeycomb-like, subepithelial corneal opacities with recurrent erosions.
Congenital hereditary endothelial corneal dystrophy
Congenital hereditary endothelial dystrophy of cornea
Corneal endothelial dystrophy 2, autosomal recessive
A congenital corneal dystrophy characterized by thickening and opacification of the cornea, altered morphology of the endothelium, and secretion of an abnormal collagenous layer at the Descemet membrane.
A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies.
Cornelia de Lange syndrome 3 with or without midline brain defects
A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome type 3 is a mild form with absence of major structural anomalies. The phenotype in some instances approaches that of apparently non-syndromic intellectual disability.
Cornelia de Lange syndrome 4 with or without midline brain defects
A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies.
A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction.
Coronary artery disease, autosomal dominant, 1
Coronary artery disease with myocardial infarction
Coronary artery disease, autosomal dominant, 2
A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries.
Cortical dysplasia, complex, with other brain malformations 1
A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe intellectual disability, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved.
Cortical dysplasia, complex, with other brain malformations 10
An autosomal recessive disorder of aberrant neuronal migration during brain development. CDCBM10 is clinically characterized by onset in infancy of global developmental delay, impaired intellectual development, seizures, inability to ambulate, and absent language. Brain imaging shows lissencephaly, cortical dysplasia, subcortical heterotopia, and paucity of white matter.
Cortical dysplasia, complex, with other brain malformations 11
An autosomal recessive disorder of aberrant neuronal migration during brain development. CDCBM11 is characterized by dilated ventricles and reduced white matter, and is associated with axonal developmental defects.
Cortical dysplasia, complex, with other brain malformations 2
A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include intrauterine growth retardation, fetal akinesia, seizures, microcephaly, lack of psychomotor development, and arthrogryposis. Brain imaging shows malformations of cortical development, including polymicrogyria, gyral simplification, and thin corpus callosum.
Cortical dysplasia, complex, with other brain malformations 3
A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include early-onset epilepsy, and various malformations of cortical development such as agyria, posterior or frontal pachygyria, subcortical band heterotopia, and thin corpus callosum.
Cortical dysplasia, complex, with other brain malformations 4
A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include early-onset seizures, microcephaly, spastic tetraplegia, and various malformations of cortical development, such as agyria, posterior or frontal pachygyria, thick cortex, and subcortical band heterotopia and thin corpus callosum in some patients.
Cortical dysplasia, complex, with other brain malformations 5
A disorder of aberrant neuronal migration and disturbed axonal guidance. Clinical features include seizures, global developmental delay, and various brain malformations such as a diffuse simplified gyral pattern with reduced volume of white matter, globular basal ganglia, thin and dysmorphic corpus callosum, mild brainstem hypoplasia with a flat pons, mild cerebellar vermis hypoplasia, and mildly enlarged posterior fossa.
Cortical dysplasia, complex, with other brain malformations 6
A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have microcephaly, ataxia, and severe delayed psychomotor development. Brain imaging shows variable malformations of cortical development, including white matter streaks, dysmorphic basal ganglia, corpus callosum abnormalities, brainstem and cerebellar hypoplasia, cortical dysplasia, polymicrogyria.
Cortical dysplasia, complex, with other brain malformations 7
A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization.
Cortical dysplasia, complex, with other brain malformations 9
An autosomal recessive disorder characterized by neurodevelopmental delay apparent from early infancy, acquired microcephaly, hypotonic cerebral palsy, inability to ambulate or speak, and intractable seizures. Brain imaging shows pachygyria with severe cortical gray matter thickening, paucity of gyri without an obvious posterior-anterior gradient or focal dysplasias, hypogenesis of the corpus callosum, and cerebellar hypoplasia.
Cortical dysplasia-focal epilepsy syndrome
A disease characterized by cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures begin in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and intellectual disability develop.
A disease in which affected individuals develop seizures, sometimes associated with transient visual changes. Brain MRI shows both pachygyria and polymicrogyria restricted to the lateral occipital lobes.
Corticosteroid-binding globulin deficiency
Extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo/hypertension and muscle fatigue.
Corticosterone methyloxidase 1 deficiency
Aldosterone deficiency due to defect in 18-hydroxylase
Autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal.
Corticosterone methyloxidase 2 deficiency
Autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum.
An autosomal recessive error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic-pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and infertility in females and premature pseudopuberty in males.
An autosomal dominant error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic- pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo- amenorrhea, and infertility in females and premature pseudopuberty in males.
A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.
A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement.
Craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature
Defined as pelviscapular dysplasia with epiphyseal abnormalities, congenital dwarfism and facial dysmorphy (frontal bossing, hypertelorism, narrow palpebral fissures, deep set globes, strabismus, low-set posteriory rotated and unusually formed external ears, dysplasia of conchae, small chin, short neck with redundant skin folds, and a low hairline). Intelligence may vary from normal to moderately impaired. Radiographic features comprise aplasia of the body of the scapula, hypoplasia of the iliac bone, humeroradial synosthosis, dislocation of the femoral heads, and moderate brachydactyly.
Macrocephaly multiple lipomas and hemangiomata
Macrocephaly pseudopapilledema and multiple hemangiomata
An autosomal dominant hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. CWS7 inheritance is autosomal dominant.
Craniodiaphyseal dysplasia autosomal dominant
A severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine faces) and the bone deposition results in progressive stenosis of craniofacial foramina. Respiratory obstruction due to choanal stenosis compromises the clinical outcomes of affected patients.
A disorder characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include dolichocephaly (with or without sagittal suture synostosis), scaphocephaly, short stature, limb shortening, short ribs, narrow chest, brachydactyly, renal failure and hepatic fibrosis, small and abnormally shaped teeth, sparse hair, skin laxity and abnormal nails.
A disorder characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include short stature, dolichocephaly, craniosynostosis, narrow thorax with pectus excavatum, short limbs, brachydactyly, joint laxity, narrow palpebral fissures, telecanthus with hypertelorism, low-set simple ears, everted lower lip, and short neck. Teeth abnormalities include widely spaced, hypoplastic and fused teeth.
A disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described.
Craniofacial anomalies and anterior segment dysgenesis syndrome
A disorder with extremely variable expressivity. Clinical features include wide interpupillary distance, abnormal corneal endothelium, unusual pinnae, partially to completely empty sella turcica, posterior fossa cyst, anterior encephalocele, and/or hydrocephalus.
Craniofacial dysmorphism, skeletal anomalies and impaired intellectual development syndrome 1
An autosomal recessive disorder characterized by craniofacial and skeletal anomalies, associated with intellectual disability. Typical craniofacial dysmorphism include brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represent skeletal anomalies.
Craniofacial dysmorphism, skeletal anomalies and impaired intellectual development syndrome 2
An autosomal recessive disorder characterized by flat face, low-set ears, and cleft lip and palate, as well as costovertebral anomalies including bifid and fused ribs, vertebral segmentation defects, and scoliosis. Intellectual delay can be severe, with absent speech.
An autosomal dominant congenital anomaly characterized by mandibular hypoplasia, microtia, facial and preauricular skin tags, epibulbar dermoids, and lateral oral clefts. Affected individuals also present skeletal and cardiac abnormalities.
Thought to be an autosomal dominant disease which comprises absence or hypoplasia of the nasal bones, hypoplastic maxilla, small and short nose with thin nares, limited movement of the wrist, short palpebral fissures, ulnar deviation of the fingers, hypertelorism and profound sensory-neural deafness.
X-linked inherited syndrome characterized by hypertelorism, coronal synostosis with brachycephaly, downslanting palpebral fissures, clefting of the nasal tip, joint anomalies, longitudinally grooved fingernails and other digital anomalies.
Autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects.
Craniometaphyseal dysplasia, autosomal dominant
Craniometaphyseal dysplasia Jackson type
An osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy.
Craniometaphyseal dysplasia, autosomal recessive
A form of osteoarthropathy characterized by swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature.
A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability.
A primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. CRS2 is characterized by either fronto-orbital recession, or frontal bossing, or turribrachycephaly, or cloverleaf skull. Associated features include severe headache, high incidence of visual problems (myopia or hyperopia), and short first metatarsals. Intelligence is normal.
A form of craniosynostosis, a primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability.
A disorder characterized by craniosynostosis, maxillary hypoplasia, and dental anomalies, including malocclusion, delayed and ectopic tooth eruption, and/or supernumerary teeth. Some patients also display minor digit anomalies, such as syndactyly and/or clinodactyly.
An autosomal recessive, sclerosing bone disorder characterized by proportional or short-limbed short stature in association with macrocephaly, dolichocephaly, or prominent forehead. Radiography shows hyperostosis of the calvaria and skull base, with metadiaphyseal undermodeling of the long tubular bones and mild shortening and diaphyseal broadening of the short tubular bones. Affected individuals experience progressive vision loss in the first decade of life due to optic nerve compression, and deafness may develop in the second decade of life.
Occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected animal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness.
Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive.
Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant.
Crisponi/Cold-induced sweating syndrome 1
Muscle contractions tetanoform with characteristic face camptodactyly hyperthermia and sudden death
An autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Patients manifest, in the neonatal period, orofacial weakness with impaired sucking and swallowing, resulting in poor feeding. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. These features are referred to as Crisponi syndrome and can result in early death in infancy. Patients who survive into childhood have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Additional abnormalities include a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis.
Crisponi/Cold-induced sweating syndrome 2
An autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.
Crouzon syndrome with acanthosis nigricans
Classic Crouzon disease which is caused by mutations in the FGFR2 gene is characterized by craniosynostosis (premature fusion of the skull sutures), and facial hypoplasia. Crouzon syndrome with acanthosis nigricans (a skin disorder characterized by pigmentation anomalies), CAN, is considered to be an independent disorder from classic Crouzon syndrome. CAN is characterized by additional more severe physical manifestation, such as Chiari malformation, hydrocephalus, and atresia or stenosis of the choanas, and is caused by a specific mutation (Ala-391 to Glu) in the transmembrane domain of FGFR3. It is proposed to have an autosomal dominant mode of inheritance.
An autosomal dominant disorder of red cell membrane permeability characterized by cold-induced changes in cell volume, resulting in cold-sensitive stomatocytosis, and increased erythrocyte osmotic fragility and autohemolysis at 4 degrees Celsius. Patients present with mild to moderate hemolytic anemia, splenomegaly, fatigue, and pseudohyperkalemia due to a potassium leak from the erythrocytes.
Cryptophthalmos, unilateral or bilateral, isolated
cryptophthalmos with microphthalmia and Peters anomaly
An autosomal dominant, rare condition characterized by congenital eyelid malformation with an underlying malformed eye. It can be bilateral or unilateral and is classified into complete (typical), incomplete (atypical) and abortive (congenital symblepharon) forms. The skin of patients with complete cryptophthalmos extends uninterrupted from the forehead to the cheek, whereas incomplete cryptophthalmos exists when there is medial eyelid fusion, but coincident intact lateral structures. The symblepharon variety presents with fusion of the upper eyelid skin to the superior aspect of the globe. The complete variety is the most common form.
One of the most frequent congenital abnormalities in humans, involving 2-5% of male births. Cryptorchidism is associated with increased risk of infertility and testicular cancer.
An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia.
The triad of a presacral tumor, sacral agenesis and anorectal malformation constitutes the Currarino syndrome which is caused by dorsal-ventral patterning defects during embryonic development. The syndrome occurs in the majority of patients as an autosomal dominant trait.
Craniofacial malformations, asymmetric, with polysyndactyly and abnormal skin and gut development
A multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas.
Cutaneous telangiectasia and cancer syndrome, familial
A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well.
A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema.
A form of cutis laxa, a connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema. ADCL3 patients manifest thin skin with visible veins and wrinkles, cataract or corneal clouding, moderate intellectual disability, muscular hypotonia with brisk muscle reflexes, clenched fingers, and pre- and postnatal growth retardation.
A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. Type I autosomal recessive cutis laxa is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon.
A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. ARCL1B features include emphysema, lethal pulmonary artery occlusion, aortic aneurysm, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels.
Cutis laxa with congenital disorder of glycosylation
Cutis laxa with growth and developmental delay
Cutis laxa with joint laxity and retarded development
A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Some affected individuals develop seizures and mental deterioration later in life, whereas the skin phenotype tends to become milder with age. At the molecular level, an abnormal glycosylation of serum proteins is observed in many cases.
A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Patients do not manifest metabolic abnormalities.
Cutis laxa autosomal recessive, type IIC
A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. Most ARCL2C patients exhibit severe hypotonia as well as cardiovascular involvement.
Cutis laxa, autosomal recessive, type IID
A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. Most ARCL2D patients exhibit severe hypotonia as well as cardiovascular and neurologic involvement.
Cutis laxa, autosomal recessive, type IIE
A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. ARCL2E patients present with cutis laxa, inguinal hernia, craniofacial dysmorphology, variable heart defects, and prominent skeletal features including craniosynostosis, short stature, brachydactyly, and syndactyly.
Cutis laxa autosomal recessive type IIIA
Developmental delay-choreoathetosis-joint dislocation-lax skin
A syndrome characterized by facial dysmorphism with a progeroid appearance, large and late-closing fontanel, cutis laxa, joint hyperlaxity, athetoid movements and hyperreflexia, pre- and postnatal growth retardation, intellectual deficit, developmental delay, and ophthalmologic abnormalities.
Cutis laxa autosomal recessive type IIIB
A disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa.
A disorder characterized by cyanosis in the fetus and neonate, due to a defect in the fetal hemoglobin chain which has reduced affinity for oxygen. Some patients develop anemia resulting from increased destruction of red cells containing abnormal or unstable hemoglobin. The cyanosis resolves spontaneously by 5 to 6 months of age or earlier, as the adult beta-globin chain is produced and replaces the fetal gamma-globin chain.
Autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.
A disorder characterized by multiple skin tumors that develop from skin appendages, such as hair follicles and sweat glands. Affected individuals typically develop large numbers of tumors called cylindromas that arise predominantly in hairy parts of the body with approximately 90% on the head and neck. In severely affected individuals, cylindromas may combine into a confluent mass which may ulcerate or become infected (turban tumor syndrome). Individuals with familial cylindromatosis occasionally develop other types of tumors including spiradenomas that begin in sweat glands, and trichoepitheliomas arising from hair follicles.
Homocystinuria due to cystathionine beta-synthase deficiency
Homocystinuria with or without response to pyridoxine
Hyperhomocysteinemia thrombotic CBS-related
An enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, intellectual disability, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine.
Autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.
A common generalized disorder of the exocrine glands which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. It is the most common genetic disease in Caucasians, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive.
Cystinosis, adult, non-nephropathic type
A form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. Cystinosis adult non-nephropathic type is characterized by ocular features and a benign course. Patients manifest mild photophobia due to conjunctival and corneal cystine crystals.
Cystinosis, late-onset juvenile or adolescent nephropathic type
A form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. Late-onset juvenile or adolescent nephropathic cystinosis is an intermediated form, manifesting first at age 10 to 12 years with proteinuria due to glomerular damage rather than with the manifestations of tubular damage that occur first in infantile cystinosis. There is no excess amino aciduria and stature is normal. Photophobia, late development of pigmentary retinopathy, and chronic headaches are features.
Defect of lysosomal cystine transport protein
A form of cystinosis, a lysosomal storage disease due to defective transport of cystine across the lysosomal membrane. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. The classical nephropathic form has onset in the first year of life and is characterized by a polyuro-polydipsic syndrome, marked height-weight growth delay, generalized impaired proximal tubular reabsorptive capacity, with severe fluid-electrolyte balance alterations, renal failure, ocular symptoms and other systemic complications.
An autosomal disorder characterized by impaired epithelial cell transport of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the proximal renal tubule and gastrointestinal tract. The impaired renal reabsorption of cystine and its low solubility causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis, and, rarely, renal failure.
Pseudorheumatoid dysplasia progressive with hypoplastic toes
Spondyloepiphyseal dysplasia with precocious osteoarthritis
A skeletal dysplasia characterized by early-onset, progressive pseudorheumatoid arthritis, platyspondyly, and short third and fourth toes.
A rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.
A neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.
Disorder of peroxisomal fatty acid beta-oxidation.
A rare metabolic disease characterized by chronic metabolic acidosis and a highly variable clinical phenotype. Clinical features range from an encephalopathic presentation with seizures, microcephaly, severe intellectual disability and early death, to milder manifestations with only speech delay or even normal development.
An autosomal recessive metabolic disorder characterized by D-lactic aciduria in the presence of normal plasma lactic acid.
Lysosomal glycogen storage disease without acid maltase deficiency
Vacuolar cardiomyopathy and myopathy X-linked
DAND is a lysosomal glycogen storage disease characterized by the clinical triad of cardiomyopathy, vacuolar myopathy and intellectual disability. It is often associated with an accumulation of glycogen in muscle and lysosomes.
A skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp and forehead), palmoplantar pits and distinctive nail abnormalities. It is due to loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Patients with mild disease may have no more than a few scattered keratotic papules or subtle nail changes, whereas those with severe disease are handicapped by widespread malodorous keratotic plaques. Some patients present with hemorrhage into acantholytic vesicles on the palms and dorsal aspects of the fingers which gives rise to black macules. In a few families affected by Darier disease, neuropsychiatric abnormalities such as mild intellectual disability, schizophrenia, bipolar disorder and epilepsy have been reported. Stress, UV exposure, heat, sweat, friction and oral contraception exacerbate disease symptoms. Clinical variants of Darier disease include hypertrophic, vesicobullous, hypopigmented, cornifying, zosteriform or linear, acute and comedonal subtypes. Comedonal Darier disease is characterized by the coexistence of acne-like comedonal lesions with typical Darier hyperkeratotic papules on light-exposed areas. At histopathologic level, comedonal Darier disease differs from classic Darier disease in the prominent follicular involvement and the presence of greatly elongated dermal villi.
Xerodermic idiocy of de Sanctis and Cacchione
An autosomal recessive syndrome consisting of xeroderma pigmentosum associated with severe neurological and developmental involvement. In addition to the clinical signs of xeroderma pigmentosum, patients present with intellectual disability, dwarfism, gonadal hypoplasia, microcephaly and various neurologic complications of early onset.
An autosomal recessive disorder characterized by prelingual sensorineural hearing loss associated with high myopia.
Deafness with labyrinthine aplasia, microtia and microdontia
Congenital deafness with inner ear agenesis, microtia and microdontia
Unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia).
A form of sensorineural deafness characterized by moderate-to-profound hearing loss and mitochondrial inheritance. It is induced by exposure to aminoglycosides.
Deafness, autosomal dominant 1, with or without thrombocytopenia
Hereditary low-frequency sensorineural hearing loss
Non-syndromic neurosensory deafness autosomal dominant type 1
Non-syndromic sensorineural deafness autosomal dominant type 1
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Patients may have mild thrombocytopenia and enlarged platelets, although most of DFNA1 affected individuals do not have significant bleeding tendencies.
Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy
An autosomal dominant sensorineural deafness associated with hypertrophic cardiomyopathy.
Non-syndromic neurosensory deafness autosomal dominant type 10
Non-syndromic sensorineural deafness autosomal dominant type 10
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Non-syndromic sensorineural deafness autosomal dominant type 11
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA11 is characterized by onset after complete speech acquisition and subsequent gradual progression.
Non-syndromic sensorineural deafness autosomal dominant type 12
Non-syndromic neurosensory deafness autosomal dominant type 13
Non-syndromic sensorineural deafness autosomal dominant type 13
A form of non-syndromic hearing loss with variable phenotype in terms of age at onset, levels of progression, and shape of audiograms.
A form of deafness characterized by progressive high frequency hearing impairment and cochleosaccular degeneration.
Non-syndromic neurosensory deafness autosomal dominant type 20
Non-syndromic sensorineural deafness autosomal dominant type 20
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA21 is an autosomal dominant, progressive form with incomplete penetrance. Age at onset ranges from infancy to late adulthood.
Non-syndromic neurosensory deafness autosomal dominant type 22
Non-syndromic sensorineural deafness autosomal dominant type 22
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA22 is progressive and postlingual, with onset during childhood. By the age of approximately 50 years, affected individuals invariably have profound sensorineural deafness.
A form of non-syndromic deafness characterized by prelingual, bilateral, symmetric hearing loss with a conductive component present in some but not all patients.
Non-syndromic neurosensory deafness autosomal dominant type 25
Non-syndromic sensorineural deafness autosomal dominant type 25
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA25 expression is variable in terms of onset and rate of progression, with an age-dependent penetrance resembling an early-onset presbycusis, or senile deafness, a progressive bilateral loss of hearing that occurs in the aged.
A form of non-syndromic deafness characterized by postlingual, progressive, moderate to profound sensorineural hearing loss.
Non-syndromic neurosensory deafness autosomal dominant type 28
Non-syndromic sensorineural deafness autosomal dominant type 28
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA28 is characterized by mild to moderate hearing loss across most frequencies that progresses to severe loss in the higher frequencies by the fifth decade.
Non-syndromic neurosensory deafness autosomal dominant type 2A
Non-syndromic sensorineural deafness autosomal dominant type 2A
A form of non-syndromic sensorineural deafness characterized by progressive high frequency hearing loss in adulthood, with milder expression in females.
Deafness, autosomal dominant, 34, with or without inflammation
A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations.
Non-syndromic neurosensory deafness autosomal dominant type 36
Non-syndromic sensorineural deafness autosomal dominant type 36
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA36 is a bilateral hearing loss, and begins at 5-10 years of age. It progresses to profound deafness within 10-15 years.
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA37 is a slowly progressive, postlingual form.
Deafness, autosomal dominant, 39, with dentinogenesis imperfecta 1
DFNA39/dentinogenesis imperfecta 1 syndrome
A disorder characterized by the association of progressive sensorineural high-frequency hearing loss with dentinogenesis imperfecta.
Non-syndromic neurosensory deafness autosomal dominant type 3A
Non-syndromic sensorineural deafness autosomal dominant type 3A
Non-syndromic neurosensory deafness autosomal dominant type 3B
Non-syndromic sensorineural deafness autosomal dominant type 3B
A form of non-syndromic sensorineural hearing loss characterized by a variable phenotype, ranging from bilateral middle to high frequency hearing loss to profound sensorineural deafness. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies.
A form of non-syndromic deafness characterized by initially moderate hearing loss that affects mainly low to mid frequencies. Later, it progresses to involve all the frequencies and leads to a profound hearing loss by the 6th decade.
Deafness autosomal dominant due to mutation in MYO1A
Non-syndromic neurosensory deafness autosomal dominant type 48
Non-syndromic sensorineural deafness autosomal dominant type 48
Non-syndromic neurosensory deafness autosomal dominant type 4
Non-syndromic sensorineural deafness autosomal dominant type 4
Non-syndromic neurosensory deafness autosomal dominant type 5
Non-syndromic sensorineural deafness autosomal dominant type 5
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA56 is characterized by progressive hearing impairment with postlingual onset.
Non-syndromic neurosensory deafness autosomal dominant type 6
Non-syndromic sensorineural deafness autosomal dominant type 6
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA6 is a low-frequency hearing loss in which frequencies of 2000 Hz and below are predominantly affected. Many patients have tinnitus, but there are otherwise no associated features such as vertigo. Because high-frequency hearing is generally preserved, patients retain excellent understanding of speech, although presbycusis or noise exposure may cause high-frequency loss later in life. DFNA6 worsens over time without progressing to profound deafness.
Non-syndromic neurosensory deafness autosomal dominant type 64
Non-syndromic sensorineural deafness autosomal dominant type 64
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA65 is characterized by postlingual onset of slowly progressive hearing loss in the third decade. Initially affecting the high frequencies, the hearing loss eventually affects all frequencies and results in severe to profound deafness in the seventh decade. Vestibular function is normal.
A form of non-syndromic sensorineural hearing loss with postlingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA7 is a progressive form with highly variable age at onset and severity, even within families. The age at onset ranges from congenital to mid-adulthood.
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA70 is characterized by slowly progressive, postlingual hearing impairment.
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA71 is characterized by bilateral mild to moderate hearing loss before age 20 years, which gradually progresses to severe to profound hearing loss.
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA72 primarily affects the middle frequencies. It gradually progresses to whole-frequency hearing loss.
A form of non-syndromic hearing loss characterized by mild to severe bilateral symptoms with variable age of onset from early childhood to the third decade.
A form of non-syndromic deafness characterized by progressive, postlingual hearing loss with onset in the third decade of life.
A form of non-syndromic deafness characterized by late-onset hearing loss that involves mid and high frequencies, and progresses to encompass all frequencies.
A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss and variable age at onset. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by adult onset of bilateral, postlingual, mild-to-severe sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by congenital, profound bilateral sensorineural hearing loss affecting all frequencies. Some patients may have mild motor delay early in life due to vestibular dysfunction. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic, progressive sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA79 affected females appear to have milder hearing loss than males.
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA80 is characterized by severe inner ear malformations, bilateral cochlear aplasia and absent eighth cranial nerve.
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DNFA81 is characterized by postlingual onset of slowly progressive deafness.
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DNFA82 is characterized by onset of rapidly progressive bilateral sensorineural hearing loss usually early in the first decade.
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DNFA83 is characterized by progressive, mild to profound hearing loss.
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA84 is characterized by slowly progressive, postlingual hearing loss.
A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA85 is characterized by progressive hearing loss, with onset in childhood or young adulthood.
A form of non-syndromic hearing loss characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Hearing loss is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers.
Deafness, autosomal dominant, without vestibular involvement
A form of non-syndromic, sensorineural deafness characterized by prelingual hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by bilateral, moderate to severe hearing loss. Vestibular function is unaffected.
A form of non-syndromic deafness characterized by profound hearing loss affecting all frequencies. Vestibular function is unaffected.
A form of sensorineural deafness with onset in early childhood. Hearing impairment progresses from mild to severe or even profound before the second decade, and is accompanied by vestibular areflexia.
A form of non-syndromic, sensorineural deafness characterized by bilateral, congenital, severe to profound hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB109 affected individuals additionally exhibit vestibular dysplasia, although they do not manifest problems with balance or movement.
A form of non-syndromic, sensorineural deafness characterized by prelingual hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB110 affected individuals additionally exhibit mild, age-dependent vestibular dysfunction.
A form of non-syndromic, sensorineural deafness characterized by early-onset, moderate to severe hearing loss with no vestibular involvement. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic, sensorineural deafness characterized by postlingual progressive hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by congenital profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by severe sensorineural hearing impairment in early childhood. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by slowly progressive, moderate to profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by pre-lingual, moderate-to-profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, autosomal recessive, 118, with cochlear aplasia
A form of non-syndromic deafness characterized by congenital profound sensorineural hearing loss and cochlear aplasia. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Congenital neurosensory deafness autosomal recessive 12
Non-syndromic neurosensory deafness autosomal recessive type 12
Non-syndromic sensorineural deafness autosomal recessive type 12
Non-syndromic neurosensory deafness autosomal recessive type 15
Non-syndromic sensorineural deafness autosomal recessive type 15
A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Non-syndromic neurosensory deafness autosomal recessive type 16
Non-syndromic sensorineural deafness autosomal recessive type 16
Non-syndromic neurosensory deafness autosomal recessive type 18
Non-syndromic sensorineural deafness autosomal recessive type 18
A form of non-syndromic deafness characterized by a moderate hearing impairment, which can be associated with vestibular dysfunction, and a flat to shallow 'U' or slightly downsloping shaped audiograms.
Deafness neurosensory autosomal recessive 1
Non-syndromic neurosensory deafness autosomal recessive type 1
Non-syndromic sensorineural deafness autosomal recessive type 1
Deafness neurosensory autosomal recessive 2
Neurosensory nonsyndromic recessive deafness 2
Non-syndromic neurosensory deafness autosomal recessive type 2
Non-syndromic sensorineural deafness autosomal recessive type 2
Non-syndromic neurosensory deafness autosomal recessive type 21
Non-syndromic sensorineural deafness autosomal recessive type 21
Non-syndromic neurosensory deafness autosomal recessive type 22
Non-syndromic sensorineural deafness autosomal recessive type 22
Non-syndromic neurosensory deafness autosomal recessive type 23
Non-syndromic sensorineural deafness autosomal recessive type 23
A form of non-syndromic sensorineural deafness characterized by moderate to severe or profound hearing loss which is progressive in some individuals but not in others. Speech development is impaired in some but not all affected individuals, and vestibular dysfunction is observed in some affected individuals. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic sensorineural deafness characterized by prelingual, severe to profound hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Non-syndromic neurosensory deafness autosomal recessive type 28
Non-syndromic sensorineural deafness autosomal recessive type 28
Non-syndromic neurosensory deafness autosomal recessive type 29
Non-syndromic sensorineural deafness autosomal recessive type 29
Deafness neurosensory autosomal recessive 3
Neurosensory nonsyndromic recessive deafness 3
Non-syndromic neurosensory deafness autosomal recessive type 3
Non-syndromic sensorineural deafness autosomal recessive type 3
A form of non-syndromic deafness characterized by bilateral progressive hearing loss, which first affects the high frequencies. Hearing loss begins in the second decade, and by age 50 is severe in high and middle frequencies and moderate at low frequencies.
Non-syndromic neurosensory deafness autosomal recessive type 31
Non-syndromic sensorineural deafness autosomal recessive type 31
Deafness, autosomal recessive, 32, with or without immotile sperm
Hearing impairment and infertile male syndrome
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB32 is characterized by prelingual, progressive, moderate to profound sensorineural deafness. Some affected men are infertile.
A form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss.
Deafness, autosomal recessive, 36, with or without vestibular involvement
Non-syndromic neurosensory deafness autosomal recessive type 36
Non-syndromic sensorineural deafness autosomal recessive type 36
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB36 is characterized by prelingual, profound hearing loss, and vestibular areflexia in some patients.
Congenital neurosensory deafness autosomal recessive 37
Non-syndromic neurosensory deafness autosomal recessive type 37
Non-syndromic sensorineural deafness autosomal recessive type 37
Congenital neurosensory deafness autosomal recessive 39
Non-syndromic neurosensory deafness autosomal recessive type 39
Non-syndromic sensorineural deafness autosomal recessive type 39
A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness neurosensory autosomal recessive 4
Neurosensory nonsyndromic recessive deafness 4
Non-syndromic neurosensory deafness autosomal recessive type 4
Non-syndromic sensorineural deafness autosomal recessive type 4
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB4 is associated with an enlarged vestibular aqueduct.
Congenital neurosensory deafness autosomal recessive 42
Non-syndromic neurosensory deafness autosomal recessive type 42
Non-syndromic sensorineural deafness autosomal recessive type 42
A prelingual, non-progressive form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies.
Non-syndromic neurosensory deafness autosomal recessive type 48
Non-syndromic sensorineural deafness autosomal recessive type 48
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB48 patients have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies.
Non-syndromic neurosensory deafness autosomal recessive type 49
Non-syndromic sensorineural deafness autosomal recessive type 49
Non-syndromic neurosensory deafness autosomal recessive type 53
Non-syndromic sensorineural deafness autosomal recessive type 53
A form of non-syndromic sensorineural deafness characterized by prelingual, profound, non-progressive hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic, sensorineural deafness characterized by symmetric, bilateral hearing loss with onset in early childhood. Vestibular function is preserved. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB57 severity ranges from moderate to severe.
A form of sensorineural hearing impairment with absent or severely abnormal auditory brainstem response but normal otoacoustic emissions (auditory neuropathy or auditory dys-synchrony). Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem.
Deafness neurosensory autosomal recessive 6
Neurosensory nonsyndromic recessive deafness 6
Non-syndromic neurosensory deafness autosomal recessive type 6
Non-syndromic sensorineural deafness autosomal recessive type 6
Non-syndromic neurosensory deafness autosomal recessive type 61
Non-syndromic sensorineural deafness autosomal recessive type 61
Non-syndromic neurosensory deafness autosomal recessive type 63
Non-syndromic sensorineural deafness autosomal recessive type 63
Deafness neurosensory autosomal recessive 11
Deafness neurosensory autosomal recessive 7
Non-syndromic neurosensory deafness autosomal recessive type 7
Non-syndromic sensorineural deafness autosomal recessive type 7
Deafness, autosomal recessive, 70, with or without adult-onset neurodegeneration
A form of non-syndromic deafness characterized by severe, bilateral hearing impairment with prelingual onset, resulting in inability to acquire normal speech. Affected individuals may develop a neurodegenerative disease in adulthood, including ataxia with loss of ambulation, optic atrophy, dystonia or spasticity, and cognitive decline with psychiatric features.
A form of non-syndromic sensorineural deafness characterized by prelingual, bilateral, profound hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic sensorineural deafness, a disorder resulting from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB76 affected individuals have onset of progressive high frequency hearing impairment between birth and 6 years of age. The hearing loss is severe at high frequencies by adulthood.
Non-syndromic neurosensory deafness autosomal recessive type 77
A form of non-syndromic deafness characterized by preserved low-frequency hearing, and a trend toward mild to moderate mid-frequency and high-frequency hearing loss during childhood and adolescence. Hearing loss progresses to become moderate to severe at mid and high frequencies during adulthood.
Non-syndromic neurosensory deafness autosomal recessive type 79
A form of non-syndromic deafness characterized by progressive and severe sensorineural hearing loss. There are no symptoms of vestibular dysfunction.
Childhood-onset neurosensory deafness autosomal recessive 8
Deafness neurosensory autosomal recessive 8
Neurosensory nonsyndromic recessive deafness 8
Non-syndromic neurosensory deafness autosomal recessive type 8
Non-syndromic sensorineural deafness autosomal recessive type 8
Deafness autosomal recessive 84A with vestibular dysfunction
Non-syndromic neurosensory deafness autosomal recessive type 84
A form of non-syndromic deafness characterized by progressive, sensorineural hearing loss and vestibular dysfunction.
A form of non-syndromic deafness characterized by congenital, non-progressive, sensorineural, symmetric hearing loss. Vestibular hypofunction is rarely observed.
A form of non-syndromic deafness characterized by prelingual onset of profound sensorineural hearing loss affecting all frequencies.
A form of non-syndromic deafness characterized by prelingual onset of severe to profound mixed conductive and sensorineural hearing loss.
A form of non-syndromic deafness characterized by bilateral, prelingual, moderate to severe hearing loss affecting all frequencies.
Deafness neurosensory autosomal recessive 9
Neurosensory nonsyndromic recessive deafness 9
Non-syndromic neurosensory deafness autosomal recessive type 9
Non-syndromic neurosensory deafness autosomal recessive type 91
A form of non-syndromic deafness characterized by progressive and age-dependent sensorineural hearing loss. Vestibular function is normal.
Non-syndromic neurosensory deafness autosomal recessive type 93
A form of non-syndromic deafness characterized by stable, bilateral, symmetric, prelingual moderate to severe deafness. Hearing impairment is slightly more pronounced in the mid-frequencies, resulting in a distinctive shallow U-shaped audiogram.
A form of non-syndromic, sensorineural deafness characterized by prelingual, profound, bilateral hearing impairment. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A form of non-syndromic deafness characterized by prelingual, bilateral, severe-to-profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Deafness, cataract, impaired intellectual development, and polyneuropathy
An autosomal recessive disease characterized by early onset of deafness, cataract, severe developmental delay, and severely impaired intellectual development. Patients later develop polyneuropathy of the lower extremities, associated with depigmentation of the hair in that area.
Deafness, congenital heart defects, and posterior embryotoxon
An autosomal dominant disease characterized by mild to severe combined hearing loss, congenital heart defects, and posterior embryotoxon, a corneal abnormality consisting of a central collagen core surrounded by a thin layer of Descemets membrane and separated from the anterior chamber by a layer of endothelium. Congenital heart defects include tetralogy of Fallot, ventricular septal defect, or isolated peripheral pulmonic stenosis.
Deafness, congenital, and adult-onset progressive leukoencephalopathy
An autosomal recessive, complex neurodegenerative disorder characterized by congenital sensorineural deafness, and progressive motor and cognitive decline apparent in young adulthood. Brain imaging shows diffuse white matter abnormalities affecting various brain regions, consistent with a progressive leukoencephalopathy. More variable additional features may include visual impairment and axonal peripheral neuropathy. Premature death may occurr in some patients.
Deafness, congenital, unilateral or asymmetric
An autosomal dominant form of non-syndromic, sensorineural deafness characterized by inability to hear affecting one ear. Some patients suffers from asymmetric, bilateral hearing loss.
Deafness, congenital, with onychodystrophy, autosomal dominant
An autosomal dominant syndrome characterized mainly by congenital sensorineural hearing loss accompanied by dystrophic or absent nails. Coniform teeth, selective tooth agenesis, and hands and feet abnormalities are present in some patients.
Deafness, dystonia, and cerebral hypomyelination
An X-linked recessive syndrome characterized by sensorineural deafness, intellectual disability, dysmorphic facial features, dystonia, pyramidal signs, almost no psychomotor development, and hypomyelination on brain imaging.
Deafness, onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome
Brachydactyly due to absence of distal phalanges
A syndrome characterized by sensorineural deafness, intellectual disability, hypoplastic or absent nails, small or absent distal phalanges of hands and feet. Additional features include coarse facies, a large nose with wide nasal bridge, bulbous tip and anteverted nares, a long prominent philtrum and downturned corners of the mouth. Progressive neurological manifestations include seizures from infancy, optic atrophy, and peripheral polyneuropathy.
A form of non-syndromic deafness with maternal inheritance. Affected individuals manifest progressive, postlingual, sensorineural hearing loss involving high frequencies.
Congenital sensorineural deafness X-linked 2
A form of deafness characterized by progressive, severe-to-profound sensorineural hearing loss in males. Females manifest mild to moderate hearing loss.
Deafness 3 conductive with stapes fixation
Deafness conductive with stapes fixation
Deafness mixed with perilymphatic gusher
Deafness mixed with perilymph Gusher X-linked
X-linked mixed conductive and neurosensory deafness
X-linked mixed conductive and sensorineural deafness
A form of deafness characterized by both conductive hearing loss resulting from stapes (perilymphatic gusher) fixation, and progressive sensorineural deafness.
Deafness nonsyndromic sensorineural progressive 6
A non-syndromic form of sensorineural, progressive hearing loss with postlingual onset. In affected males, the auditory impairment affects initially high-frequency hearing. It later evolves to become severe to profound and affects all frequencies. Carrier females manifest moderate hearing impairment in the high frequencies.
Deafness, X-linked, 5, with peripheral neuropathy
Auditory neuropathy, X-linked, 1, with peripheral sensory neuropathy
A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system.
A non-syndromic form of sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
A congenital form of bilateral mixed or conductive hearing loss, which is progressive in some patients. Additional clinical features include ear anomalies and facial dysmorphism with bilateral ptosis.
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNY2 patients show bilateral symmetric hearing loss ranging from mild to severe, with onset in the third to fifth decades of life.
Deafness, sensorineural, and male infertility
Characterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes.
Developmental delay with endocrine, exocrine, autonomic, and hematologic abnormalities
An autosomal recessive disorder characterized by moderate to severe global developmental delay, impaired intellectual development, poor or absent speech, and endocrine, pancreatic exocrine and autonomic dysfunction, as well as hematologic abnormalities. Additional features include facial dysmorphism, seizures, undescended testes, and distal skeletal anomalies. Death in early childhood may occur.
Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, coarse facial features, and abnormalities of the cardiovascular, gastrointestinal, genitourinary and skeletal system. Other common features included anemia or pancytopenia, immunodeficiency and recurrent infections, and sensorineural hearing impairment. Death in childhood may occur.
Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema
Familial pseudohyperkalemia 1 due to red cell leak
An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Patients may also show perinatal edema and pseudohyperkalemia due to loss of potassium from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis.
An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. Erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. Affected individuals typically manifest mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur.
Charcot-Marie-Tooth disease demyelinating type 4F
Hereditary motor and sensory neuropathy III
Hypertrophic neuropathy of Dejerine-Sottas
A severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. Characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome.
A condition defined as the absence of testicular enlargement in boys or breast development in girls at an age that is 2-2.5 SD later than the population mean. DPSL is often familial and is highly heritable, most commonly seen with an autosomal dominant inheritance pattern.
A circadian rhythm sleep disorder characterized by sleep-onset insomnia and difficulty in awakening at the desired time. Patients with DSPS have chronic difficulty in adjusting their sleep-onset and wake-up times to occupational, school, and social activities.
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, hypotonia with delayed or absent walking, bilateral sensorineural deafness, poor or absent speech, and mild to severe intellectual disability. Additional variable features may include spasticity or minor involvement of other organ systems, such as hip dislocation or ventricular septal defect.
Diffuse Lewy body disease with gaze palsy
A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
Nephrolithiasis-hypercalciuria X-linked recessive
An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. DENT1 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia.
An X-linked renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones.
Brachyolmia-amelogenesis imperfecta syndrome
Platyspondyly with amelogenesis imperfecta
A disorder characterized by hypoplastic amelogenesis imperfecta, significant short stature, brachyolmia-like anomalies including platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Dental anomalies include widely spaced, small, yellow teeth, oligodontia, and severely reduced to absent enamel.
Autosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth.
Dentici-Novelli neurodevelopmental syndrome
An autosomal recessive disorder characterized by global developmental delay and impaired intellectual development apparent from infancy. Disease severity is variable. More severely affected individuals have profound intellectual disability, axial hypotonia, peripheral spasticity, prenatal and postnatal microcephaly, early-onset seizures, brain imaging abnormalities, and are unable to walk or speak. Patients with a less severe phenotype may achieve some developmental goals and show less severe intellectual disability.
A dental defect in which both primary and secondary dentitions are affected. The clinical crowns of both permanent and deciduous teeth are of normal shape, form and color in most cases, although they may be slightly opalescent and blue or brown. Teeth may be very mobile and exfoliate spontaneously because of inadequate root formation. On radiographs, the roots are short and may be more pointed than normal. Pulp chambers are usually absent except for a chevron-shaped remnant in the crown. Root canals are usually absent.
Dentin dysplasia 1, with extreme microdontia and misshapen teeth
A complex dental malformation characterized by extreme microdontia, oligodontia, dental shape anomalies affecting both primary and permanent teeth, double permanent-tooth formation, thin enamel, and very short roots with a thin associated alveolar bone, as seen in the spectrum of dentin dysplasia type 1.
A dental defect in which the deciduous teeth are opalescent. The permanent teeth are of normal shape, form, and color in most cases. The root length is normal. On radiographs, the pulp chambers of permanent teeth are obliterated, have a thistle-tube deformity and contain pulp stones.
Dentinogenesis imperfecta, Shields type 2
Dentinogenesis imperfecta Shields type II
Dentinogenesis imperfecta without osteogenesis imperfecta
Opalescent teeth without osteogenesis imperfecta
A form of dentinogenesis imperfecta, an autosomal dominant dentin disorder characterized by amber-brown, opalescent teeth that fracture and shed their enamel during mastication, thereby exposing the dentin to rapid wear. Radiographically, the crown appears bulbous and pulpal obliteration is common. The pulp chambers are initially larger than normal prior and immediately after tooth eruption, and then progressively close down to become almost obliterated by abnormal dentin formation. Roots are short and thin. Both primary and permanent teeth are affected. DGI2 is not associated with osteogenesis imperfecta.
Dentinogenesis imperfecta, Shields type 3
Brandywine type dentinogenesis imperfecta
A form of dentinogenesis imperfecta, an autosomal dominant dentin disorder characterized by amber-brown, opalescent teeth that fracture and shed their enamel during mastication, thereby exposing the dentin to rapid wear. Radiographically, the crown appears bulbous and pulpal obliteration is common. The pulp chambers are initially larger than normal prior and immediately after tooth eruption, and then progressively close down to become almost obliterated by abnormal dentin formation. Roots are short and thin. Both primary and permanent teeth are affected. DGI3 teeth typically manifest multiple periapical radiolucencies. DGI3 is not associated with osteogenesis imperfecta.
Typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic.
Atopic dermatitis is a complex, inflammatory disease with multiple alleles at several loci thought to be involved in the pathogenesis. It commonly begins in infancy or early childhood and is characterized by a chronic relapsing form of skin inflammation, a disturbance of epidermal barrier function that culminates in dry skin, and IgE-mediated sensitization to food and environmental allergens. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee.
A rare ectodermal dysplasia characterized by lifelong persistent reticulate hyperpigmentation, non-cicatricial alopecia, and nail dystrophy. Variable features include adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis.
An autosomal dominant syndrome characterized by developmental delay, hypotonia, behavioral problems, eye abnormalities, constipation, feeding difficulties, seizures and sleep problems. Patients exhibit dysmorphic features, including broad/prominent forehead, synophrys and/or bushy eyebrows, depressed nasal bridge and bulbous nasal tip. Additional variable features are posteriorly rotated ears, hirsutism, deep-set eyes, thin upper lip, inverted nipples, hearing loss and branchial cleft anomalies.
Micromelic dwarfism with vertebral and metaphyseal abnormalities and advanced carpotarsal ossification
A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence or absence of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations.
An autosomal dominant disease characterized by multifocal fibromatosis of the abdominal wall and mesentery. Desmoid tumors can also affect paraspinal muscles, breast, occiput, arms, and lower ribs.
Rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.
Developmental and epileptic encephalopathy 1
Epileptic encephalopathy, early infantile, 1
Infantile epileptic-dyskinetic encephalopathy
Myoclonic epilepsy X-linked with intellectual disability and spasticity
A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Developmental and epileptic encephalopathy 100
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE100 is an autosomal dominant, severe form characterized by global developmental delay and onset of variable types of seizures in the first months or years of life.
Developmental and epileptic encephalopathy 101
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE101 is an autosomal recessive, severe form characterized by onset of seizures in early infancy. Death in infancy may occur.
Developmental and epileptic encephalopathy 102
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE102 is an autosomal recessive form characterized by onset of variable types of seizures in infancy.
Developmental and epileptic encephalopathy 103
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE103 is an autosomal dominant form characterized by onset of various types of seizures in the first year of life.
Developmental and epileptic encephalopathy 104
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE104 is an autosomal dominant form characterized by onset of developmental delay and drug-resistant focal and generalized tonic-clonic seizures in the first few months of life.
Developmental and epileptic encephalopathy 105 with hypopituitarism
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE105 is an autosomal recessive form characterized by onset of seizures in the first weeks or months of life. Affected individuals have hypopituitarism in association with profoundly impaired development with almost no acquisition of skills, brain atrophy, thin corpus callosum, and small pituitary gland.
Developmental and epileptic encephalopathy 106
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE106 is an autosomal recessive form characterized by onset of seizures in the first year of life. Affected individuals have profound global developmental delay, limited ability to move, and severely impaired intellectual development with absent speech. Non-specific brain abnormalities may be observed on MRI.
Developmental and epileptic encephalopathy 107
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE107 is an autosomal recessive form characterized by onset of seizures in the first months of life. Affected individuals have severe global developmental delay, profound intellectual disability, progressive microcephaly, and hypotonia.
Developmental and epileptic encephalopathy 108
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE108 is an autosomal dominant form characterized by the onset of multiple types of seizures in the first 2 years of life.
Developmental and epileptic encephalopathy 109
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE109 is an autosomal dominant form characterized by the onset of various types of seizures in the first months or years of life.
Developmental and epileptic encephalopathy 11
Epileptic encephalopathy, early infantile, 11
An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Developmental and epileptic encephalopathy 110
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE110 is an autosomal recessive form characterized by profound global developmental delay and hypotonia apparent in infancy followed by onset of seizures in the first months or years of life.
Developmental and epileptic encephalopathy 12
Epileptic encephalopathy, early infantile, 12
A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Developmental and epileptic encephalopathy 13
Epileptic encephalopathy, early infantile, 13
A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. DEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy.
Developmental and epileptic encephalopathy 14
Epileptic encephalopathy, early infantile, 14
Malignant migrating partial seizures of infancy
A rare epileptic encephalopathy of infancy that combines pharmacoresistant seizures with developmental delay. This severe neurologic disorder is characterized by onset in the first 6 months of life of refractory focal seizures and arrest of psychomotor development. Ictal EEG shows discharges that arise randomly from various areas of both hemispheres and migrate from one brain region to another.
Developmental and epileptic encephalopathy 15
Epileptic encephalopathy, early infantile, 15
A form of epilepsy that manifests in the neonatal or the early infantile period as severely impaired cognitive and motor development, due to recurrent clinical seizures or prominent interictal epileptiform discharges. Patients develop infantile spasms, mainly of the flexor type, between 3 and 7 months of age, which are accompanied by hypsarrhythmia on EEG. Other features include poor eye contact, hypotonia, primitive reflexes, and irritability. Seizures evolve clinically to Lennox-Gastaut syndrome.
Developmental and epileptic encephalopathy 16
Epileptic encephalopathy, early infantile, 16
A severe autosomal recessive neurologic disorder characterized by onset of seizures in the first weeks or months of life. Seizures can be of various types, are unresponsive to medication, last for long periods of time, and occur frequently. Affected infants show psychomotor regression or lack of psychomotor development, as well as other neurologic features such as extrapyramidal signs and hypotonia. Most die in childhood.
Developmental and epileptic encephalopathy 17
Epileptic encephalopathy, early infantile, 17
A severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements.
Developmental and epileptic encephalopathy 18
Epileptic encephalopathy, early infantile, 18
A severe autosomal recessive neurologic disorder characterized by lack of psychomotor development apparent from birth, dysmorphic facial features, early onset of refractory seizures, and thick corpus callosum and persistent cavum septum pellucidum on brain imaging.
Developmental and epileptic encephalopathy 19
Epileptic encephalopathy, early infantile, 19
A severe neurologic disorder characterized by onset of seizures in the first months of life and usually associated with EEG abnormalities. Affected infants have convulsive seizures (hemiclonic or generalized) that are often prolonged and triggered by fever. Other seizure types include focal, myoclonic, absence seizures, and drop attacks. Development is normal in the first year of life with later slowing and intellectual disability.
Developmental and epileptic encephalopathy 2
Epileptic encephalopathy, early infantile, 2
Rett syndrome early-onset seizure variant
Rett syndrome variant with infantile spasms
A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. However, DEE2 and Rett syndrome are considered two distinct entities.
Developmental and epileptic encephalopathy 21
Epileptic encephalopathy, early infantile, 21
A severe disease characterized by intractable seizures, profound global developmental delay, and persistent severe axial hypotonia as well as appendicular hypertonia.
Developmental and epileptic encephalopathy 23
Epileptic encephalopathy, early infantile, 23
A severe disease characterized by early-onset intractable epilepsy, dysmorphic features, intellectual disability, and cortical blindness. Brain imaging shows an abnormally marked pontobulbar sulcus with mild pontine hypoplasia, white matter abnormalities, and atrophy in the occipital lobe.
Developmental and epileptic encephalopathy 24
Epileptic encephalopathy, early infantile, 24
A disease characterized by early-onset seizures, intellectual disability of varying degrees, and behavioral disturbances or autistic features in most individuals.
Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta
Epileptic encephalopathy, early infantile, 25, with amelogenesis imperfecta
An autosomal recessive disease characterized by subclinical seizures appearing in the first days of life, evolving to severe epileptic disease. Affected individuals have profound or severe delayed development with lack of speech, and most patients do not acquire the ability to sit. Additional variable features include axial hypotonia, peripheral hypertonia, and abnormal involuntary movements such as dystonia and choreoathetosis. Dental abnormalities, including delayed eruption, hypodontia, tooth hypoplasia, yellow discoloration, thin enamel, and enamel chipping are observed in most patients.
Developmental and epileptic encephalopathy 26
Epileptic encephalopathy, early infantile, 26
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE26 patients manifest multiple types of seizures, delayed psychomotor development, poor or absent speech, hypotonia, hypsarrhythmia.
Developmental and epileptic encephalopathy 27
Epileptic encephalopathy, early infantile, 27
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.
Developmental and epileptic encephalopathy 28
Epileptic encephalopathy, early infantile, 28
Developmental and epileptic encephalopathy 29
Epileptic encephalopathy, early infantile, 29
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE29 patients manifest severe infantile epileptic encephalopathy, clubfoot, absent deep tendon reflexes, extrapyramidal symptoms, and persistently deficient myelination.
Developmental and epileptic encephalopathy 3
Epileptic encephalopathy, early infantile, 3
Neonatal epilepsy with suppression-burst pattern
A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. DEE3 is characterized by a very early onset, erratic and fragmentary myoclonus, massive myoclonus, partial motor seizures and late tonic spasms. The prognosis is poor, with no effective treatment, and children with the condition either die within 1 to 2 years after birth or survive in a persistent vegetative state.
Developmental and epileptic encephalopathy 30
Epileptic encephalopathy, early infantile, 30
Developmental and epileptic encephalopathy 31
Epileptic encephalopathy, early infantile, 31
Developmental and epileptic encephalopathy 32
Epileptic encephalopathy, early infantile, 32
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE32 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 33
Epileptic encephalopathy, early infantile, 33
Developmental and epileptic encephalopathy 34
Epileptic encephalopathy, early infantile, 34
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE34 is characterized by onset of refractory migrating focal seizures in infancy. Affected children show developmental regression and are severely impaired globally.
Developmental and epileptic encephalopathy 35
Epileptic encephalopathy, early infantile, 35
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE35 is characterized by onset of seizures in the first months of life associated with essentially no normal development. Many patients die in early childhood.
Developmental and epileptic encephalopathy 36
Congenital disorder of glycosylation type Is
Epileptic encephalopathy, early infantile, 36
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. Some DEE36 patients may present with an abnormal isoelectric focusing of serum transferrin, consistent with a diagnostic classification of congenital disorder of glycosylation type I. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Developmental and epileptic encephalopathy 37
Epileptic encephalopathy, early infantile, 37
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE37 is an autosomal recessive, severe form manifesting in the first years of life. Affected individuals show hyperkinetic movement disorder with choreoathetosis, spasticity, rigidity, intellectual disability, absent speech, and impaired volitional movements.
Developmental and epileptic encephalopathy 38
Epileptic encephalopathy, early infantile, 38
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE38 inheritance is autosomal recessive.
Developmental and epileptic encephalopathy 39 with leukodystrophy
Aspartate-glutamate carrier 1 deficiency
Epileptic encephalopathy, early infantile, 39
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE39 is characterized by global hypomyelination of the central nervous system, with the gray matter appearing relatively unaffected. Inheritance is autosomal recessive.
Developmental and epileptic encephalopathy 4
Epileptic encephalopathy, early infantile, 4
A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have neonatal or infantile onset of seizures, profound intellectual disability, and MRI evidence of brain hypomyelination.
Developmental and epileptic encephalopathy 40
Epileptic encephalopathy, early infantile, 40
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE40 inheritance is autosomal recessive.
Developmental and epileptic encephalopathy 41
Epileptic encephalopathy, early infantile, 41
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE41 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 42
Epileptic encephalopathy, early infantile, 42
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE42 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 43
Epileptic encephalopathy, early infantile, 43
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE43 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 44
Epileptic encephalopathy, early infantile, 44
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE44 transmission pattern is consistent with autosomal recessive inheritance.
Developmental and epileptic encephalopathy 45
Epileptic encephalopathy, early infantile, 45
Developmental and epileptic encephalopathy 46
Epileptic encephalopathy, early infantile, 46
Developmental and epileptic encephalopathy 47
Epileptic encephalopathy, early infantile, 47
Developmental and epileptic encephalopathy 48
Epileptic encephalopathy, early infantile, 48
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE48 is an autosomal recessive form characterized by onset of seizures in the first year of life. Affected individuals manifest global developmental delay, intellectual disability, absent speech, and poor, if any, motor development.
Developmental and epileptic encephalopathy 49
Epileptic encephalopathy, early infantile, 49
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE49 is a severe autosomal recessive form characterized by onset of seizures in the neonatal period, global developmental delay, intellectual disability, and additionally cerebral calcifications and coarse facial features.
Developmental and epileptic encephalopathy 5
Epileptic encephalopathy, early infantile, 5
A disorder characterized by seizures associated with hypsarrhythmia, profound intellectual disability with lack of visual attention and speech development, as well as spastic quadriplegia.
Developmental and epileptic encephalopathy 50
Epileptic encephalopathy, early infantile, 50
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE50 is an autosomal recessive, progressive disease with onset in infancy and favorable response to treatment with oral uridine.
Developmental and epileptic encephalopathy 51
Epileptic encephalopathy, early infantile, 51
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE51 is an autosomal recessive form characterized by onset of intractable seizures and hypotonia in the first days or weeks of life, and severely delayed psychomotor development.
Developmental and epileptic encephalopathy 52
Epileptic encephalopathy, early infantile, 52
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE52 inheritance is autosomal recessive.
Developmental and epileptic encephalopathy 53
Epileptic encephalopathy, early infantile, 53
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE53 inheritance is autosomal recessive.
Developmental and epileptic encephalopathy 54
Epileptic encephalopathy, early infantile, 54
Developmental and epileptic encephalopathy 55
Epileptic encephalopathy, early infantile, 55
Glycosylphosphatidylinositol biosynthesis defect 14
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE55 is an autosomal recessive condition.
Developmental and epileptic encephalopathy 56
Epileptic encephalopathy, early infantile, 56
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE56 is an autosomal dominant condition.
Developmental and epileptic encephalopathy 57
Epileptic encephalopathy, early infantile, 57
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE57 is an autosomal dominant condition.
Developmental and epileptic encephalopathy 58
Epileptic encephalopathy, early infantile, 58
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life.
Developmental and epileptic encephalopathy 59
Epileptic encephalopathy, early infantile, 59
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE59 is an autosomal dominant condition characterized by onset of refractory seizures in early infancy.
Developmental and epileptic encephalopathy 60
Epileptic encephalopathy, early infantile, 60
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE60 is an autosomal recessive condition characterized by onset of seizures in the first months of life.
Developmental and epileptic encephalopathy 61
Epileptic encephalopathy, early infantile, 61
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE61 is an autosomal recessive condition characterized by onset of seizures in infancy.
Developmental and epileptic encephalopathy 62
Epileptic encephalopathy, early infantile, 62
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE62 is characterized by onset of seizures in the first year of life.
Developmental and epileptic encephalopathy 63
Epileptic encephalopathy, early infantile, 63
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE63 is an autosomal recessive disease with onset in infancy.
Developmental and epileptic encephalopathy 64
Epileptic encephalopathy, early infantile, 64
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE64 is an autosomal dominant form characterized by onset of seizures usually in the first year of life. Seizure types are variable and include focal dyscognitive and generalized tonic-clonic seizures, as well as febrile seizures in the mildest affected individuals. Seizures tend to respond to medical treatment.
Developmental and epileptic encephalopathy 65
Epileptic encephalopathy, early infantile, 65
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE65 is an autosomal dominant form characterized by onset of intractable seizures usually in the first 6 months of life and severe to profound psychomotor developmental delay.
Developmental and epileptic encephalopathy 66
Epileptic encephalopathy, early infantile, 66
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE66 is an autosomal dominant form characterized by onset of seizures in first days or weeks of life.
Developmental and epileptic encephalopathy 67
Epileptic encephalopathy, early infantile, 67
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE67 is an autosomal dominant form characterized by onset of seizures in infancy. Later onset of seizures in childhood may occur in some patients.
Developmental and epileptic encephalopathy 68
Epileptic encephalopathy, early infantile, 68
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE68 is an autosomal recessive form characterized by onset of twitching and/or myoclonic jerks in infancy. The disorder progresses to refractory generalized tonic-clonic seizures, often resulting in status epilepticus, loss of developmental milestones, and early death. Other features include delayed development, axial hypotonia, spasticity of the limbs, and clonus.
Developmental and epileptic encephalopathy 69
Epileptic encephalopathy, early infantile, 69
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE69 is an autosomal dominant form characterized by refractory seizures, hypotonia, and profoundly impaired development often associated with macrocephaly, hyperkinetic movements, and contractures. The disorder can sometimes result in early death. Some patients may have a favorable seizure response to topiramate medication.
Developmental and epileptic encephalopathy 6B
Developmental and epileptic encephalopathy 6B, non-Dravet
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE6B is an autosomal dominant condition characterized by onset of seizures in early infancy, profoundly impaired intellectual development, and a hyperkinetic movement disorder.
Developmental and epileptic encephalopathy 7
Epileptic encephalopathy, early infantile, 7
An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities.
Developmental and epileptic encephalopathy 70
Epileptic encephalopathy, early infantile, 70
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE70 is an autosomal dominant form with onset in first months of life and variable severity.
Developmental and epileptic encephalopathy 71
Epileptic encephalopathy, early infantile, 71
Glutaminase deficiency with neonatal epileptic encephalopathy
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE71 is an autosomal recessive form with onset at birth. Death occurs in first weeks of life.
Developmental and epileptic encephalopathy 72
Epileptic encephalopathy, early infantile, 72
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE72 is an autosomal dominant form with variable severity and onset in infancy.
Developmental and epileptic encephalopathy 73
Epileptic encephalopathy, early infantile, 73
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE73 is an autosomal dominant form with onset at birth.
Developmental and epileptic encephalopathy 74
Epileptic encephalopathy, early infantile, 74
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE74 is an autosomal dominant form with onset in the first year of life.
Developmental and epileptic encephalopathy 75
Epileptic encephalopathy, early infantile, 75
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE75 is an autosomal recessive form characterized by onset of severe refractory seizures in the first months of life.
Developmental and epileptic encephalopathy 76
Epileptic encephalopathy, early infantile, 76
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE76 is an autosomal recessive form that may result in death in childhood.
Developmental and epileptic encephalopathy 78
Epileptic encephalopathy, early infantile, 78
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE78 is an autosomal dominant form characterized by onset of refractory seizures in the first days or months of life. Clinical features include severe developmental delay, hypotonia, microcephaly, cortical visual impairment and profound intellectual disability. Some patients manifest a less severe phenotype characterized by pharmacoresponsive epilepsy, autism spectrum disorder and moderate intellectual disability.
Developmental and epileptic encephalopathy 79
Epileptic encephalopathy, early infantile, 79
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE79 is an autosomal dominant form characterized by onset of refractory seizures in the first months of life. Brain imaging may show hypomyelination, cerebral atrophy and thinning of the corpus callosum.
Developmental and epileptic encephalopathy 8
Epileptic encephalopathy, early infantile, 8
A disorder characterized by hyperekplexia and early infantile epileptic encephalopathy. Neurologic features include exaggerated startle response, seizures, impaired psychomotor development, and intellectual disability. Seizures can be provoked by tactile stimulation or extreme emotion.
Developmental and epileptic encephalopathy 80
Epileptic encephalopathy, early infantile, 80
Glycosylphosphatidylinositol biosynthesis defect 20
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE80 is an autosomal recessive form characterized by onset of refractory seizures in the first year of life, severe global developmental delay and/or intellectual disability. Additional variable features include polyneuropathy, hearing loss, visual impairment, dysmorphic or coarse facial features, and distal skeletal abnormalities.
Developmental and epileptic encephalopathy 81
Epileptic encephalopathy, early infantile, 81
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE81 is an autosomal recessive form characterized by onset soon after birth, little developmental progress with no eye contact and no motor or cognitive development. Other features may include facial dysmorphism, such as hypotonic facies and epicanthal folds, as well as sensorineural hearing loss and peripheral neuropathy.
Developmental and epileptic encephalopathy 82
Deficiency of mitochondrial glutamate oxaloacetate transaminase
Epileptic encephalopathy, early infantile, 82
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE82 is an autosomal recessive metabolic encephalopathy characterized by epilepsy from the first year of life, global developmental delay, hypotonia and feeding difficulties apparent soon after birth, and intellectual and motor disabilities. Other features include poor overall growth, progressive microcephaly and biochemical abnormalities, including increased serum lactate and ammonia.
Developmental and epileptic encephalopathy 83
Epileptic encephalopathy, early infantile, 83
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE83 is an autosomal recessive form characterized by onset of frequent, intractable seizures in the first days to months of life. Affected individuals have profound developmental delay with no motor or language skill acquisition, and poor or absent visual tracking. Many patients die in the first years of life.
Developmental and epileptic encephalopathy 84
Epileptic encephalopathy, early infantile, 84
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE84 is an autosomal recessive form characterized by onset of refractory seizures in the first months of life.
Developmental and epileptic encephalopathy 85 with or without midline brain defects
Epileptic encephalopathy, early infantile, 85, with or without midline brain defects
An X-linked form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE85 is characterized by onset of severe refractory seizures in the first year of life, global developmental delay with impaired intellectual development and poor or absent speech, and dysmorphic facial features. Many patients have midline brain defects on brain imaging.
Developmental and epileptic encephalopathy 86
Epileptic encephalopathy, early infantile, 86
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE86 inheritance is autosomal recessive.
Developmental and epileptic encephalopathy 87
Epileptic encephalopathy, early infantile, 87
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE87 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 88
Epileptic encephalopathy, early infantile, 88
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE88 is an autosomal recessive severe form characterized by global developmental delay, epilepsy, and progressive microcephaly.
Developmental and epileptic encephalopathy 89
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE89 is an autosomal recessive severe form characterized by profound global developmental delay with impaired intellectual development, absent speech, inability to sit or walk due to axial hypotonia and spastic quadriparesis, and onset of seizures in the first days or months of life.
Developmental and epileptic encephalopathy 9
Epileptic encephalopathy, early infantile, 9
A condition characterized by seizure with onset in infancy or early childhood, cognitive impairment, and delayed development of variable severity in some patients. Additional features include autistic signs and psychosis. The disorder is sex-limited, with the phenotype being restricted to females.
Developmental and epileptic encephalopathy 90
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE90 is an X-linked form characterized by onset of refractory seizures in the first days or months of life.
Developmental and epileptic encephalopathy 94
Epileptic encephalopathy, childhood-onset
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE94 is an autosomal dominant, severe form characterized by onset of multiple seizure types in the first few years of life.
Developmental and epileptic encephalopathy 96
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE96 is an autosomal dominant form characterized by onset of seizures in the first days or weeks of life. Affected infants also have hypotonia with respiratory insufficiency that may result in premature death.
Developmental and epileptic encephalopathy 97
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE97 is an autosomal dominant form.
Developmental and epileptic encephalopathy 98
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE98 is an autosomal dominant form characterized by onset of seizures in the first decade.
Developmental and epileptic encephalopathy 99
A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE99 is an autosomal dominant form characterized by onset of seizures in early childhood.
Developmental delay and seizures with or without movement abnormalities
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, and early-onset seizures with a myoclonic component. Most patients have delayed motor development and show abnormal movements, including ataxia, dystonia, and tremor.
Developmental delay with dysmorphic facies and dental anomalies
A disorder characterized by mild global developmental delay, impaired intellectual development, walking by 2 to 3 years, and slow language acquisition.The severity of the disorder ranges from moderate cognitive deficits to mild learning difficulties or behavioral abnormalities. Most patients have dysmorphic facial features, abnormal dentition and non-specific visual defects. DEFDA transmission pattern is consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity.
Developmental delay with or without dysmorphic facies and autism
An autosomal dominant neurodevelopmental disorder apparent from infancy or early childhood. Some patients present with intellectual disability and renal, cardiac, genitourinary systems, as well as structural brain abnormalities. In some cases, the phenotype is less severe, has no systemic involvement and is characterized by autism spectrum disorder and/or intellectual disability, sometimes associated with epilepsy. Affected individuals manifest variable dysmorphic features.
Developmental delay with or without intellectual impairment or behavioral abnormalities
An autosomal dominant disorder characterized by a highly variable phenotype of developmental delay, intellectual disability, learning or behavioral problems, muscular hypotonia, and neonatal feeding difficulties.
Developmental delay with short stature, dysmorphic facial features, and sparse hair 1
An autosomal recessive syndrome characterized by intellectual disability, short stature, and craniofacial and ectodermal anomalies including scaphocephaly with or without craniosynostosis, prominent forehead, sparse eyebrows and hair, hypoplastic toenails and, in some cases, dental anomalies.
Developmental delay with short stature, dysmorphic facial features, and sparse hair 2
An autosomal recessive syndrome characterized by developmental delay with variably impaired intellectual development and speech delay, short stature, abnormal head circumference, dysmorphic facial features, and sparse scalp hair. Affected individuals may have other abnormalities, including congenital cardiac defects and distal skeletal anomalies.
Developmental delay with variable intellectual disability and dysmorphic facies
An autosomal dominant disorder characterized by various degrees of developmental delay, mild to moderate intellectual disability, learning difficulties, hypotonia, autistic features, behavior abnormalities, and dysmorphic facial features apparent from infancy or early childhood.
Developmental delay with variable intellectual impairment and behavioral abnormalities
An autosomal dominant disorder characterized by impaired intellectual development with speech difficulties, dysmorphic features, and behavioral abnormalities including autism spectrum disorder, attention deficit and hyperactivity. Additional variable features may include hypotonia, somatic overgrowth, macrocephaly, mild distal skeletal anomalies, sleep disturbances, movement disorders, and gastrointestinal issues, such as constipation.
Developmental delay with variable neurologic and brain abnormalities
An autosomal dominant disorder characterized by onset of motor and speech delay in early childhood. Disease severity and clinical manifestations are highly variable. Most patients have delayed walking and variably impaired intellectual development. Additional features may include seizures, spasticity, and ocular abnormalities. Brain imaging often shows thin corpus callosum and may show white matter atrophy, myelination abnormalities, or enlarged ventricles.
Developmental delay, behavioral abnormalities, and neuropsychiatric disorders
An autosomal dominant disorder characterized by mild global developmental delay, normal or variably impaired intellectual development, and behavioral or neuropsychiatric disorders, including autism spectrum disorder, attention deficit-hyperactivity disorder, and executive functioning deficits. Additional features may include speech delay, dysmorphic features, hypotonia, sleep disturbances, and seizures.
Developmental delay, hypotonia, and impaired language
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, borderline to severe intellectual disability, language difficulties, hypotonia, and gastrointestinal problems. Brain imaging shows variable structural abnormalities affecting the cerebellum, corpus collosum, and white matter.
Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
An autosomal dominant disorder characterized by developmental delay, speech delay, mild to severe intellectual disability, hypotonia, musculoskeletal features, and behavioral abnormalities including autistic features. Skeletal anomalies include joint hypermobility, chronic musculoskeletal pain, scoliosis, and pectus defects. Affected individuals also have non-specific and variable dysmorphic facial features.
Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy
An autosomal dominant disease characterized by developmental delay, intellectual disability, hypotonia, poor growth, short stature, microcephaly, and variable craniofacial dysmorphism. Patients often present weakness, hyporeflexia, and electrophysiologic abnormalities consistent with an axonal sensorimotor peripheral neuropathy. Additional features may include hearing loss, pigmentary retinopathy, and abnormalities on brain imaging, including cerebral or cerebellar atrophy, hypomyelination, and lesions in the basal ganglia or brainstem. Disease severity is highly variable.
Developmental delay, impaired speech, and behavioral abnormalities
An autosomal dominant disorder characterized by developmental delay with speech impairment, mild to severe intellectual disability, and behavioral abnormalities including autistic features. Additional variable manifestations may include dysmorphic facial features, seizures, hypotonia, motor abnormalities, and hearing loss.
Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures
An autosomal dominant disorder characterized by mild to moderately impaired intellectual development, language delay, motor deficits, and behavioral abnormalities including aggression, hyperactivity, and autism spectrum disorder. About half of individuals develop various types of seizures. More variable features include dysmorphic facial features, mild ocular anomalies, and non-specific findings on brain imaging.
Developmental delay, language impairment, and ocular abnormalities
An autosomal dominant disorder characterized by mild motor delay, mildly impaired intellectual development, and significant speech impairment. Most affected individuals have microcephaly and may have mild dysmorphic features. Variable ocular anomalies include strabismus, cataracts, and cortical visual impairment.
Diabetes insipidus, nephrogenic, 1, X-linked
A disorder caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. Characterized by excessive water drinking (polydipsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia.
Diabetes insipidus, nephrogenic, 2, autosomal
A disorder caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. Characterized by excessive water drinking (polydipsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. Inheritance can be autosomal dominant or recessive.
A disease characterized by persistent thirst, polydipsia and polyuria. Affected individuals are apparently normal at birth, but characteristically develop symptoms of vasopressin deficiency during childhood.
An atypical form of diabetes mellitus characterized by an acute initial presentation with severe hyperglycemia and ketosis, as seen in classic type 1 diabetes, but after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies show a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic beta-cell autoimmunity is a rare finding.
Diabetes mellitus, neonatal, with congenital hypothyroidism
A syndrome of neonatal diabetes syndrome associated with congenital hypothyroidism, congenital glaucoma, hepatic fibrosis and polycystic kidneys.
Diabetes mellitus, permanent neonatal, 1
Developmental delay epilepsy and neonatal diabetes
Diabetes mellitus permanent neonatal with neurologic features
An autosomal recessive form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive.
Diabetes mellitus, permanent neonatal, 2
Developmental delay, epilepsy, and neonatal diabetes 1
Diabetes, permanent neonatal 2, with or without neurologic features
A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM2 patients may also have developmental delay, muscle weakness, epilepsy and dysmorphic features. PNDM2 transmission pattern is consistent with autosomal dominant inheritance.
Diabetes mellitus, permanent neonatal, 3
Developmental delay, epilepsy, and neonatal diabetes 2
Diabetes, permanent neonatal 3, with or without neurologic features
A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM3 patients may also have developmental delay, muscle weakness, and epilepsy. PNDM3 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance.
Diabetes mellitus, permanent neonatal, 4
A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. PNDM4 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance.
Diabetes mellitus, transient neonatal, 1
An autosomal dominant form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first month of life. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes.
Congenital hypoplastic anemia of Blackfan and Diamond
A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of developing leukemia. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies.
A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies.
Diamond-Blackfan anemia 14, with mandibulofacial dysostosis
Diamond-Blackfan anemia 15, with mandibulofacial dysostosis
Diamond-Blackfan anemia with microtia and cleft palate
A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. DBA18 inheritance is autosomal dominant.
A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. DBA19 inheritance is autosomal dominant.
A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. DBA20 inheritance is autosomal dominant.
An autosomal recessive form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. DBA21 patients manifest bone marrow failure, short stature, facial and acromelic dysmorphic features, and intellectual disability.
An autosomal recessive hematologic disease characterized by severe red cell hypoplastic anemia, selective absence of red cell precursors and progenitors seen on bone marrow biopsy, and increased serum erythropoietin.
Defect in vertebral ossification with nephrogenic rests
A rare, recessively inherited, perinatal lethal skeletal disorder. The primary skeletal characteristics of the phenotype include a small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, a depressed nasal bridge with a short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases.
A form of congenital diaphragmatic hernia, a posterolateral defect of the diaphragm, generally located on the left side, that permits the herniation of abdominal viscera into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects.
Diaphragmatic hernia 4, with cardiovascular defects
An autosomal recessive form of congenital diaphragmatic hernia, a posterolateral defect of the diaphragm, generally located on the left side, that permits the herniation of abdominal viscera into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects.
Diaphyseal medullary stenosis with malignant fibrous histiocytoma
Bone dysplasia with malignant fibrous histiocytoma
Bone dysplasia with medullary fibrosarcoma
Limb-girdle myopathy with bone fragility
An autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. Some patients show a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma.
Diarrhea 1, secretory chloride, congenital
Congenital chloride diarrhea Finnish type
Diarrhea 1 secretory chloride congenital
A disease characterized by voluminous watery stools containing an excess of chloride. The children with this disease are often premature.
Diarrhea 10, protein-losing enteropathy type
An autosomal recessive, congenital diarrheal disorder characterized by intractable secretory diarrhea with massive protein loss due to leaky fenestrated capillaries, severe hypoalbuminemia, hypogammaglobulinemia, hypertriglyceridemia, and electrolyte abnormalities. Disease severity is variable and death in infancy may occur in severe cases. Some patients show facial dysmorphic features, and cardiac and renal abnormalities.
Intractable diarrhea of infancy syndrome
A disease characterized by severe, life-threatening watery diarrhea associated with generalized malabsorption and a paucity of enteroendocrine cells. DIAR11 is characterized by onset of intractable diarrhea within the first few weeks of life.
An autosomal recessive congenital enteropathy characterized by intractable secretory diarrhea, resulting in severe dehydration and metabolic acidosis. DIAR12 can be diagnosed based on variable loss of brush-border microvilli, microvillus inclusions, and accumulation of subapical vesicles in villus enterocytes.
Diarrhea 2, with microvillus atrophy, with or without cholestasis
Congenital familial protracted diarrhea with enterocyte brush-border abnormalities
A disease characterized by onset of intractable life-threatening watery diarrhea during infancy. Two forms are recognized: early-onset microvillus inclusion disease with diarrhea beginning in the neonatal period, and late-onset, with first symptoms appearing after 3 or 4 months of life.
Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies
Diarrhea 3, secretory sodium, congenital, syndromic
A disease characterized by life-threatening secretory diarrhea, severe metabolic acidosis and hyponatremia. Hyponatremia is secondary to extraordinarily high fecal sodium loss, with low or normal excretion of urinary sodium, in the absence of infectious, autoimmune and endocrine causes.
A disease characterized by severe, life-threatening watery diarrhea associated with generalized malabsorption and a paucity of enteroendocrine cells.
Diarrhea 5, with tufting enteropathy, congenital
An intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum.
A relatively mild, early-onset chronic diarrhea that may be associated with increased susceptibility to inflammatory bowel disease, small bowel obstruction, and esophagitis.
Diarrhea 7, protein-losing enteropathy type
A life-threatening disease characterized by severe, intractable, watery diarrhea.
Diarrhea 8, secretory sodium, congenital
A disease characterized by watery secretory diarrhea with prenatal onset, prominent abdominal distension after birth due to dilated fluid-filled loops of intestine, elevated fecal sodium concentrations and low urinary sodium concentrations.
An autosomal recessive form of chronic diarrhea characterized by neonatal-onset of osmotic diarrhea that is not substrate specific, abnormal crypt and villus architecture, and significant fat malabsorption evidenced by high levels of fecal fat.
An autosomal recessive disease characterized by osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities.
An autosomal recessive disorder characterized by abnormal excretion of urinary glutamate and aspartate, resulting from the incomplete reabsorption of anionic amino acids from the glomerular filtrate in the kidney. It can be associated with intellectual disability.
Diencephalic-mesencephalic junction dysplasia syndrome 1
Microcephaly, seizures, spasticity, and brain calcifications
An autosomal recessive syndrome characterized by severe global developmental delay with profound intellectual disability, spasticity or dystonia, and congenital microcephaly. Brain imaging shows hypothalamic midbrain dysplasia, diencephalic-mesencephalic dysplasia, and intracerebral calcifications.
Diencephalic-mesencephalic junction dysplasia syndrome 2
Spastic tetraparesis, dystonia, developmental delay, and structural abnormalities of the basal ganglia
An autosomal recessive neurodevelopmental disorder with onset at birth, characterized by severe global developmental delay, hypotonia, spastic tetraparesis, generalized dystonia and severe intellectual impairment. Brain imaging shows a unique brain malformation characterized by agenesis of putamina and globi pallidi, dysgenesis of the caudate nuclei, olfactory bulbs hypoplasia, and anomaly of the diencephalic-mesencephalic junction with abnormal corticospinal tract course.
Intellectual developmental disorder with distinctive facial dysmorphism
An autosomal dominant disorder characterized by varying degrees of intellectual disability, developmental delay, short stature, and characteristic facial features such as a wide mouth, a pointed chin, long ears and a low columella.
Diffuse gastric and lobular breast cancer syndrome
Gastric cancer familial diffuse and cleft lip with or without cleft palate
A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. In addition to gastric cancer, most female mutation carriers develop lobular carcinoma of the breast.
Third and fourth pharyngeal pouch syndrome
A congenital syndrome characterized by a wide spectrum of characteristics including parathyroid hypoplasia resulting in hypocalcemia, thymic hypoplasia resulting in T-cell immunodeficiency, defects in the outflow tract of the heart, and craniofacial anomalies. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype.
Digital arthropathy-brachydactyly, familial
A disorder characterized by irregularities in the proximal articular surfaces of the distal interphalangeal joints of the hand. Individuals appear normal at birth, with no clinical or radiographic evidence of a developmental skeletal dysplasia. The earliest changes appear during the first decade of life. By adulthood, all interphalangeal, metacarpophalangeal, and metatarsophalangeal joints are affected by a deforming, painful osteoarthritis. The remainder of the skeleton is clinically and radiographically unaffected.
A rare genodermatosis characterized by enlargement of the nail plate and terminal segments of the fingers and toes, resulting from proliferation of the connective tissues between the nail matrix and the distal phalanx. It is usually symmetrical and bilateral (in some cases unilateral). In nail clubbing usually the distal end of the nail matrix is relatively high compared to the proximal end, while the nail plate is complete but its dimensions and diameter more or less vary in comparison to normal. There may be different fingers and toes involved to varying degrees. Some fingers or toes are spared, but the thumbs are almost always involved.
Dihydrolipoamide dehydrogenase deficiency
Lactic acidosis due to lipoamide dehydrogenase deficiency
An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism.
Dihydropyrimidinuria due to DPYS deficiency
An autosomal recessive disorder of pyrimidine metabolism characterized by dihydropyrimidinuria. It is associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Most patients are, however, asymptomatic.
Dihydropyrimidine dehydrogenase deficiency
A metabolic disorder with large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and intellectual disability. It is characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil.
Disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency
Adrenal hyperplasia congenital due to cytochrome P450 oxidoreductase deficiency
Congenital adrenal hyperplasia due to apparent combined P450C17 and P450C21 deficiency
Disordered steroidogenesis due to POR deficiency
A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.
Distal myopathy with anterior tibial onset
Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. Inheritance is autosomal recessive.
Distal spinal muscular atrophy, autosomal recessive, 2
Hereditary motor neuropathy, Jerash type
Neuronopathy, distal hereditary motor, Jerash type
Neuropathy, distal hereditary motor, Jerash type
An autosomal recessive neuromuscular disorder characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade. There is no sensory involvement.
Distal spinal muscular atrophy, autosomal recessive, 4
A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. DSMA4 is characterized by childhood onset, generalized muscle weakness and atrophy with denervation and normal sensation. Bulbar symptoms and pyramidal signs are absent.
Distal spinal muscular atrophy, autosomal recessive, 5
An autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired.
Distal spinal muscular atrophy, autosomal recessive, 6
A form of distal spinal muscular atrophy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. DSMA6 is an autosomal recessive form characterized by onset of distal muscle weakness in early infancy. Affected individuals often present at birth with distal joint contractures or foot deformities and show delayed motor development, often with inability to walk or frequent falls. Patients often show respiratory distress or diaphragmatic palsy. Electrophysiologic studies are consistent with a peripheral motor neuropathy without sensory involvement.
Distal spinal muscular atrophy, X-linked, 3
Spinal muscular atrophy distal X-linked recessive
A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.
Disorder characterized by fish odor, muscle fatigue with increased serum creatine kinase. Biochemically it is characterized by an increase of N,N-dimethylglycine (DMG) in serum and urine.
Dominant nonimmune chronic idiopathic neutropenia of adults
Relatively mild form of neutropenia diagnosed in adults, but predisposing to leukemia in a subset of patients.
Optic atrophy with or without deafness ophthalmoplegia myopathy ataxia and neuropathy
A neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes.
Dominantly inherited venous malformations
An error of vascular morphogenesis characterized by dilated, serpiginous channels.
Rare autosomal recessive disorder characterized by major malformations including agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. The FOAR syndrome was first described as comprising facial anomalies, ocular anomalies, sensorineural hearing loss, and proteinuria. DBS and FOAR were first described as distinct disorders but the classic distinguishing features between the 2 disorders were presence of proteinuria and absence of diaphragmatic hernia and corpus callosum anomalies in FOAR. Early reports noted that the 2 disorders shared many phenotypic features and may be identical. Although there is variability in the expression of some features (e.g., agenesis of the corpus callosum and proteinuria), DBS and FOAR are now considered to represent the same entity.
An autosomal dominant genodermatosis. Affected individuals develop a postpubertal reticulate hyperpigmentation that is progressive and disfiguring, and small hyperkeratotic dark brown papules that affect mainly the flexures and great skin folds. Patients usually show no abnormalities of the hair or nails.
A form of Dowling-Degos disease, a genodermatosis manifesting with postpubertal reticulate hyperpigmentation that is progressive and disfiguring, and small hyperkeratotic dark brown papules that affect mainly the flexures and great skin folds. Patients usually show no abnormalities of the hair or nails. DDD4 is characterized by prominent involvement of non-flexural skin areas.
Autosomal dominant disease characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium.
Developmental and epileptic encephalopathy 6A
Epileptic encephalopathy, early infantile, 6
A severe form of epileptic encephalopathy characterized by generalized tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex partial seizures. Psychomotor development delay is observed around the second year of life. Some patients manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core DRVT. DRVT is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile seizures-plus.
A form of Duane retraction syndrome, a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction or both, narrowing of the palpebral fissure, and retraction of the globe on attempted adduction. Undiagnosed in children, it can lead to amblyopia, a permanent uncorrectable loss of vision.
Duane retraction syndrome 3 with or without deafness
A form of Duane retraction syndrome, a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction or both, narrowing of the palpebral fissure, and retraction of the globe on attempted adduction. Undiagnosed in children, it can lead to amblyopia, a permanent uncorrectable loss of vision. Some DURS3 patients manifest sensorineural hearing loss.
Disorder characterized by the association of forearm malformations with Duane retraction syndrome.
Autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function.
Most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment.
Pulmonary arterial hypertension leukopenia and atrial septal defect
A disease characterized by pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, intermittent neutropenia, lymphopenia, monocytosis and anemia.
Dworschak-Punetha neurodevelopmental syndrome
An autosomal recessive disorder characterized by global developmental delay, mildly impaired intellectual development, speech delay, and behavioral abnormalities including autism spectrum disorder and hyperactivity. Additional variable additional features include optic disk hypoplasia, ptosis, hypo- or hyperpigmented skin lesions, non-specific facial dysmorphism, and abnormalities of the ventricles or corpus callosum seen on brain imaging.
A rare autosomal recessive disorder belonging to the group of spondyloepimetaphyseal dysplasias. DMC is characterized by progressive short stature with short trunk dwarfism, microcephaly, protruding sternum, and psychomotor retardation. Radiological features include a platyspondyly with double vertebral humps, an epiphyso-metaphyseal dysplasia and lacy pelvis iliac crests.
Symmetric dyschromatosis of the extremities
An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and the dorsal parts of the hands and feet, that appear in infancy or early childhood.
Dyschromatosis universalis hereditaria 1
A form of dyschromatosis universalis, an autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications.
Dyschromatosis universalis hereditaria 3
An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications.
A disorder characterized by qualitative abnormalities (dysfibrinogenemia) of the circulating fibrinogen. Affected individuals are frequently asymptomatic, but some patients have bleeding diathesis, thromboembolic complications, or both. In some cases, dysfibrinogenemia is associated with low circulating fibrinogen levels (hypodysfibrinogenemia).
Dyskeratosis congenita, autosomal dominant, 2
A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Dyskeratosis congenita, autosomal dominant, 3
Dyskeratosis congenita, autosomal dominant, 4
Dyskeratosis congenita, autosomal dominant, 5
Exudative retinopathy with bone marrow failure
A disease characterized by bone marrow hypoplasia, nail dystrophy, fine sparse hair, fine reticulate skin pigmentation, oral leukoplakia, bilateral exudative retinopathy, cerebellar hypoplasia, and growth retardation.
Dyskeratosis congenita, autosomal dominant, 6
A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Dyskeratosis congenita, autosomal recessive, 1
Dyskeratosis congenita, autosomal recessive, 2
Dyskeratosis congenita, autosomal recessive, 3
Dyskeratosis congenita, autosomal recessive, 4
A severe form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Dyskeratosis congenita, autosomal recessive, 5
A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCB5 is characterized by onset of bone marrow failure and immunodeficiency in early childhood. Most patients also have growth and developmental delay and cerebellar hypoplasia, consistent with a clinical diagnosis of Hoyeraal-Hreidarsson syndrome.
Dyskeratosis congenita, autosomal recessive, 6
Dyskeratosis congenita, autosomal recessive, 7
Dyskeratosis congenita, autosomal recessive, 8
A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. Additional DKCB8 features include microcephaly, intrauterine growth retardation, and developmental anomalies in some patients. DKCB8 patients exhibit normal global telemore length, although there is evidence of telomere instability.
A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCD transmission pattern is consistent with digenic inheritance.
A rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Dyskinesia with orofacial involvement, autosomal recessive
An autosomal recessive disorder characterized by abnormal involuntary movements mainly affecting the limbs and causing walking difficulties, oro-facial dyskinesia, and speech delay. Some patients develop neuropsychiatric features. Cardiomyopathy has rarely been described and may be a manifestation of the disorder.
Dyskinesia, familial, with facial myokymia
A disorder characterized by predominantly perioral and periorbital myokymia, and face, neck and upper limb dystonic/choreic movements. Initially paroxysmal and worsened by stress, the dyskinetic episodes become nearly constant by the end of the third decade of life, but in some individuals, they may diminish in frequency and severity at older ages.
Dyskinesia, limb and orofacial, infantile-onset
An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable.
A relatively common, complex cognitive disorder characterized by an impairment of reading performance despite adequate motivational, educational and intellectual opportunities. It is a multifactorial trait, with evidence for familial clustering and heritability.
An autosomal recessive, severe skeletal disease characterized by features of dysostosis multiplex, severe short stature, coarse facies with broad nose and prominent lips, protruding abdomens, and progressive skeletal changes causing gradual mobility loss. Death in childhood or early adulthood may occur.
Dyssegmental dysplasia Silverman-Handmaker type
The dyssegmental dysplasias are rare, autosomal recessive skeletal dysplasias with anisospondyly and micromelia. There are two recognized types: the severe, lethal DDSH and the milder Rolland-Desbuquois form. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocoele. The endochondral growth plate is short, the calcospherites (which are spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage.
A primary torsion dystonia, and the most common and severe form. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 1 is characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body, in the absence of other neurological symptoms. Typically, symptoms develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. 'Torsion' refers to the twisting nature of body movements observed in DYT1, often affecting the trunk. Distribution and severity of symptoms vary widely between affected individuals, ranging from mild focal dystonia to severe generalized dystonia, even within families.
A myoclonic dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT11 is characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Inheritance is autosomal dominant. The age of onset, pattern of body involvement, presence of myoclonus and response to alcohol are all variable.
An autosomal dominant dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT12 patients develop dystonia and parkinsonism between 15 and 45 years of age. The disease is characterized by an unusually rapid evolution of signs and symptoms. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability.
An early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.
Dystonia 2, torsion, autosomal recessive
A form of torsion dystonia, a disease defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. 'Torsion' refers to the twisting nature of body movements, often affecting the trunk. DYT2 is a slowly progressive form that first affects distal limbs and later involves the neck, orofacial, and craniocervical regions.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT23 is an autosomal dominant dystonia affecting the face, neck, limbs. Some DYT23 patients manifest generalized myoclonus in addition to progressive action-induced multifocal dystonia.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT24 is an autosomal dominant focal dystonia affecting the neck, laryngeal muscles, and muscles of the upper limbs.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT25 is an autosomal dominant neurologic disorder characterized by adult onset of focal dystonia, usually involving the neck. The dystonia most often progresses to involve other regions, particularly the face and laryngeal muscles, and less commonly the trunk and limbs.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT26 is an autosomal dominant, progressive disorder characterized by a combination of non-epileptic myoclonic jerks and dystonia. Affected individuals manifest myoclonic jerks in the upper limbs during the first or second decade of life, and later develop dystonia with predominant involvement of the craniocervical regions and sometimes the trunk and/or lower limbs.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT27 is an autosomal recessive form characterized by segmental isolated dystonia involving the face, neck, bulbar muscles, and upper limbs.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT28 is an autosomal dominant, progressive form characterized by onset in the first decade of life and variable severity. Dystonia begins focally in the lower limbs, resulting in gait difficulties, with later progression to other body regions, including the upper limbs, neck, and orofacial region.
Torsion dystonia-parkinsonism Filipino type
An X-linked dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT3 is characterized by severe progressive torsion dystonia followed by parkinsonism. It has a well-defined pathology of extensive neuronal loss and mosaic gliosis in the striatum (caudate nucleus and putamen) which appears to resemble that in Huntington disease.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT30 is characterized by early onset and predominantly cervical, bulbar, orofacial, and upper limb involvement. Some patients have a more complex phenotype with neurocognitive impairment, including mild intellectual disability or psychiatric manifestations. Loss of ambulation is observed in some cases. DYT30 inheritance is autosomal dominant with incomplete penetrance.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT31 is an autosomal recessive, progressive form with onset from childhood to young adulthood. Involuntary muscle twisting movements and postural abnormalities affect the upper and lower limbs, neck, face, and trunk. Some patients may have orofacial dyskinesia resulting in articulation and swallowing difficulties.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT32 is an autosomal recessive, slowly progressive form with onset in adulthood and generalized involvement of the limbs, trunk, neck, and larynx, resulting in dysarthria and dysphagia. Brain imaging may show abnormalities in the basal ganglia.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT33 is a slowly progressive form characterized by onset of focal or generalized dystonia in the first decades of life. Disease manifestations are variable. Some patients show ambulation difficulties, dysarthria, or dysphagia. Some affected individuals may manifest motor delay, lower limb spasticity, and mild developmental delay with intellectual disability. DYT33 penetrance is incomplete. Inheritance can be autosomal dominant or recessive.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT34 is an autosomal dominant form characterized by childhood-onset dystonia predominantly affecting hands and neck, with a fast tremor with superimposed myoclonus and, in some individuals, subtle cerebellar signs.
A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT35 is an autosomal recessive form characterized by the onset of a dystonic movement disorder in the first year of life.
A form of torsion dystonia, a disease defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. 'Torsion' refers to the twisting nature of body movements, often affecting the trunk. DYT4 is characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait.
A primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterized by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions.
A paroxysmal non-kinesigenic dystonia/dyskinesia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 8 is characterized by attacks of involuntary movements brought on by stress, alcohol, fatigue or caffeine. The attacks generally last between a few seconds and four hours or longer. The attacks may begin in one limb and spread throughout the body, including the face.
Kinesigenic choreoathetosis with episodic ataxia and spasticity
Paroxysmal choreoathetosis with episodic ataxia
An autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most patients show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia.
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
An autosomal recessive neurologic disorder characterized by childhood-onset dystonia, basal ganglia degeneration and optic atrophy with decreased visual acuity. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTOABG severity is variable, and some patients lose independent ambulation.
Autosomal dominant dopa-responsive dystonia
Dystonia-parkinsonism with diurnal fluctuation
Progressive dystonia with diurnal fluctuation
A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise.
Dystonia, DOPA-responsive, due to sepiapterin reductase deficiency
Motor and cognitive disorder due to sepiapterin reductase deficiency
A form of DOPA-responsive dystonia. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.
Dystonia, early-onset, and/or spastic paraplegia
An autosomal dominant, highly penetrant movement disorder characterized by spastic paraplegia and/or dystonia to varying degrees in affected individuals. Cognition is not affected. There is high intra- and interfamilial variability in phenotype and age of onset. Some patients have onset of progressive focal or generalized dystonia in the first decade, whereas others develop progressive spastic paraplegia as adults. Some affected individuals have manifestations of both disorders.
Developmental malformations-deafness-dystonia
A form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. Patients with juvenile-onset dystonia manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.
A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias.
A multisystem disease characterized by the association of proximal muscle weakness with myotonia, cardiac manifestations and cataract. Additional features can include hyperhidrosis, testicular atrophy, insulin resistance and diabetes and central nervous system anomalies in rare cases.
Early-onset hypertension with severe exacerbation in pregnancy
Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.
Ectodermal dysplasia 1, hypohidrotic, X-linked
Ectodermal dysplasia 1 hypohidrotic/hair/tooth type X-linked
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. It is the most common form of over 150 clinically distinct ectodermal dysplasias.
Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant
Ectodermal dysplasia hypohidrotic autosomal dominant
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands.
Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive
Ectodermal dysplasia hypohidrotic autosomal recessive
A disorder due to abnormal development of two or more ectodermal structures, and characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Ectodermal dysplasia 11A, hypohidrotic/hair/nail type, autosomal dominant
Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive
Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type
A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD12 is an autosomal dominant, hypohidrotic form characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth, and the inability to sweat due to defective development of sweat glands.
Ectodermal dysplasia 13, hair/tooth type
A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD13 is an autosomal recessive form characterized by severe oligodontia accompanied by anomalies of hair and skin.
Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis
A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD14 is an autosomal recessive form characterized by scalp hypotrichosis, hypodontia, and mild facial dysmorphism. Some patients have decreased sweating.
Ectodermal dysplasia 15, hypohidrotic/hair type
A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD15 is an autosomal recessive form characterized by hypotrichosis and absence of sweating except with extreme exercise. Skin is dry from birth and eczematous lesions may develop in adulthood. Other features include blepharitis and photophobia.
Ectodermal dysplasia hidrotic autosomal dominant
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD2 is an autosomal dominant condition characterized by atrichosis, nail hypoplasia and deformities, hyperpigmentation of the skin, normal teeth, normal sweat and sebaceous gland function. Palmoplantar hyperkeratosis is a frequent feature. Hearing impairment has been detected in few cases.
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD3 is characterized by abnormalities largely limited largely to teeth (some of which are missing) and nails (which are poorly formed early in life, especially toenails). This condition is distinguished from anhidrotic ectodermal dysplasia by autosomal dominant inheritance and little involvement of hair and sweat glands. The teeth are not as severely affected.
Ectodermal dysplasia pure hair-nail type
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD4 is characterized by complete alopecia, hypotricosis and nail dystrophy in all digits. There is no evidence of any other abnormality. Inheritance can be autosomal dominant or recessive.
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. Ectodermal dysplasia of the hair/nail type is characterized by hypotrichosis and nail dystrophy without non-ectodermal or other ectodermal manifestations.
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD9 is characterized by hypotrichosis and nail dystrophy without non-ectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia).
Ectodermal dysplasia and immunodeficiency 1
Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis and lymphedema
Ectodermal dysplasia, anhidrotic, with immunodeficiency X-linked
Ectodermal dysplasia anhidrotic with immune deficiency
Ectodermal dysplasia hypohidrotic with immunodeficiency
Hyper-IgM immunodeficiency X-linked with ectodermal dysplasia hypohidrotic
A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDAID1 is an X-linked recessive disorder characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, and may be fatal in childhood.
Ectodermal dysplasia and immunodeficiency 2
Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency autosomal dominant
A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. This form of ectodermal dysplasia is associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection. EDAID2 inheritance is autosomal dominant.
Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies
A neuroectodermal syndrome characterized by linear hypopigmentation, alopecia, apparently asymptomatic leukoencephalopathy, and facial, ocular, dental and acral anomalies. Patients show no intellectual or neurologic impairment.
Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal recessive condition characterized by features of ectodermal dysplasia such as sparse eyebrows and scalp hair, and selective tooth agenesis associated with macular dystrophy and ectrodactyly.
Ectodermal dysplasia, Margarita Island type
Cleft lip/palate-ectodermal dysplasia syndrome
Syndactyly-ectodermal dysplasia-cleft lip/palate
An autosomal recessive form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is a syndrome characterized by the association of cleft lip/palate, ectodermal dysplasia (sparse short and dry scalp hair, sparse eyebrows and eyelashes), and partial syndactyly of the fingers and/or toes. Two thirds of the patients do not manifest oral cleft but present with abnormal teeth and nails.
Ectodermal dysplasia-skin fragility syndrome
Ectodermal dysplasia/skin fragility syndrome
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by features of both cutaneous fragility and congenital ectodermal dysplasia affecting skin, hair and nails. There is no evidence of significant abnormalities in other epithelia or tissues. Desmosomes in the skin are small and poorly formed with widening of keratinocyte intercellular spaces and perturbed desmosome/keratin intermediate filament interactions.
Ectodermal dysplasia-syndactyly syndrome 1
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDSS1 is characterized by the association of hair and teeth abnormalities with cutaneous syndactyly of the hands and/or feet. Hair morphologic abnormalities include twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consist of abnormally widely spaced teeth, with peg-shaped and conical crowns. Patients have normal sweating.
Ectodermal dysplasia/short stature syndrome
An autosomal recessive ectodermal dysplasia syndrome characterized by nail dystrophy and/or loss, oral mucosa and/or tongue pigmentation, abnormal dentition, keratoderma affecting the margins of the palms and soles, focal hyperkeratosis of the dorsal aspects of the hands and feet, and short stature.
Ectopia lentis 1, isolated, autosomal dominant
An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation.
Ectopia lentis 2, isolated, autosomal recessive
An ocular abnormality characterized by displacement of the lenses and the pupils, associated with other ocular anomalies, but without systemic manifestations. The condition is usually bilateral, with the lenses and pupils displaced in opposite directions. Additional signs include enlarged corneal diameter, increased corneal astigmatism, increased anterior chamber depth, thinning and flattening of the iris with loss of crypts, angle malformation caused by enlarged iris processes, persistent pupillary membrane, loss of zonular fibers, tilted disk, and increased axial length. Secondary manifestations include refractive errors, glaucoma, early cataract development, and retinal detachment. Membrane formation on the posterior aspect of the iris has been observed both in histologic sections and on ultrasound biomicroscopy.
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.
Ehlers-Danlos syndrome, arthrochalasia type, 1
Ehlers-Danlos syndrome arthrochalasic type
Ehlers-Danlos syndrome type VIIA, autosomal dominant
A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSARTH1 is an autosomal dominant form characterized by frequent congenital hip dislocation and extreme joint laxity with recurrent joint subluxations and minimal skin involvement.
Ehlers-Danlos syndrome, arthrochalasia type, 2
Ehlers-Danlos syndrome, type VIIB, autosomal dominant
A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSARTH2 is an autosomal dominant condition characterized by frequent congenital hip dislocation and extreme joint laxity with recurrent joint subluxations and minimal skin involvement.
Ehlers-Danlos syndrome, cardiac valvular type
Ehlers-Danlos syndrome, autosomal recessive, cardiac valvular form
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSCV is an autosomal recessive disease characterized by mitral valve prolapse and insufficiency, mitral regurgitation, and aortic insufficiency, in addition to joint laxity, skin hyperextensibility and friability, and abnormal scar formation.
Ehlers-Danlos syndrome, severe classic type
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. The main features of classic Ehlers-Danlos syndrome are joint hypermobility and dislocation, and fragile, bruisable skin. EDSCL1 inheritance is autosomal dominant.
Ehlers-Danlos syndrome mild classic type
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. The main features of classic Ehlers-Danlos syndrome are joint hypermobility and dislocation, and fragile, bruisable skin. EDSCL2 inheritance is autosomal dominant.
Ehlers-Danlos syndrome, autosomal recessive, due to tenascin X deficiency
Ehlers-Danlos syndrome due to tenascin X deficiency
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSCLL patients lack atrophic scars, a major diagnostic criteria for classic Ehlers-Danlos syndrome. Delayed wound healing is only present in a subset of patients. EDSCLL inheritance is autosomal recessive.
A variant form of Ehlers-Danlos syndrome, a connective tissue disorder. EDSCLL2 patients show severe joint and skin laxity, osteoporosis affecting the hips and spine, osteoarthritis, soft redundant skin that can be acrogeria-like, delayed wound healing with abnormal atrophic scarring, and shoulder, hip, knee, and ankle dislocations. Additional variable features include gastrointestinal and genitourinary manifestations (bowel rupture, gut dysmotility, cryptorchidism, and hernias), vascular complications (mitral valve prolapse and aortic root dilation), and skeletal anomalies. EDSCLL2 inheritance is autosomal recessive.
Ehlers-Danlos syndrome, dermatosparaxis type
Ehlers-Danlos syndrome, type VII, autosomal recessive
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSDERMS is an autosomal recessive form characterized by extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age.
Ehlers-danlos syndrome, hypermobility type
A connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. It is a form of Ehlers-Danlos syndrome characterized by marked joint hyperextensibility without skeletal deformity.
Ehlers-Danlos syndrome, kyphoscoliotic type, 1
Ehlers-Danlos syndrome kyphoscoliotic type
Ehlers-Danlos syndrome oculoscoliotic type
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSKSCL1 is an autosomal recessive form characterized by severe muscle hypotonia at birth, generalized joint laxity, scoliosis at birth, and scleral fragility and rupture of the ocular globe.
Ehlers-Danlos syndrome, kyphoscoliotic type, 2
Ehlers-Danlos syndrome, with progressive kyphoscoliosis, myopathy, and hearing loss
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSKSCL2 is an autosomal recessive form characterized by severe generalized hypotonia at birth, myopathy, early-onset progressive kyphoscoliosis, joint hypermobility without contractures, hyperelastic skin with follicular hyperkeratosis, easy bruising, and occasional abnormal scarring, sensorineural hearing impairment, and normal pyridinoline excretion in urine.
Ehlers-Danlos syndrome, musculocontractural type 1
Adducted thumbs-arthrogryposis Dundar type
Arthrogryposis distal with peculiar facies and hydronephrosis
A form of Ehlers-Danlos syndrome characterized by distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruisability and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement.
Ehlers-Danlos syndrome, musculocontractural type 2
A form of Ehlers-Danlos syndrome characterized by progressive multisystem manifestations, including joint dislocations and deformities, skin hyperextensibility, skin bruisability and fragility with recurrent large subcutaneous hematomas, cardiac valvular, respiratory, gastrointestinal, and ophthalmologic complications. Motor developmental delay is associated with muscle hypoplasia, muscle weakness, and an abnormal muscle fiber pattern in histology in adulthood.
Ehlers-Danlos syndrome, periodontal type, 1
Ehlers-Danlos syndrome, periodontitis type
Ehlers-Danlos syndrome, periodontosis type
A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD1 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD1 inheritance is autosomal dominant.
Ehlers-Danlos syndrome, periodontal type, 2
A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD2 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD2 transmission pattern is consistent with autosomal dominant inheritance.
Ehlers-Danlos syndrome, spondylodysplastic type, 1
Defective biosynthesis of proteodermatan sulfate
Ehlers-Danlos syndrome, progeroid type, 1
Ehlers-Danlos syndrome with short stature and limb anomalies
Xylosylprotein 4-beta-galactosyltransferase deficiency
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSSPD1 is an autosomal recessive form characterized by short stature, developmental anomalies of the forearm bones and elbow, and bowing of extremities, in addition to the classic features of Ehlers-Danlos syndrome.
Ehlers-Danlos syndrome, spondylodysplastic type, 2
Ehlers-Danlos syndrome, progeroid type, 2
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSSPD2 is an autosomal recessive form characterized by an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin.
Ehlers-Danlos syndrome, spondylodysplastic type, 3
Ehlers-Danlos syndrome-like spondylocheirodysplasia
A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSSPD3 is an autosomal recessive form characterized by a generalized skeletal dysplasia involving mainly the spine and striking clinical abnormalities of the hands, in addition to classic features of Ehlers-Danlos syndrome. Clinical features include postnatal growth retardation, moderate short stature, protuberant eyes with bluish sclerae, hands with finely wrinkled palms, atrophy of the thenar muscles, and tapering fingers. Radiologic features include mild to moderate platyspondyly, mild to moderate osteopenia of the spine, small ileum, flat proximal femoral epiphyses, short, wide femoral necks, and broad metaphyses (elbows, knees, wrists, and interphalangeal joints).
Ehlers-Danlos syndrome, type IV, autosomal dominant
A severe form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSVASC is an autosomal dominant disease characterized by joint and dermal manifestations as in other forms of the syndrome, and by proneness to spontaneous rupture of bowel and large arteries. The vascular complications may affect all anatomical areas.
An autosomal recessive skeletal dysplasia characterized by severely retarded ossification, principally of the epiphyses, pelvis, hands and feet, as well as by abnormal modeling of the bones in hands and feet, abnormal persistence of cartilage in the pelvis and mild growth retardation.
Autosomal recessive condition characterized by skin hypopigmentation, the presence of large clumps of pigment in hair shafts, silvery-gray hair, accumulation of melanosomes in melanocytes and primary neurological abnormalities. Elejalde syndrome may be the same entity as Griscelli syndrome type I.
A Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.
A Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.
A Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous hematologic disorder characterized by variable hemolytic anemia and elliptical or oval red cell shape. Inheritance can be autosomal dominant or autosomal recessive.
An autosomal recessive condition characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital heart defects, most commonly an atrioventricular septal defect, are observed in 60% of affected individuals.
Hypospadias, hypertelorism, upper lid coloboma, and mixed-type hearing loss
An autosomal recessive syndrome characterized by moderate intellectual disability, hypospadias and characteristic craniofacial morphology, which includes brachycephaly, facial asymmetry, exotropia, hypertelorism, telechantus, broad nose, concave nasal ridge, underdeveloped mid-face, prognathism, and radicular dentin dysplasia.
Emery-Dreifuss muscular dystrophy 1, X-linked
Muscular dystrophy tardive Dreifuss-Emery type with contractures
X-linked Emery-Dreifuss muscular dystrophy
A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.
Emery-Dreifuss muscular dystrophy 2, autosomal dominant
Autosomal dominant Emery-Dreifuss muscular dystrophy
Cardiomyopathy, dilated, with quadriceps myopathy
Hauptmann-Thannhauser muscular dystrophy
Muscular dystrophy, limb-girdle, type 1B
Muscular dystrophy with early contractures and cardiomyopathy autosomal dominant
Scapuloilioperoneal atrophy with cardiopathy
Emery-Dreifuss muscular dystrophy 3, autosomal recessive
Emery-Dreifuss muscular dystrophy atypical autosomal recessive
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
Emery-Dreifuss muscular dystrophy 4 with variable features
Emery-Dreifuss muscular dystrophy 5, autosomal dominant
Emery-Dreifuss muscular dystrophy 6, X-linked
Emery-Dreifuss muscular dystrophy 7, autosomal dominant
Encephalitis, acute, infection (viral)-induced, 11
An autosomal recessive disorder characterized by increased susceptibility to viral encephalitis affecting the brainstem and induced by neurotropic viruses, such as herpes simplex virus-1, influenza B virus or norovirus.
Encephalitis/encephalopathy, mild, with reversible myelin vacuolization
An autosomal dominant disease characterized by episodes of acute encephalitis associated with impaired consciousness, delirious behavior, seizures, and reversible splenial lesions observed on diffusion magnetic resonance imaging. Most patients completely recover and there are no neurologic sequelae. MMERV occurs in children and is frequently associated with a trigger, such as a febrile illness.
A sporadically occurring, neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, intracranial and intraspinal lipomas, and congenital abnormalities of the meninges. Seizures, spasticity, and intellectual disability can be present.
Encephalopathy due to defective mitochondrial and peroxisomal fission 1
Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission
Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission 1
A rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy. After birth, infants present in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. Other features include mildly elevated plasma concentration of very-long-chain fatty acids, lactic acidosis, microcephaly, deep-set eyes, optic atrophy and hypoplasia, and an abnormal gyral pattern in both frontal lobes associated with dysmyelination.
Encephalopathy due to defective mitochondrial and peroxisomal fission 2
An autosomal recessive disorder characterized by delayed psychomotor development, severe hypotonia with inability to walk, microcephaly, and abnormal signals in the basal ganglia. More variable features include early-onset seizures, optic atrophy, and peripheral neuropathy.
Encephalopathy, acute, infection-induced, 1, herpes-specific
Encephalopathy, acute, infection-induced, 1
Infection-induced acute encephalopathy 1
A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.
Encephalopathy, acute, infection-induced, 3
Encephalopathy acute infection-induced 3
A rapidly progressive encephalopathy manifesting in susceptible individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem.
Encephalopathy, acute, infection-induced, 4
Encephalopathy acute infection-induced 4
A severe neurologic complication of an infection. It manifests within days in otherwise healthy children after common viral infections, without evidence of viral infection of the brain or inflammatory cell infiltration. In affected children, high-grade fever is accompanied within 12 to 48 hours by febrile convulsions, often leading to coma, multiple-organ failure, brain edema, and high morbidity and mortality. The infections are usually viral, particularly influenza, although other viruses and even mycoplasma have been found to cause the disorder.
Encephalopathy, acute, infection-induced, 5, herpes-specific
Encephalopathy, acute, infection-induced, 5
Infection-induced acute encephalopathy 5
Encephalopathy, acute, infection-induced, 6, herpes-specific
Encephalopathy, acute, infection-induced, 6
Encephalopathy, acute, infection-induced, 7, herpes-specific
Encephalopathy, acute, infection-induced, 7
Infection-induced acute encephalopathy 7
Encephalopathy, acute, infection-induced, 8, herpes-specific
A rare, often fatal complication of herpes simplex infection, caused by virus spreading in the central nervous system. Disease manifestations include low-grade fever, severe headache, nausea, vomiting, and lethargy. Neurological features include confusion, acute memory disturbances, disorientation, behavioral changes, hemiparesis and seizures.
Encephalopathy, acute, infection-induced, 9
An autosomal recessive disorder characterized by infancy-onset of episodic neurodevelopmental regression in association with infection-induced febrile illness. Clinical features include poor overall growth, seizures, myoclonic jerks, microcephaly, ataxia, and cerebellar atrophy.
Encephalopathy, familial, with neuroserpin inclusion bodies
Familial encephalopathy with Collins bodies
A neurodegenerative disease clinically characterized by dementia. Additional features include intellectual decline, psychic seizures, progressive myoclonic epilepsy, and cerebral atrophy. Histologically, it is characterized by the presence of eosinophilic inclusion bodies (called Collins bodies) throughout the deeper layers of the cerebral cortex, leading to neuronal death.
Encephalopathy, neonatal severe, due to MECP2 mutations
A neurodevelopmental disorder characterized by severe neonatal encephalopathy, developmental delay, intellectual disability, microcephaly, seizures. Additional features include respiratory insufficiency and central hypoventilation, gastroesophageal reflux, axial hypotonia, hyperreflexia and dyskinetic movements.
Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities
An autosomal recessive disorder characterized by severe encephalopathy with neonatal onset, metabolic features including lactic acidosis, little or no psychomotor development, and brain abnormalities including cerebral atrophy, cysts, and white matter abnormalities.
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity
An autosomal recessive, progressive encephalopathy characterized by central nervous system atrophy and dysfunction, spasticity, microcephaly, global developmental delay, and hearing loss.
Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum
An autosomal recessive disease with neurodevelopmental and neurodegenerative features. PEBAT is characterized by early-onset cortical atrophy, hypomyelination, microcephaly, thin corpus callosum, delayed psychomotor development, developmental regression, intellectual disability, seizures, optic atrophy, muscle weakness and atrophy, spastic quadriplegia, and respiratory insufficiency due to hypotonia.
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy 1
An autosomal recessive severe neurometabolic disorder characterized by severe leukoencephalopathy usually associated with a trivial febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures. Disease course is rapidly progressive, leading to coma, global brain atrophy, and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions.
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2
Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis
An autosomal recessive disease characterized by progressive encephalopathy exacerbated by febrile illness and associated with severe neurodevelopmental delay, episodes of rhabdomyolysis, developmental regression, epilepsy and tetraplegia.
Encephalopathy, progressive, with amyotrophy and optic atrophy
An autosomal recessive, progressive, neurodegenerative encephalopathy with onset in infancy. Affected individuals manifest delayed psychomotor development, severe hypotonia, motor regression, spinal muscular atrophy, distal amyotrophy and weakness of all limbs, and intellectual disability of variable severity. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy.
Encephalopathy, progressive, with or without lipodystrophy
A neurodegenerative disease characterized by developmental regression of motor and cognitive skills in the first years of life, often leading to death in the first decade, hyperactive behavior, seizures, tremor and ataxic gait. Patients may show a mild or typical lipodystrophic appearance.
A condition characterized by multiple formation of enchondromas, benign neoplasms derived from mesodermal cells that form cartilage. Enchondromas remain within the substance of a cartilage or bone. Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to osteosarcoma.
Previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems.
A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
Endosteal hyperostosis autosomal dominant
Hyperostosis corticalis generalisata benign form of Worth with torus palatinus
An autosomal dominant sclerosing bone dysplasia clinically characterized by elongation of the mandible, increased gonial angle, flattened forehead, and the presence of a slowly enlarging osseous prominence of the hard palate (torus palatinus). Serum calcium, phosphorus and alkaline phosphatase levels are normal. Radiologically, it is characterized by early thickening of the endosteum of long bones, the skull and of the mandible. With advancing age, the trabeculae of the metaphysis become thickened. WENHY becomes clinically and radiologically evident by adolescence, does not cause deformity except in the skull and mandible, and is not associated with bone pain or fracture. Affected patients have normal height, proportion, intelligence and longevity.
Mesomelia of lower extremities with hand, foot, and brain anomalies
An autosomal recessive disorder characterized by marked mesomelic shortening of the lower limbs, severe hypoplasia of the tibia and fibula, absent talus, and rudimentary and short foot bones. Hands show short and malformed fingers with a missing digit, and nails are absent on some fingers. Affected individuals manifest neurologic symptoms including seizures and generalized hypotonia. Brain imaging reveals absence of the cerebellum and hypoplasia of the brain stem.
Mesomelia of lower extremities with hand and foot anomalies
An autosomal recessive disorder characterized by severe shortening and deformation of the legs and feet, 3/4 syndactyly of the hands, and toenails partially displaced to plantar surface. Radiographs show normal femora but severely shortened tibiae, triangular fibulae and malformed or absent bones in the feet. In addition, genitourinary anomalies have been observed.
Autosomal recessive retinopathy in which patients have increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. ESCS is also associated with visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration.
Life-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive.
Partial eosinophil peroxidase deficiency
Peroxidase and phospholipid deficiency in eosinophils
A rare abnormality without clinical symptoms characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix in eosinophils.
A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV1 inheritance is autosomal recessive.
A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV2 inheritance is autosomal recessive.
A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV3 inheritance is autosomal recessive.
A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV4 patients have decreased number of naive T cells, increased memory and effector T cells, and impaired T-cell receptor signaling. EV4 inheritance is autosomal recessive.
A form of epidermodysplasia verruciformis, a rare genodermatosis associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses, including the oncogenic HPV5. Infection leads to the early development of disseminated flat wart-like and pityriasis versicolor-like skin lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous cell carcinomas develop in about half of the patients, mainly on sun-exposed skin areas. EV5 patients shows T-cell lymphopenia, particularly affecting CD4+ T cells. EV5 inheritance is autosomal recessive.
Epidermolysis bullosa dystrophica, autosomal dominant
Albopapuloid dominant dystrophic epidermolysis bullosa
Autosomal dominant dystrophic epidermolysis bullosa
Epidermolysis bullosa dystrophica, Cockayne-Touraine type
Epidermolysis bullosa dystrophica, Pasini type
A group of autosomal dominant blistering skin diseases characterized by tissue separation which occurs below the dermal-epidermal basement membrane at the level of the anchoring fibrils. Various clinical types with different severity are recognized, ranging from severe mutilating forms to mild forms with limited and localized scarring, and less frequent extracutaneous manifestations.
Epidermolysis bullosa dystrophica, autosomal recessive
Autosomal recessive dystrophic epidermolysis bullosa
Epidermolysis bullosa dystrophica, generalized severe, autosomal recessive
Epidermolysis bullosa dystrophica, Hallopeau-Siemens type
A group of autosomal recessive blistering skin diseases characterized by tissue separation which occurs below the dermal-epidermal basement membrane at the level of the anchoring fibrils. Various clinical types with different severity are recognized, ranging from severe mutilating forms, such as epidermolysis bullosa dystrophica Hallopeau-Siemens type, to mild forms with limited localized scarring and less frequent extracutaneous manifestations. Mild forms include epidermolysis bullosa mitis and epidermolysis bullosa localisata.
Epidermolysis bullosa dystrophica, Bart type
Epidermolysis bullosa with congenital localized absence of skin and deformity of nails
An autosomal dominant form of dystrophic epidermolysis bullosa characterized by congenital localized absence of skin, skin fragility and deformity of nails.
Epidermolysis bullosa dystrophica, pretibial type
A form of dystrophic epidermolysis bullosa characterized by pretibial blisters that develop into prurigo-like hyperkeratotic lesions. It predominantly affects the pretibial areas, sparing the knees and other parts of the skin. Other clinical features include nail dystrophy, albopapuloid skin lesions, and hypertrophic scars without pretibial predominance. The phenotype shows considerable interindividual variability. Inheritance is autosomal dominant.
Epidermolysis bullosa dystrophica, with subcorneal cleavage
A bullous skin disorder with variable sized clefts just beneath the level of the stratum corneum. Clinical features include blisters, milia, atrophic scarring, nail dystrophy, and oral and conjunctival involvement, as seen in dystrophic epidermolysis bullosa.
A distinct clinical subtype of epidermolysis bullosa dystrophica. It is characterized by skin fragility, blistering, scar formation, intense pruritus and excoriated prurigo nodules. Onset is in early childhood, but in some cases is delayed until the second or third decade of life. Inheritance can be autosomal dominant or recessive.
Epidermolysis bullosa simplex 1A, generalized severe
Epidermolysis bullosa herpetiformis, Dowling-Meara type
Epidermolysis bullosa simplex, Dowling-Meara type
Epidermolysis bullosa simplex, generalized severe
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS1A is an autosomal dominant form characterized by generalized intraepidermal skin blistering that begins and is very prominent at birth. EBS1A may be life-threatening in the first year of life. Tendency to blistering diminishes in adolescence.
Epidermolysis bullosa simplex 1B, generalized intermediate
Epidermolysis bullosa simplex, Koebner type
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS1B is an autosomal dominant form characterized by generalized intraepidermal blistering beginning at birth. The tendency to blistering diminishes in adolescence, when it may become localized to hands and feet.
Epidermolysis bullosa simplex 1C, localized
Epidermolysis bullosa simplex, localized
Epidermolysis bullosa simplex, Weber-Cockayne type
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS1C is an autosomal dominant form with intraepidermal blistering mainly restricted to hands and feet beginning in infancy. Nails may be thick and dystrophic.
Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Epidermolysis bullosa simplex, autosomal recessive 1
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS1D is an autosomal recessive form characterized by blistering beginning at birth or early childhood. In some patients hands and feet are primarily affected, and in others blistering anywhere on the body may occur. In some patients the condition improves with age.
Epidermolysis bullosa simplex 2A, generalized severe
Epidermolysis bullosa simplex 2a, Dowling-Meara type
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS2A is an autosomal dominant, severe form characterized by extensive intraepidermal blistering from the time of birth with herpetiform marginal spreading and central healing. Oral mucosal involvement, nail dystrophy, onychogryposis, formation of milia, and palmoplantar hyperkeratosis are common features.
Epidermolysis bullosa simplex 2B, generalized intermediate
Epidermolysis bullosa simplex 2B, Koebner type
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS2B is an autosomal dominant form characterized by generalized blistering manifesting at birth. The tendency to blistering diminishes in adolescence, when it may become localized to hands and feet.
Epidermolysis bullosa simplex 2C, localized
Epidermolysis bullosa simplex 2C, Weber-Cockayne type
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS2C is an autosomal dominant form with intraepidermal blistering mainly restricted to hands and feet beginning in infancy. Nails may be thick and dystrophic.
Epidermolysis bullosa simplex 2D, generalized, intermediate or severe, autosomal recessive
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS2D is an autosomal recessive form characterized by widespread intraepidermal skin blistering and erosions from birth. Death may occur in the neonatal period.
Epidermolysis bullosa simplex 2E, with migratory circinate erythema
Epidermolysis bullosa simplex, with migratory circinate erythema
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS2E is an autosomal dominant form in which multiple vesicles are present from birth onward and acquire over time a typical migratory circinate pattern on an erythematous background. Postinflammatory hyperpigmentation develops gradually and may have a mottled pattern.
Epidermolysis bullosa simplex 2F, with mottled pigmentation
Epidermolysis bullosa simplex, with mottled pigmentation
Speckled hyperpigmentation with punctate palmoplantar keratoses and childhood blistering
A form of epidermolysis bullosa simplex, a group of skin fragility disorders characterized by skin blistering due to cleavage within the basal layer of keratinocytes, and erosions caused by minor mechanical trauma. There is a broad spectrum of clinical severity ranging from minor blistering on the feet, to subtypes with extracutaneous involvement and a lethal outcome. EBS2F is an autosomal dominant form characterized by generalized skin blistering of intermediate severity beginning at birth, with mottled or reticulate pigmentation developing gradually. Focal keratoses of palms and soles and dystrophic, thickened nails develop over time.
Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency
Epidermolysis bullosa simplex, autosomal recessive 2
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS3 is an autosomal recessive disorder characterized by skin blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques.
Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS4 is an autosomal recessive disorder characterized by mild skin fragility with onset at birth or in early childhood, associated with acral blistering with hemorrhagic crusts. Skin fragility improves with age in most patients, although mottled pigmentation may later develop on the trunk and proximal limbs.
Epidermolysis bullosa simplex 5A, Ogna type
Epidermolysis bullosa simplex, Ogna type
An autosomal dominant form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5A patients manifest generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, EBS5A is differentiated from classical epidermolysis bullosa simplex, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates.
Epidermolysis bullosa simplex 5B, with muscular dystrophy
Epidermolysis bullosa simplex and limb-girdle muscular dystrophy
Epidermolysis bullosa simplex with muscular dystrophy
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5B is an autosomal recessive disorder characterized by progressive muscular dystrophy associated with generalized skin blistering.
Epidermolysis bullosa simplex 5C, with pyloric atresia
Epidermolysis bullosa simplex with pyloric atresia
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5C is an autosomal recessive disorder characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy.
Epidermolysis bullosa simplex 5D, generalized intermediate, autosomal recessive
Epidermolysis bullosa simplex with nail dystrophy
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5D patients have generalized skin blistering that heals with scarring and hyperpigmentation, and severe nail dystrophy. Mucous membranes, heart, and muscle are spared.
Epidermolysis bullosa simplex 6, generalized, with scarring and hair loss
Epidermolysis bullosa simplex, generalized, with scarring and hair loss
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS6 is an autosomal dominant disorder presenting at birth with extensive skin defects on the extremities, leaving behind hypopigmentation and atrophy with a whirled pattern. Cutaneous fragility and generalized blistering persist during childhood and decrease in adulthood. Adult patients have dyspigmentation and atrophy of the skin, scars, follicular atrophoderma, sparse body hair, progressive diffuse alopecia of the scalp, diffuse palmoplantar keratoderma, and nail changes.
Epidermolysis bullosa simplex 7, with nephropathy and deafness
Nephropathy with pretibial epidermolysis bullosa and deafness
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS7 is an autosomal recessive disorder characterized by the association of skin blistering, hereditary nephritis, sensorineural deafness, and beta-thalassemia minor. Skin blistering is present at birth, particularly in the tibial area but also scattered on other parts of the body.
Epidermolysis bullosa, junctional 1A, intermediate
Epidermolysis bullosa atrophicans generalisata mitis
Epidermolysis bullosa junctionalis Disentis type
Epidermolysis bullosa junctionalis progressive
Epidermolysis bullosa junctionalis severe non-lethal
Generalized atrophic benign epidermolysis bullosa
Generalized junctional epidermolysis bullosa mitis
Non-Herlitz junctional epidermolysis bullosa
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. Junctional epidermolysis bullosa is characterized by blistering that occurs at the level of the lamina lucida in the skin basement membrane. JEB1A is an autosomal recessive, non-lethal, adult form characterized by life-long blistering of the skin, associated with hair and tooth abnormalities.
Epidermolysis bullosa, junctional 1B, severe
Epidermolysis bullosa, junctional, Herlitz type
Junctional epidermolysis bullosa Herlitz-Pearson type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. Junctional epidermolysis bullosa is characterized by blistering that occurs at the level of the lamina lucida in the skin basement membrane. JEB1B is an autosomal recessive, severe form characterized by bullous lesions appearing at birth, and extensive denudation of skin and mucous membranes that may be hemorrhagic. Death occurs usually within the first six months of life. Occasionally, children survive to teens.
Epidermolysis bullosa, junctional 2A, intermediate
Epidermolysis bullosa, junctional 2A, generalized intermediate
Epidermolysis bullosa, junctional 2A, non-Herlitz type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB2A is an autosomal recessive, intermediate form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. In intermediate forms of junctional epidermolysis bullosa, blistering does not lead to the formation of chronic granulation tissue and does not affect the lifespan of affected individuals. Nail dystrophy and dental enamel defects are present. Scarring or non-scarring alopecia and diffuse hair loss may occur.
Epidermolysis bullosa, junctional 2B, severe
Epidermolysis bullosa, junctional 2B, generalized severe
Epidermolysis bullosa, junctional 2B, Herlitz type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB2B is an autosomal recessive form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. It belongs to the severe spectrum of junctional epidermolysis bullosa (previously known as generalized severe or Herlitz type), characterized by onset of blistering over large regions of the body at birth or in early infancy. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Other complications can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities, dental enamel defects, and alopecia. Severe, junctional forms are associated with death in the first 6 to 24 months of life.
Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB2C is an autosomal recessive, severe form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. JEB2C manifestations appear in early infancy and include hoarse cry, skin ulceration, nail dystrophy with recurrent loss of toenails and fingernails, and conjunctival scarring. Some patients have amelogenesis imperfecta. Death in childhood is common.
Epidermolysis bullosa, junctional 3A, intermediate
Epidermolysis bullosa, junctional 3A, generalized intermediate
Epidermolysis bullosa, junctional 3A, non-Herlitz type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB3A is an autosomal recessive, intermediate form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. In intermediate forms of junctional epidermolysis bullosa, blistering does not lead to the formation of chronic granulation tissue and does not affect the lifespan of affected individuals. Nail dystrophy and dental enamel defects are present. Scarring or non-scarring alopecia and diffuse hair loss may occur.
Epidermolysis bullosa, junctional 3B, severe
Epidermolysis bullosa, junctional 3B, generalized severe
Epidermolysis bullosa, junctional 3B, Herlitz type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB3B is an autosomal recessive form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. It belongs to the severe spectrum of junctional epidermolysis bullosa (previously known as generalized severe or Herlitz type), characterized by onset of blistering over large regions of the body at birth or in early infancy. Blistering also affects the mucous membranes, such as the moist lining of the mouth and digestive tract, which can make it difficult to eat and digest food. The extensive blistering leads to scarring and the formation of red, bumpy patches called granulation tissue. Other complications can include fusion of the fingers and toes, abnormalities of the fingernails and toenails, joint deformities, dental enamel defects, and alopecia. Severe, junctional forms are associated with death in the first 6 to 24 months of life.
Epidermolysis bullosa, junctional 4, intermediate
Epidermolysis bullosa, generalized atrophic benign
Epidermolysis bullosa, junctional, localisata variant
Epidermolysis bullosa, junctional 4, non-Herlitz type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB4 is an autosomal recessive, intermediate form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. In intermediate forms of junctional epidermolysis bullosa, blistering does not lead to the formation of chronic granulation tissue and does not affect the lifespan of affected individuals. Nail dystrophy and dental enamel defects are present. Scarring or non-scarring alopecia and diffuse hair loss may occur. JEB4 patients manifest blisters at birth or shortly afterward. Blisters may heal with atrophic scarring and variable hypo- or hyperpigmentation. Oral mucosa may be involved.
Epidermolysis bullosa, junctional 5A, intermediate
Epidermolysis bullosa, junctional 5A, generalized intermediate
Epidermolysis bullosa, junctional 5A, non-Herlitz type
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB5A is an autosomal recessive, intermediate form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. In intermediate forms of junctional epidermolysis bullosa, blistering does not lead to the formation of chronic granulation tissue and does not affect the lifespan of affected individuals. Nail dystrophy and dental enamel defects are present. Scarring or non-scarring alopecia and diffuse hair loss may occur.
Epidermolysis bullosa, junctional 5B, with pyloric atresia
Aplasia cutis congenita with gastrointestinal atresia
Epidermolysis bullosa letalis, with pyloric atresia
Junctional epidermolysis bullosa with pyloric atresia
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. Junctional epidermolysis bullosa is characterized by blistering that occurs at the level of the lamina lucida in the skin basement membrane. JEB5B is an autosomal recessive, severe, frequently lethal form with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa.
Epidermolysis bullosa, junctional 6, with pyloric atresia
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB6 is an autosomal recessive form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. Clinical manifestations include severe blistering, atrophic scarring, nail dystrophy, and pyloric atresia. Congenital absence of skin (aplasia cutis congenita) is common, and ear anomalies are also relatively common. Disease course is usually severe and often lethal in the neonatal period.
Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital
A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB7 is an autosomal recessive form associated with congenital nephrotic syndrome and interstitial lung disease. The respiratory and renal features predominate, and lung involvement accounts for the lethal course of the disease.
Epidermolysis bullosa, lethal acantholytic
Lethal acantholytic epidermolysis bullosa
A form of epidermolysis bullosa characterized by severe fragility of skin and mucous membranes. The phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. Typical features include universal alopecia, neonatal teeth, and nail loss. Histopathology of the skin shows suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus.
Bullous congenital ichthyosiform erythroderma
Bullous erythroderma ichthyosiformis congenita of Brocq
An autosomal dominant skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop.
A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Some individuals manifest febrile seizures. Absence seizures may either remit or persist into adulthood.
A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood.
Epilepsy, early-onset, vitamin B6-dependent
An autosomal recessive neurologic disorder characterized by seizures responsive to treatment with activated vitamin B6 and/or pyridoxine. Most patients show delayed psychomotor development, intellectual disability and learning disability. Seizures onset is in the first days or months of life.
Epilepsy, early-onset, with or without developmental delay
An autosomal dominant neurologic disorder characterized by early onset of generalized tonic-clonic seizures associated with sharp wave and sharp slow wave discharges on EEG. Some EPEDD patients have normal psychomotor development and normal brain imaging, whereas others may show developmental delay associated with abnormalities on brain imaging.
Benign adult familial myoclonic epilepsy 1
Cortical myoclonic tremor with epilepsy, familial, 1
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME1 inheritance is autosomal dominant.
Benign adult familial myoclonic epilepsy 2
Cortical myoclonic tremor with epilepsy, familial, 2
Cortical myoclonus and epilepsy, autosomal dominant
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME2 inheritance is autosomal dominant.
Cortical myoclonic tremor with epilepsy, familial, 3
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME3 inheritance is autosomal dominant.
Cortical myoclonic tremor with epilepsy, familial, 4
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME4 inheritance is autosomal dominant.
Cortical myoclonic tremor with epilepsy, familial, 5
Familial cortical myoclonic tremor with epilepsy 5
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME5 is characterized by onset of seizures in adolescence, followed by the development of cortical myoclonic tremor later in life. Inheritance is autosomal recessive.
Benign adult familial myoclonic epilepsy 6
Cortical myoclonic tremor with epilepsy, familial, 6
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME6 inheritance is autosomal dominant.
Benign adult familial myoclonic epilepsy 27
Cortical myoclonic tremor with epilepsy, familial, 7
A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME7 inheritance is autosomal dominant.
Epilepsy, familial focal, with variable foci 1
An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions in different family members. Many patients have an aura and show automatisms during the seizures, whereas others may have nocturnal seizures. There is often secondary generalization. Some patients show abnormal interictal EEG, and some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. Penetrance of the disorder is incomplete.
Epilepsy, familial focal, with variable foci 2
An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete.
Epilepsy, familial focal, with variable foci 3
Epilepsy, familial focal, with variable foci 4
An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. FFEVF4 is characterized by onset of focal seizures in the first years of life.
Lateral temporal lobe epilepsy autosomal dominant
A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature.
Epilepsy, focal, with speech disorder and with or without impaired intellectual development
Benign epilepsy of childhood with centrotemporal spikes
Continuous spike and waves during slow-wave sleep syndrome
An autosomal dominant, highly variable neurologic disorder. Features range from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and intellectual disability to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. The disorder encompasses several clinical entities, including Landau-Kleffner syndrome, epileptic encephalopathy with continuous spike and wave during slow-wave sleep, autosomal dominant rolandic epilepsy, intellectual disability and speech dyspraxia, and benign epilepsy with centrotemporal spikes.
Susceptibility to idiopathic generalized epilepsy 10
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.
Susceptibility to idiopathic generalized epilepsy 11
Susceptibility to idiopathic generalized epilepsy 12
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. In some EIG12 patients seizures may remit with age.
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures.
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures.
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG15 is characterized by onset of variable types of seizures in the first decade of life.
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG16 is characterized by onset of seizures soon after birth or in the first years of life.
A form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. Both autosomal dominant and autosomal recessive EIG17 inheritance have been reported.
An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG18 is characterized by onset of myoclonic seizures in infancy. Although the seizures remit, some patients may have later speech or cognitive impairment.
Susceptibility to idiopathic generalized epilepsy 6
Susceptibility to idiopathic generalized epilepsy 8
A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures.
Susceptibility to idiopathic generalized epilepsy 9
Autosomal dominant nocturnal frontal lobe epilepsy
An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
Familial epilepsy with nocturnal wandering and ictal fear
An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking.
An autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations and/or intellectual disability. The phenotype is more severe than observed in other genetic forms of nocturnal frontal lobe epilepsy.
Myoclonic epilepsy of Unverricht and Lundborg
Progressive myoclonic epilepsy Unverricht-Lundborg type
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM1 is an autosomal recessive form characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The onset, occurring between 6 and 13 years of age, is characterized by convulsions. Myoclonus begins 1 to 5 years later. The twitchings occur predominantly in the proximal muscles of the extremities and are bilaterally symmetrical, although asynchronous. At first small, they become late in the clinical course so violent that the victim is thrown to the floor. Mental deterioration and eventually dementia develop.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM10 is an autosomal recessive form characterized by progressive dysarthria, myoclonus, ataxia, cognitive decline, psychosis, dementia and spasticity, with onset in childhood. There is variability between patients.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM11 is an autosomal dominant form. Clinical features include normal or mildly delayed early development, developmental regression after seizures onset, inability to walk, severely impaired intellectual development, poor or absent speech, spasticity, ataxia, and intention tremor. Brain imaging shows cerebellar atrophy in some patients.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM12 is an autosomal recessive form characterized by onset of tonic-clonic seizures and/or myoclonus in the second decade of life. Affected individuals develop cerebellar ataxia associated with progressive cerebral and cerebellar atrophy on brain imaging. Most patients lose ambulation and become wheelchair-bound. Additional more variable features include mild cognitive dysfunction or psychiatric manifestations, such as depression or anxiety.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM1B is an autosomal recessive form characterized by myoclonus that progressed in severity over time, tonic-clonic seizures and ataxia.
Progressive myoclonic epilepsy Lafora type
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM2 is an autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum.
Epilepsy, progressive myoclonic 3, with or without intracellular inclusions
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM3 is an autosomal recessive, severe, form with early onset. Multifocal myoclonic seizures begin between 16 and 24 months of age after normal initial development. Neurodegeneration and regression occur with seizure onset. Other features include intellectual disability, dysarthria, truncal ataxia, and loss of fine finger movements. EEG shows slow dysrhythmia, multifocal and occasionally generalized epileptiform discharges. In some patients, ultrastructural findings on skin biopsies identify intracellular accumulation of autofluorescent lipopigment storage material, consistent with neuronal ceroid lipofuscinosis.
Epilepsy, progressive myoclonic 4, with or without renal failure
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM4 is an autosomal recessive form associated with renal failure in some cases. Cognitive function is preserved.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM6 is an autosomal recessive form characterized by onset of ataxia in the first years of life, followed by action myoclonus and seizures later in childhood, and loss of independent ambulation in the second decade. Cognition is not usually affected, although mild memory difficulties may occur in the third decade.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM7 is an autosomal dominant form characterized by myoclonic epilepsy apparent in the first or second decades of life. Cognitive function may decline in some patients.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM8 is an autosomal recessive form characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment.
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM9 is an autosomal recessive form characterized by myoclonus, tonic-clonic seizures, ataxia, and delayed psychomotor development.
Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp
An autosomal recessive neurologic disorder characterized by onset of focal seizures in infancy and exercise-induced dystonia in childhood. Clinical features include involuntary movements and difficulties with fine motor skills of the hand.
Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders
Epilepsy, X-linked, with reflex bathing seizures
A neurologic disorder characterized by variable combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behavior.
Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features
A neurologic disorder characterized by variable combinations of epileptic seizure, and a varying degree of intellectual disability and developmental delay. Some patients have dysmorphic facial features or mild skeletal anomalies. In general, males are more severely affected than females, although there is evidence for incomplete penetrance in both sexes.
Epileptic encephalopathy, infantile or early childhood, 1
A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE1 is an autosomal dominant condition with onset of seizures between the first weeks and first years of life.
Epileptic encephalopathy, infantile or early childhood, 2
A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE2 is an autosomal dominant condition with variable age at seizure onset, ranging from early infancy to 6 years.
Epileptic encephalopathy, infantile or early childhood, 3
A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE3 is an autosomal dominant form characterized by onset of seizures in the first years of life.The severity of the phenotype is highly variable: some patients may be non-verbal and non-ambulatory with spastic quadriparesis and poor eye contact, whereas others have moderate intellectual disability.
An overgrowth syndrome characterized by tall stature, long hands and feet with arachnodactyly, macrodactyly of the great toes, scoliosis, coxa valga and slipped capital femoral epiphysis.
A form of multiple epiphyseal dysplasia, a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. EDM7 inheritance is autosomal recessive.
An autosomal dominant disorder characterized by brief episodes of ataxia and dysarthria. Neurological examination during and between the attacks demonstrates spontaneous, repetitive discharges in the distal musculature (myokymia) that arise from peripheral nerve. Nystagmus is absent.
Acetazolamide-responsive hereditary paroxysmal cerebellar ataxia
An autosomal dominant disorder characterized by acetozolamide-responsive attacks of ataxia, migraine-like symptoms, interictal nystagmus, and cerebellar atrophy.
A disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia.
A disorder characterized by episodic ataxia, seizures, migraine and alternating hemiplegia.
An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development.
An autosomal dominant neurologic condition characterized by recurrent and brief attacks of abnormal involuntary movements, triggered by sudden voluntary movement. These attacks usually have onset during childhood or early adulthood and can involve dystonic postures, chorea, or athetosis.
An autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress. The period of intense pain is accompanied by breathing difficulties, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall. Affected individuals do not manifest altered pain sensitivity outside the episodes.
An autosomal dominant neurologic disorder characterized by adult-onset of paroxysmal pain mainly affecting the distal lower extremities.
An autosomal dominant neurologic disorder characterized by paroxysmal pain mainly affecting the distal lower extremities and occasionally the upper body, especially the joints of fingers and arms. The pain is exacerbated with fatigue.
A corneal dystrophy characterized by recurrent episodes of epithelial erosions from childhood, with occasional impairment of vision. Most patients have attacks of redness, photophobia, epiphora, and ocular pain. Exposure to sunlight or draught, dust and smoke and lack of sleep can precipitate attacks.
Autosomal dominant benign erythrocytosis
An autosomal dominant disorder characterized by elevated hemoglobin and hematocrit, hypersensitivity of erythroid progenitors to erythropoietin, erythropoietin low serum levels, and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia.
Autosomal recessive benign erythrocytosis
An autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events.
An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.
An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts.
An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit. Some patients have increased serum erythropoietin levels.
Diphosphoglycerate mutase deficiency of erythrocyte
Erythrocytosis due to bisphosphoglycerate mutase deficiency
An autosomal recessive disorder characterized by elevated serum hemoglobin and hematocrit, and biphosphoglycerate mutase deficiency. ECYT8 affected individuals manifest hemolytic anemia and splenomegaly.
Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE
Severe dermatitis, multiple allergies, and metabolic wasting syndrome
A syndrome characterized by severe dermatitis, multiple allergies and metabolic wasting. Clinical features include erythroderma, yellowish papules and plaques arranged at the periphery of the palms, along the fingers and over weight-bearing areas of the feet, skin erosions and scaling, and hypotrichosis. Additionally, patients manifest severe food allergies, elevated immunoglobulin E (IgE) levels and recurrent infections with marked metabolic wasting.
Erythrokeratodermia variabilis et progressiva 1
Congenital familial erythrokeratodermia figurata in plaques
Erythrokeratodermia progressive symmetric
Erythrokeratodermia variabilis et progressiva
Erythrokeratodermia variabilis Mendes da Costa type
Erythrokeratodermia variabilis with erythema gyratum repens
Keratosis palmoplantaris transgrediens et progrediens
Transgrediens et progrediens palmoplantar keratoderma
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.
Erythrokeratodermia variabilis et progressiva 2
Erythrokeratodermia variabilis et progressiva 3
Erythrokeratodermia variabilis et progressiva 4
Erythrokeratodermia variabilis et progressiva 5
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP5 inheritance is autosomal recessive.
Erythrokeratodermia variabilis et progressiva 6
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP6 inheritance is autosomal dominant.
Erythrokeratodermia variabilis et progressiva 7
A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP7 is an autosomal recessive form characterized by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet, as well as erythematous annular skin lesions. Pruritus, woolly hair, and dystrophic nails may also be present.
An autosomal dominant myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood. Disease penetrance is incomplete.
Erythropoietic protoporphyria, X-linked dominant
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. XLDPT is characterized biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.
A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.
A condition in which blood pressure is consistently higher than normal with no identifiable cause.
A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present.
Autosomal recessive disorder characterized by neurodevelopmental delay and regression, recurrent petechiae, acrocyanosis, diarrhea, leading to death in the first decade of life. It is also associated with persistent lactic acidemia and ethylmalonic and methylsuccinic aciduria.
Epiphyseal and vertebral dysplasia, microtia, and flat nose, plus associated malformations
An autosomal recessive syndrome characterized by epiphyseal and vertebral dysplasia, prenatal-onset short stature, a distinct craniofacial phenotype with microtia, a flat facial profile with flat nose and triangular nares, cardiac malformations, and additional findings such as anal atresia, hypodontia, aplasia cutis, and others.
A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors.
Exercise intolerance, riboflavin-responsive
A riboflavin-responsive form of exercise intolerance, a condition characterized by failure to maintain an expected level of force during sustained or repeated muscle contraction, resulting in an overwhelming sense of tiredness, lack of energy and feeling of exhaustion. RREI transmission pattern is consistent with autosomal recessive inheritance.
A disorder characterized by accumulation of abnormal fibrillar deposits in the anterior segment of the eye. In addition to being a cause of glaucoma and glaucomatous optic neuropathy, exfoliation syndrome has also been associated with lens zonule weakness, cataract formation, and systemic vascular complications due to deposition of exfoliation material in extraocular tissues.
Exocrine pancreatic insufficiency dyserythropoietic anemia and calvarial hyperostosis
Patients present with pancreatic insufficiency, intestinal malabsorption, failure to thrive, and anemia soon after birth.
Extraoral halitosis due to methanethiol oxidase deficiency
Extraoral halitosis due to MTO deficiency
Extraoral halitosis with dimethylsulfoxiduria
An autosomal recessive malodor condition characterized by extraoral blood-borne halitosis resulting from the accumulation of sulfur-containing metabolites. In extraoral blood-borne halitosis, malodorant compounds are carried to the lungs, where they enter the breath. Affected individuals have a cabbage-like breath odor, high levels of methanethiol and dimethylsulfide in oral and nasal breath, and elevated urinary excretion of dimethylsulfoxide in the absence of intake of dimethylsulfide-containing food or use of sulfur-containing medication, lower-gastrointestinal problems, and known metabolic defects, such as methionine adenosyltransferase deficiency and tyrosinemia.
Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities.
Oculomaxillofacial dysplasia with oblique facial clefts
A rare form of facial clefting. A facial cleft is any of the fissures between the embryonic prominences that normally unite to form the face.
Facial dysmorphism, hypertrichosis, epilepsy, intellectual and developmental delay, and gingival overgrowth syndrome
An autosomal dominant syndrome characterized by delayed motor and intellectual development, poor speech, seizures, generalized hypertrichosis and facial dysmorphic features, including hypotonic facies, bitemporal narrowing, micrognathia, deep-set eyes, bushy eyebrows and long eyelashes, low-set ears, short deep philtrum, gingival overgrowth, prominent upper and lower vermilion, and everted upper lip.
Facial dysmorphism, immunodeficiency, livedo, and short stature
A syndrome characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, and immunodeficiency resulting in recurrent infections. Growth impairment is observed during early childhood and results in variable short stature in adulthood.
Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs
Ectopia lentis, spontaneous filtering blebs, and craniofacial dysmorphism
A syndrome characterized by dislocated crystalline lenses and anterior segment abnormalities in association with a distinctive facies involving flat cheeks and a beaked nose. Some affected individuals develop highly unusual non-traumatic conjunctival cysts (filtering blebs).
Facial palsy, congenital, with ptosis and velopharyngeal dysfunction
An autosomal dominant congenital disorder characterized by non-progressive bilateral facial palsy, velopharyngeal dysfunction presenting with varying degrees of hypomimia, rhinophonia and impaired gag reflex, and bilateral ptosis.
Facial paresis, hereditary congenital, 3
A form of facial paresis, a disease characterized by isolated dysfunction of the facial nerve (CN VII). HCFP3 patients are affected by bilateral facial palsy, facial muscle weakness of muscles innervated by CN VII, hearing loss, and strabismus.
Facioscapulohumeral muscular dystrophy 1
Facioscapulohumeral muscular dystrophy type 1A
A degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles.
Facioscapulohumeral muscular dystrophy 2, digenic
Digenic facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy type 1B
Facioscapulohumeral muscular dystrophy 3, digenic
A form of facioscapulohumeral muscular dystrophy, a degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. FSHD3 is a digenic form characterized by adult onset of proximal muscle weakness affecting the face, neck, scapular muscles, and upper and lower limbs. Muscle involvement is usually asymmetric, and other muscle groups may become involved with progression of the disease.
Facioscapulohumeral muscular dystrophy 4, digenic
A digenic form of facioscapulohumeral muscular dystrophy, a degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. With disease progression, other muscles may also become affected. There is significant clinical variability and incomplete penetrance.
A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.
Factor V and factor VIII combined deficiency 1
Familial multiple coagulation factor deficiency I
Multiple coagulation factor deficiency 1
Multiple coagulation factor deficiency I
A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal.
Factor V and factor VIII combined deficiency 2
Multiple coagulation factor deficiency 2
A blood coagulation disorder leading to a hemorrhagic diathesis known as parahemophilia.
A hemorrhagic disease with variable presentation. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Finally, numerous subjects are completely asymptomatic despite very low factor VII levels.
A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.
Plasma thromboplastin antecedent deficiency
A hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.
An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).
An autosomal recessive hematologic disorder characterized by a life-long bleeding tendency, impaired wound healing and spontaneous abortion in affected women.
An autosomal dominant cancer predisposition syndrome characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.
Adenomas multiple colorectal autosomal recessive
Colorectal adenomatous polyposis autosomal recessive
A condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma.
A form of familial adenomatous polyposis, a condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma.
A form of familial adenomatous polyposis, a condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma. FAP4 inheritance is autosomal recessive.
Familial apolipoprotein gene cluster deletion syndrome
An autosomal dominant disorder of lipoprotein metabolism. Affected individuals do not produce ApoA-I, ApoC-III and ApoA-IV lipoproteins, have marked plasma high density lipoprotein (HDL) deficiency, and manifest premature atherosclerosis and coronary artery disease.
Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome
An inherited cancer predisposition syndrome characterized by an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer.
Familial cold autoinflammatory syndrome 1
Cryopyrin-associated periodic syndrome 1
Familial cold-induced autoinflammatory syndrome
A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis.
Familial cold autoinflammatory syndrome 2
A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold.
Familial cold autoinflammatory syndrome 3
Antibody deficiency and immune dysregulation PLACG2-associated
An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B-cells, defective B-cells, increased susceptibility to infection, and increased risk of autoimmune disorders.
Familial cold autoinflammatory syndrome 4
A form of autoinflammatory syndrome, a rare autosomal dominant systemic disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold.
Rare autosomal dominant bone disorder characterized by focal areas of increased bone remodeling. The osteolytic lesions develop usually in the long bones during early adulthood. FEO is often associated with early-onset deafness and loss of dentition.
A condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy.
Familial hyperinsulinemic hypoglycemia 1
Persistent hyperinsulinemic hypoglycemia of infancy
Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
Familial hyperinsulinemic hypoglycemia 2
Familial hyperinsulinemic hypoglycemia 3
Familial hyperinsulinemic hypoglycemia 4
Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion.
Familial hyperinsulinemic hypoglycemia 5
Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels.
Familial hyperinsulinemic hypoglycemia 6
Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. In HHF6 elevated oxidation rate of glutamate to alpha-ketoglutarate stimulates insulin secretion in the pancreatic beta cells, while they impair detoxification of ammonium in the liver.
Familial hyperinsulinemic hypoglycemia 7
Exercise-induced hyperinsulinemic hypoglycemia
Dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load.
A subtype of idiopathic epilepsy starting in early infancy and manifesting as myoclonic seizures, febrile convulsions, and tonic-clonic seizures.
In FMPP the receptor is constitutively activated.
Familial Mediterranean fever, autosomal dominant
A hereditary periodic fever syndrome characterized by periodic fever, serosal inflammation and pain in the abdomen, chest or joints as seen also in the autosomal recessive form of the disease. It is associated with reactive renal amyloidosis and characterized by colchicine unresponsiveness.
Familial Mediterranean fever, autosomal recessive
A hereditary periodic fever syndrome characterized by recurrent episodic fever, serosal inflammation and pain in the abdomen, chest or joints. It is frequently complicated by reactive amyloidosis, which leads to renal failure and can be prophylactically treated with colchicine.
Familial multiple endocrine neoplasia type I
Autosomal dominant disorder characterized by tumors of the parathyroid glands, gastro-intestinal endocrine tissue, the anterior pituitary and other tissues. Cutaneous lesions and nervous-tissue tumors can exist. Prognosis in MEN1 patients is related to hormonal hypersecretion by tumors, such as hypergastrinemia causing severe peptic ulcer disease (Zollinger-Ellison syndrome, ZES), primary hyperparathyroidism, and acute forms of hyperinsulinemia.
Cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.
Familial paroxysmal ventricular fibrillation 1
Susceptibility to ventricular fibrillation during myocardial infarction
Ventricular fibrillation, paroxysmal familial, 1
A cardiac arrhythmia marked by fibrillary contractions of the ventricular muscle due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricle and by absence of atrial activity.
Familial paroxysmal ventricular fibrillation 2
Familial platelet disorder with associated myeloid malignancy
Autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.
Uroporphyrinogen decarboxylase deficiency
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Familial porphyria cutanea tarda is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage.
Scaphocephaly, maxillary retrusion, and impaired intellectual development
An autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.
Considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some severe FANCB cases manifest features of VACTERL syndrome with hydrocephalus.
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. Some individuals affected by Fanconi anemia of complementation group P have skeletal anomalies.
Estren-Dameshek variant of Fanconi anemia
Estren-Dameshek variant of Fanconi pancytopenia
A form of Fanconi anemia, a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant.
A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS2 inheritance is autosomal recessive.
A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS3 inheritance is autosomal dominant.
Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young
An autosomal dominant disease characterized by Fanconi syndrome associated with a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Fanconi syndrome is a proximal tubulopathy resulting in generalized aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricemia. Some FRTS4 patients have nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcemia, and hypermagnesemia.
Fanconi renotubular syndrome, Acadian variant
A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS5 is an autosomal recessive mitochondrial disorder characterized by proximal renotubular dysfunction from birth, followed by progressive kidney disease and pulmonary fibrosis.
Fanconi syndrome with intestinal malabsorption and galactose intolerance
Hepatic glycogenosis with amino aciduria and glucosuria
Hepatic glycogenosis with Fanconi nephropathy
Hepatorenal glycogenosis with renal Fanconi syndrome
Rare, well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.
N-laurylsphingosine deacylase deficiency
An autosomal recessive lysosomal storage disorder characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, and marked accumulation of ceramide in lysosomes. Disease severity is variable. The most severe disease subtype is a rare neonatal form with death occurring before 1 year of age.
Autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.
An autosomal dominant disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphic features.
A rare neurological disease characterized by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. It may present in childhood with severe neurological deterioration with hypotonia, respiratory insufficiency leading to premature death, or later in life with bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles.
Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy.
Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. FEB2 transmission pattern is consistent with autosomal dominant inheritance.
Digital anomalies with short palpebral fissures and atresia of esophagus or duodenum
Microcephaly-oculo-digito-esophageal-duodenal syndrome
A syndrome characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, intellectual disability, and limb malformations. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described.
Brachydactyly with short stature and microcephaly
A syndrome characterized by microcephaly, short stature, and digital abnormalities including brachydactyly, brachymesophalangy of the second and fifth fingers, hypoplastic thumbs of variable severity, and cutaneous syndactyly of the toes.
Ferguson-Bonni neurodevelopmental syndrome
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, and hypotonia with early motor delay. Additional features may include dysmorphic facies, mild skeletal abnormalities, and hearing loss.
Arthrogryposis multiplex congenita with pulmonary hypoplasia
A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS1 inheritance is autosomal recessive.
A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS2 inheritance is autosomal recessive.
A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS3 inheritance is autosomal recessive.
A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. FADS4 inheritance is autosomal recessive.
Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies
An autosomal recessive disease characterized by fetal akinesia, and generalized joint contractures and arthrogryposis at birth. Affected newborns have severe respiratory insufficiency and significant dysmorphic facial features. Malformations of cortical development are seen on brain imaging, most commonly polymicrogyria or other gyral anomalies. Death usually occurs in infancy.
FG syndrome (FGS) is an X-linked disorder characterized by intellectual disability, relative macrocephaly, hypotonia and constipation.
A severe short-limbed skeletal dysplasia characterized by broad long-bone metaphyses, pear-shaped vertebral bodies, and characteristic morphology of the growth plate, in which the chondrocytes have a fibroblastic appearance and there are regions of fibrous cartilage extracellular matrix. Clinical features include a flat midface with a small nose and anteverted nares, significant shortening of all limb segments but relatively normal hands and feet, and a small bell-shaped thorax with a protuberant abdomen.
A severe skeletal dysplasia characterized by a flat midface, short long bones, short ribs with broad metaphyses, and vertebral bodies that show distinctive hypoplastic posterior ends and rounded anterior ends, giving the vertebral bodies a pinched appearance on lateral radiographic views. The chest is small, causing perinatal respiratory problems which usually, but not always, result in lethality. Affected individuals who survive the neonatal period have high myopia, mild to moderate hearing loss, and severe skeletal dysplasia.
A rare autosomal dominant connective tissue disorder resulting in skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to a debilitating ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible.
A form of hereditary gingival fibromatosis, a rare condition characterized by a slow, progressive overgrowth of the gingiva. The excess gingival tissue can cover part of or the entire crown, and can result in diastemas, teeth displacement, or retention of primary or impacted teeth. GINGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.
An autosomal dominant form of hereditary gingival fibromatosis, a rare condition characterized by a slow, progressive overgrowth of the gingiva. The excess gingival tissue can cover part of or the entire crown, and can result in diastemas, teeth displacement, or retention of primary or impacted teeth.
An autosomal dominant vascular disorder with incomplete penetrance, characterized by fibrous tissue and webs developing in the artery wall and leading to multiple arterial stenoses. Patients with multifocal fibromuscular dysplasia can develop arterial tortuosity, macroaneurysms, and dissections. Arterial rupture may occur.
Fibrosis of extraocular muscles, congenital, 1
Blepharoptosis with absent eye movements
A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Patients affected by congenital fibrosis of extraocular muscles type 1 show an absence of the superior division of the oculomotor nerve (cranial nerve III) and corresponding oculomotor subnuclei.
Fibrosis of extraocular muscles, congenital, 2
Congenital fibrosis of extraocular muscles autosomal recessive
A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 2 may result from the defective development of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei.
Fibrosis of extraocular muscles, congenital, 3A
Congenital fibrosis of extraocular muscles 3A with or without extraocular involvement
A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases, the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy.
Fibrosis of extraocular muscles, congenital, 3B
Fibrosis of extraocular muscles, congenital, 5
An ocular motility disorder characterized by congenital dysinnervation of various cranial nerves to ocular muscles. Clinical features are ophthalmoplegia, anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head.
Fibrosis, neurodegeneration, and cerebral angiomatosis
An autosomal recessive, early-onset and fatal disorder clinically characterized by progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic hemolytic anemia and transient liver dysfunction. Death occurs in the first years of life due to respiratory failure. Post-mortem neuropathological examination reveals increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and granuloma-like lesions are observed in the lungs. Hepatomegaly, steatosis and collagen accumulation are detected in the liver.
Defect in lectin complement activation pathway, 3
Immunodeficiency due to ficolin 3 deficiency
A disorder characterized by immunodeficiency, recurrent infections, brain abscesses and recurrent warts on the fingers. Affected individuals have normal levels of lymphocytes, normal T-cell responses, and normal antibodies, but a selective deficient antibody response to pneumococcal polysaccharide vaccine.
A rare disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities.
A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea ('fish-eye').
An autosomal recessive condition associated with a distinctive retinal appearance and no apparent visual or electrophysiologic deficits. Affected individuals are asymptomatic, but fundus examination reveals a striking pattern of diffuse, yellow-white, fleck-like lesions extending to the far periphery of the retina but sparing the foveal region.
A rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips.
Cortical dysplasia of Taylor, dysplasia only
Cortical dysplasia of Taylor with balloon cells
Cortical dysplasia of Taylor without balloon cells
A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells.
Focal cortical dysplasia of Taylor balloon cell type
Subtype of cortical dysplasias linked to chronic intractable epilepsy. Cortical dysplasias display a broad spectrum of structural changes, which appear to result from changes in proliferation, migration, differentiation, and apoptosis of neuronal precursors and neurons during cortical development.
A rare congenital ectomesodermal disorder characterized by a combination of skin defects, skeletal abnormalities, and ocular anomalies. Affected individuals have patchy dermal hypoplasia, often in a distribution pattern following the Blaschko lines, and areas of subcutaneous fat herniation or deposition of fat into the dermis. In addition, sparse and brittle hair, hypoplastic nails and papillomas have been described. Skeletal abnormalities usually comprise syndactyly, ectrodactyly, and brachydactyly, and in some cases osteopathia striata has been seen. Patients frequently have ocular anomalies, including microphthalmia/ anophthalmia, coloboma, pigmentary and vascularization defects of the retina. Dental abnormalities are often present.
Focal facial dermal dysplasia 3, Setleis type
A form of focal facial dermal dysplasia, a group of developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD3 is characterized by distinctive bitemporal scar-like depressions resembling forceps marks, and additional facial features, including a coarse and leonine appearance, absent eyelashes on both lids or multiple rows on the upper lids, absent Meibomian glands, slanted eyebrows, chin clefting, and hypo- or hyperpigmentation of the skin. Histologically, the bitemporal lesion is an ectodermal dysplasia with near absence of subcutaneous fat, suggesting insufficient migration of neural crest cells into the frontonasal process and the first branchial arch.
A form of focal facial dermal dysplasia, a group of developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. Skin defects occur at the sites of facial fusion during embryogenesis, with temporal lesions situated at the junction between the frontonasal and maxillary facial prominences, and preauricular lesions at the meeting point of the maxillary and mandibular prominences. The ectodermal lesions show consistent histologic abnormalities: atrophy and flattening of the epidermis, replacement of the dermis by loose connective tissue, reduced levels of fragmented elastic tissue and absence of the subcutaneous tissues and adnexal structures. FFDD4 is characterized by isolated, preauricular skin lesions.
A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.
Glomerular basement membrane disease, nail-patella syndrome type
An autosomal dominant form of focal segmental glomerulosclerosis, a renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.
A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS6 is a childhood-onset disorder resulting in nephrotic syndrome, which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema.
Focal segmental glomerulosclerosis and neurodevelopmental syndrome
An autosomal dominant disorder characterized by global developmental delay associated with variable features of focal segmental glomerulosclerosis, a renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Some patients have transient proteinuria and others require renal transplant. Neurodevelopmental features are also variable, with some patients having only mildly impaired intellectual development, and others having a severe developmental disorder associated with early-onset refractory seizures or epileptic encephalopathy. Additional features, including feeding difficulties, poor overall growth, and non-specific dysmorphic facial features, are commonly observed.
Craniofacial dysostosis, hypertrichosis, hypoplasia of labia majora, dental and eye anomalies, patent ductus arteriosus, and normal intelligence
Progeroid syndrome, congenital, Petty type
An autosomal dominant progeroid disorder characterized by prenatal and postnatal growth retardation, decreased subcutaneous fat tissue, wrinkled skin, an aged appearance since birth, an abnormal scalp hair pattern, sparse hair, hypoplastic distal phalanges with hypoplastic nails, a widely open anterior fontanel, facial dysmorphisms, and craniosynostosis. Early death is observed in some patients.
Foveal hypoplasia and presenile cataract syndrome
Foveal hypoplasia with or without anterior segment anomalies and/or cataract
An isolated form of foveal hypoplasia, a developmental defect of the eye defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Clinical features include absence of foveal pit on optical coherence tomography, absence of foveal hyperpigmentation, absence of foveal avascularity, absence of foveal and macular reflexes, decreased visual acuity, and nystagmus. Anterior segment anomalies and cataract are observed in some FVH1 patients.
Foveal hypoplasia, optic nerve decussation defects, and anterior segment dysgenesis without albinism
Foveal hypoplasia and anterior segment dysgenesis
Foveal hypoplasia with or without optic nerve misrouting and/or anterior segment dysgenesis
An isolated form of foveal hypoplasia, a developmental defect of the eye defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Clinical features include absence of foveal pit on optical coherence tomography, absence of foveal hyperpigmentation, absence of foveal avascularity, absence of foveal and macular reflexes, decreased visual acuity, and nystagmus. Optic nerve misrouting and anterior segment dysgenesis are observed in some FVH2 patients.
An X-linked dominant disease characterized by moderate to severe intellectual disability, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most patients results from an amplification of a CGG repeat region in the FMR1 gene and abnormal methylation.
An X-linked neurodegenerative disorder characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive decline.
Autosomal recessive Melnick-Needles syndrome
A syndrome characterized by brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, full cheeks, small chin, bowing of the long bones and flexion deformity of the fingers.
A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities.
Characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant.
Friedreich ataxia with retained reflexes
Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region.
An X-linked disease characterized by generalized skeletal dysplasia, deafness, and urogenital defects.
A form of frontometaphyseal dysplasia, a progressive sclerosing skeletal dysplasia affecting the long bones and skull. Characteristic features include supraorbital hyperostosis, cranial hyperostosis, undermodeling of the small bones, flared metaphyses, and digital anomalies. Extra-skeletal manifestations include hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. FMD2 inheritance is autosomal dominant.
The term frontonasal dysplasia describes an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism; broadening of the nasal root; median facial cleft affecting the nose and/or upper lip and palate; unilateral or bilateral clefting of the alae nasi; lack of formation of the nasal tip; anterior cranium bifidum occultum; a V-shaped or widow's peak frontal hairline.
Disinhibition-dementia-parkinsonism-amyotrophy complex
Frontotemporal dementia-amyotrophic lateral sclerosis
Frontotemporal dementia and parkinsonism linked to chromosome 17
Frontotemporal dementia with parkinsonism
Frontotemporal lobar degeneration with TAU inclusions
Multiple system tauopathy with presenile dementia
A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. In some cases, parkinsonian symptoms are prominent. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, amygdala. In most cases, protein tau deposits are found in glial cells and/or neurons.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
Amyotrophic lateral sclerosis and/or frontotemporal dementia
Frontotemporal dementia and/or motor neuron disease
An autosomal dominant neurodegenerative disorder characterized by adult onset of frontotemporal dementia and/or amyotrophic lateral sclerosis in an affected individual. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 2
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 3
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Some FTDALS3 patients may also develop Paget disease of bone.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 4
Frontotemporal dementia and/or amyotrophic lateral sclerosis 5
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS5 is an autosomal dominant form with age-dependent penetrance. Penetrance is estimated to be 50% by age 56 and 100% by age 61.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 6
Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia (FTD) is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis (ALS) is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS6 is an autosomal dominant form characterized by onset of ALS or FTD in adulthood. Some patients with the disorder may have features of both diseases.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7
Amyotrophic lateral sclerosis, CHMP2B-related
Frontotemporal dementia, chromosome 3-linked
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia (FTD) is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis (ALS) is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS7 is an autosomal dominant form characterized by onset of ALS or FTD in adulthood. A few patients may have both phenotypes.
Frontotemporal dementia and/or amyotrophic lateral sclerosis 8
A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS8 is an autosomal dominant form.
An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, and episodes of hypoglycemia and metabolic acidosis that can be lethal in newborn infants or young children.
Benign defect of intermediary metabolism.
An autosomal recessive lysosomal storage disease characterized by accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Clinical signs include facial dysmorphism, dysostosis multiplex, moderate hepatomegaly, severe intellectual deficit, deafness, and according to age, angiokeratomas.
Hypoplasia femoral bowing and poly- syn- and oligodactyly
Distinct limb-malformation disorder characterized also by various degrees of limb aplasia/hypoplasia and joint dysplasia.
A severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy.
A form of fleck retina disease characterized by discrete uniform white dots over the entire fundus with greatest density in the mid-periphery and no macular involvement. Night blindness occurs. Inheritance can be autosomal dominant or autosomal recessive.
Autosomal recessive retinal disorder very similar to Stargardt disease. In contrast to Stargardt disease, FFM is characterized by later onset and slowly progressive course.
An enzymatic deficiency resulting in psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities.
An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development and intellectual disability. Most patients have behavioral and feeding problems, movement abnormalities, mild distal skeletal anomalies, and dysmorphic facial features.
Galactose-1-phosphate uridylyltransferase deficiency
A form of galactosemia, an inborn error of galactose metabolism typically manifesting in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. GALAC1 inheritance is autosomal recessive.
A form of galactosemia, an inborn error of galactose metabolism typically manifesting in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. GALAC2 inheritance is autosomal recessive.
A form of galactosemia, an inborn error of galactose metabolism typically manifesting in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. GALAC3 is an autosomal recessive form caused by galactose epimerase deficiency. It can manifest as benign, peripheral form with mild symptoms and enzymatic deficiency in circulating blood cells only. A second form, known as generalized epimerase deficiency, is characterized by undetectable levels of enzyme activity in all tissues and severe clinical features, including restricted growth and intellectual disability.
A form of galactosemia, an inborn error of galactose metabolism typically manifesting in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. GALAC4 inheritance is autosomal recessive.
Neuraminidase deficiency with beta-galactosidase deficiency
Protective protein cathepsin A deficiency
A lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, secondary to a defect in cathepsin A. All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and a normal or mildly affected mental state. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, intellectual disability, neurologic deterioration, absence of visceromegaly, and long survival.
One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes.
Microcephaly, hiatal hernia, and nephrotic syndrome
Nephrosis-neuronal dysmigration syndrome
Spinocerebellar ataxia, autosomal recessive, 5
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Patients may die in early childhood. GAMOS1 inheritance is autosomal recessive.
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS10 is an autosomal recessive form with fatal outcome. Patients manifest congenital hypothyroidism in addition to neurologic, renal and dysmorphic features.
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood.
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS6 is an autosomal recessive form with onset in infancy or early childhood. Affected individuals manifest microcephaly, global developmental delay, variable degrees of intellectual disability, and growth deficiency. Renal impairment may be age-dependent or may not be present.
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS7 inheritance is autosomal recessive.
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS8 inheritance is autosomal recessive.
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS9 inheritance is autosomal recessive.
An autosomal dominant syndrome characterized by global developmental delay with motor delay, moderate to severely impaired intellectual development, and poor speech acquisition in most patients. Additional features include hypotonia, feeding difficulties in infancy, and dysmorphic features. More variable features may include seizures, cardiac abnormalities, and non-specific findings on brain imaging.
Growth retardation, alopecia, pseudoanodontia, and optic atrophy
An autosomal recessive disease characterized by growth retardation, alopecia, failure of tooth eruption, and progressive optic atrophy in some patients.
Gastric adenocarcinoma and proximal polyposis of the stomach
Polyposis of gastric fundus without polyposis coli
A familial gastric polyposis syndrome characterized by autosomal dominant transmission of fundic gland polyposis with occasional hyperplastic and adenomatous polyps, sparing of the gastric antrum, and a significant risk of intestinal-type gastric adenocarcinoma development. Colorectal polyposis is not observed, and family history does not include colorectal cancer.
A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.
Gastrointestinal defects and immunodeficiency syndrome 1
Familial intestinal polyatresia syndrome
Gastrointestinal defects and immunodeficiency syndrome
Intestinal atresia, multiple and/or inflammatory bowel disease with or without immunodeficiency
Multiple intestinal atresia and/or inflammatory bowel disease with or without immunodeficiency
An autosomal recessive congenital disorder in which obstructions occur at various levels throughout the small and large intestines, ultimately leading to organ failure. Surgical interventions are palliative but do not provide long-term survival. Some patients exhibit inflammatory bowel disease (IBD), with or without intestinal atresia, and in some cases, the intestinal features are associated with either mild or severe combined immunodeficiency.
Gastrointestinal defects and immunodeficiency syndrome 2
Multiple intestinal atresia with or without leukopenia
A severe autosomal recessive disorder characterized by multiple intestinal atresia apparent soon after birth. Affected infants have a distended abdomen, bowel obstruction and do not pass meconium. There is some evidence of inflammatory bowel disease. Death occurs in the first weeks of life. Some patients may also have immunodeficiency.
Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery.
Gastrointestinal ulceration, recurrent, with dysfunctional platelets
Deficiency of phospholipase A2, group IVA
An autosomal recessive disorder characterized by recurrent gastrointestinal mucosal ulcers, gastrointestinal bleeding, chronic anemia, iron deficiency, and abdominal pain. Disease features also include platelet dysfunction, and globally decreased eicosanoid synthesis.
A lysosomal storage disease due to deficient activity of beta-glucocerebrosidase and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. Different clinical forms are recognized depending on the presence (neuronopathic forms) or absence of central nervous system involvement, severity and age of onset.
A form of Gaucher disease characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.
The most severe form of Gaucher disease. It manifests soon after birth, with death generally occurring before patients reach two years of age.
Cerebral, juvenile and adult, Gaucher disease
Gaucher disease chronic neuronopathic type
A subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease 2.
A variant of subacute neuronopathic Gaucher disease 3 associated with cardiovascular calcifications.
Distinct form of Gaucher disease type 2, characterized by fetal onset. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurologic involvement begins in the first week and leads to death within 3 months. Hepatosplenomegaly is a major sign, and is associated with ichthyosis, arthrogryposis, and facial dysmorphism.
Gaucher disease, atypical, due to saposin C deficiency
A disease characterized by marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease. Gaucher disease is a lysosomal storage disorder characterized by skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.
Gaze palsy, familial horizontal, with progressive scoliosis, 1
Familial horizontal gaze palsy with progressive scoliosis
An autosomal recessive neurologic disorder characterized by eye movement abnormalities apparent from birth, childhood-onset progressive scoliosis, distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.
Gaze palsy, familial horizontal, with progressive scoliosis, 2, with impaired intellectual development
An autosomal recessive neurologic disorder characterized by global developmental delay, delayed walking, intellectual disability, horizontal gaze palsy, and childhood-onset progressive scoliosis.
An autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues.
An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues.
A form of geleophysic dysplasia, a rare skeletal disease characterized by severe short stature, short hands and feet, and joint limitations. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include skin thickening, progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. GPHYSD3 inheritance is autosomal dominant.
Generalized epilepsy with febrile seizures plus 1
A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.
Generalized epilepsy with febrile seizures plus 10
Generalized epilepsy with febrile seizures plus, type 10
An autosomal dominant neurologic disorder with incomplete penetrance, characterized by variable types of seizures including absence, tonic-clonic, febrile, focal, and eyelid myoclonia. Some patients have normal neurologic development. Others have mild-to-moderate intellectual disability or autism spectrum disorder.
Generalized epilepsy with febrile seizures plus 2
Generalized epilepsy with febrile seizures plus 3
Generalized epilepsy with febrile seizures plus 5
Generalized epilepsy with febrile seizures plus 7
Generalized epilepsy with febrile seizures plus 9
Generalized epilepsy with febrile seizures plus, type 9
An autosomal dominant neurologic disorder characterized by febrile and/or afebrile seizures manifesting in early childhood. Seizure are variable and include generalized tonic-clonic, atonic, myoclonic, complex partial, and absence types. Most patients have remission of seizures later in childhood with no residual neurologic deficits. Rarely, patients may show mild developmental delay or mild intellectual disabilities.
A rare disorder consisting of microcephaly, severe psychomotor retardation, and characteristic coarse facial features, including broad nose and small or retracted chin, associated with congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies.
Genitourinary and/or brain malformation syndrome
An autosomal dominant syndrome characterized by multiple congenital anomalies including urogenital malformations and brain abnormalities ranging from agenesis of the corpus callosum to anencephaly.
A rare autosomal recessive disorder characterized by lax, wrinkled skin, joint laxity and a typical face with a prematurely aged appearance. Skeletal signs include severe osteoporosis leading to frequent fractures, malar and mandibular hypoplasia and a variable degree of growth retardation.
Cerebellar ataxia, progressive dementia, and amyloid deposits in CNS
Cerebral amyloidosis with spongiform encephalopathy
Subacute spongiform encephalopathy Gerstmann-Straussler type
A rare inherited prion disease characterized by adult onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain. GSD presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties, and the average disease duration is 7 years.
Rare autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Aregenerative anemia is characterized by bone marrow failure, so that functional marrow cells are regenerated slowly or not at all.
Giant axonal neuropathy 1, autosomal recessive
A severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. Axonal loss and the presence of giant axonal swellings filled with neurofilaments on nerve biopsies are the hallmarks of this neurodegenerative disorder.
Giant axonal neuropathy 2, autosomal dominant
HMSN2 with neurofilament accumulations and infrequent giant axons
An autosomal dominant peripheral axonal neuropathy characterized by onset of distal sensory impairment with lower extremity muscle weakness and atrophy after the second decade. Clinical features include foot deformities apparent in childhood, and cardiomyopathy in severely affected individuals. Sural nerve biopsy shows giant axonal swelling with neurofilament accumulation.
Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints.
Neurologic disorder manifested particularly by motor and vocal tics and associated with behavioral abnormalities.
Aniridia, cerebellar ataxia and mental deficiency
A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and intellectual disability.
Polycystic kidney disease, autosomal recessive, with microbrachycephaly, hypertelorism, and brachymelia
A rare autosomal recessive syndrome characterized by severe skeletal dysplasia, facial dysmorphic features, polycystic kidney disease and other visceral malformations. It may be lethal in utero or early in life. The skeletal features uniformly comprise a round pelvis, mesomelic shortening of the upper limbs and defective ossification of the cervical spine.
Gastrointestinal stromal tumor/GIST-plus syndrome
Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal
A disorder characterized by multiple mesenchymal tumors of the gastrointestinal tract, including gastrointestinal stromal tumor, inflammatory fibroid polyps, and fibroid tumors. Additional features are coarse facies and skin, broad hands and feet, and premature tooth loss. GISTPS is an autosomal dominant disease with incomplete penetrance. Gastrointestinal stromal tumor and inflammatory fibroid polyps may also occur in isolation.
Primary renotubular hypomagnesemia-hypokalemia with hypocalciuria
An autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. It has overlapping features with Bartter syndrome.
Deficiency of platelet fibrinogen receptor
Glycoprotein complex IIb-IIIa deficiency
Platelet glycoprotein IIb-IIIa deficiency
A form of Glanzmann thrombasthenia, a disorder characterized by failure of platelet aggregation, absent or diminished clot retraction, and mucocutaneous bleeding of mild-to-moderate severity. Glanzmann thrombasthenia has been classified into clinical types I and II. In type I, platelets show absence of glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express glycoprotein IIb-IIIa complexes at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. GT1 inheritance is autosomal recessive.
A form of Glanzmann thrombasthenia, a disorder characterized by failure of platelet aggregation, absent or diminished clot retraction, and mucocutaneous bleeding of mild-to-moderate severity. Glanzmann thrombasthenia has been classified into clinical types I and II. In type I, platelets show absence of glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express glycoprotein IIb-IIIa complexes at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability.
Juvenile-onset primary open angle glaucoma 1
A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.
A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. GLC1P is characterized by early onset, thin central corneas and low intraocular pressure.
Glaucoma, primary open angle, adult-onset
Glaucoma, primary open angle, juvenile-onset
Glaucoma 3A, primary open angle, congenital, juvenile, or adult onset
An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.
An autosomal dominant form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.
A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range.
An autosomal dominant form of primary glaucoma, an ocular disease characterized by a marked increase of intraocular pressure causing damage to eye structures and function. GLCC is characterized by elevated intraocular pressure due to iridocorneal angle closure with retention of the aqueous humor in the anterior chamber. Iridocorneal angle changes are apparent in the fourth to fifth decade of life, and patients manifest age-related variation in the severity of glaucomatous damage.
A complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes.
Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.
Global developmental delay with or without impaired intellectual development
An autosomal dominant disorder characterized by global developmental delay associated with mild-to-moderate intellectual disability, hypotonia and short stature in some patients.
Global developmental delay with speech and behavioral abnormalities
An autosomal dominant disorder manifesting in infancy or early childhood. It is characterized by mildly delayed fine and motor skills, mildly impaired intellectual development, speech and language delay, and variable behavioral abnormalities, mostly autism and attention-deficit hyperactivity disorder. Additional non-specific features include facial dysmorphism, myopia or strabismus, and skeletal defects.
Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies
An autosomal dominant syndrome characterized by underdevelopment of the corpus callosum, mild to moderate developmental delay and intellectual disability, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations.
Global developmental delay, lung cysts, overgrowth, and Wilms tumor
A disease characterized by the association of congenital nephromegaly, bilateral Wilms tumor, somatic overgrowth, developmental delay, macrocephaly, and bilateral lung cysts.
Global developmental delay, progressive ataxia, and elevated glutamine
Glutaminase deficiency with impaired intellectual development and progressive ataxia
An autosomal recessive disease characterized by early-onset delay in motor skills, delayed speech, progressive ataxia, and neurologic deterioration. Plasma glutamine is persistently elevated by a factor of 2.5 despite normal plasma ammonia levels.
Glomerulopathy with fibronectin deposits 2
Familial glomerular nephritis with fibronectin deposits
Genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life.
Characterized by the presence of smooth-muscle-like glomus cells in the media surrounding distended vascular lumens.
Hereditary unresponsiveness to adrenocorticotropic hormone
A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.
Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency
Hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.
Cortisol resistance from glucocorticoid receptor defect
An autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of Cushing syndrome typical signs. Clinical features include hypoglycemia, hypertension, metabolic alkalosis, chronic fatigue and profound anxiety.
Blood-brain barrier glucose transport defect
GLUT1 deficiency syndrome autosomal recessive
A neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe intellectual disability.
Paroxysmal exercise-induced dystonia with or without epilepsy and/or hemolytic anemia
Paroxysmal exertion-induced dyskinesia with or without epilepsy and/or hemolytic anemia
PED with or without epilepsy and/or hemolytic anemia
A clinically variable disorder characterized primarily by onset in childhood of paroxysmal exercise-induced dyskinesia. The dyskinesia involves transient abnormal involuntary movements, such as dystonia and choreoathetosis, induced by exercise or exertion, and affecting the exercised limbs. Some patients may also have epilepsy, most commonly childhood absence epilepsy. Mild intellectual disability may also occur. In some patients involuntary exertion-induced dystonic, choreoathetotic, and ballistic movements may be associated with macrocytic hemolytic anemia.
Glutamate formiminotransferase deficiency
Autosomal recessive disorder. Features of a severe phenotype, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and intellectual disability. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities.
An autosomal recessive metabolic disorder characterized by progressive dystonia and athetosis due to gliosis and neuronal loss in the basal ganglia.
Multiple acyl-CoA dehydrogenase deficiency
An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
A metabolic disorder due to peroxisomal glutaryl-CoA oxidase deficiency and characterized by the excretion of abnormal quantities of glutaric acid but low 3-hydroxyglutaric acid.
Severe form characterized by an increased rate of hemolysis and defective function of the central nervous system.
Glutathione synthetase deficiency of erythrocytes
A very rare, autosomal recessive metabolic disorder characterized by the presence of glutathione in the urine, due to generalized gamma-glutamyl transpeptidase deficiency. Most patients manifest mild to moderate intellectual disability, and behavioral disturbance. Seizures, tremor, marfanoid features and strabismus are observed in some patients.
A metabolic disorder manifesting as 3 clinically distinct forms: infantile, juvenile, and adult. The infantile form is the most severe and is associated with severe developmental delay and adrenal insufficiency. Patients with the adult form have no symptoms and are often detected fortuitously. GKD results in hyperglycerolemia, a condition characterized by the accumulation of glycerol in the blood and urine.
Glycine encephalopathy with normal serum glycine
An autosomal recessive, severe metabolic disorder characterized by arthrogryposis multiplex congenita, joint hyperlaxity, lack of neonatal respiratory effort, axial hypotonia, hypertonia with pronounced clonus, and delayed psychomotor development. Some patients may have dysmorphic facial features and/or brain imaging abnormalities. Laboratory studies show increased CSF glycine and normal or only mildly increased serum glycine. Most patients die in infancy.
The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases.
Hypoglycemia with deficiency of glycogen synthetase in the liver
A metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood, high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia.
Muscle phosphoglycerate mutase deficiency
Myopathy due to phosphoglycerate mutase deficiency
A metabolic disorder characterized by myoglobinuria, increased serum creatine kinase levels, decreased phosphoglycerate mutase activity, myalgia, muscle pain, muscle cramps, exercise intolerance.
A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.
A metabolic disorder associated with increased hepatic glycogen and hemolytic anemia. It may lead to myopathy with exercise intolerance and rhabdomyolysis.
A metabolic disorder that results in exercise-induced myalgias, generalized muscle weakness and fatigability. It is characterized by increased serum creatine kinase and decreased enolase 3 activity. Dramatically reduced protein levels with focal sarcoplasmic accumulation of glycogen-beta particles are detected on ultrastructural analysis.
A metabolic disorder resulting in muscle weakness, associated with the glycogen depletion in skeletal muscle, and cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart. The skeletal muscle shows a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation.
Hepatorenal form of glycogen storage disease
A metabolic disorder characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Patients manifest a wide range of clinical symptoms and biochemical abnormalities, including hypoglycemia, severe hepatomegaly due to excessive accumulation of glycogen, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia.
A metabolic disorder characterized by impairment of terminal steps of glycogenolysis and gluconeogenesis. Patients manifest a wide range of clinical symptoms and biochemical abnormalities, including hypoglycemia, severe hepatomegaly due to excessive accumulation of glycogen, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia, and hyperuricemia. Glycogen storage disease type 1B patients also present a tendency towards infections associated with neutropenia, relapsing aphthous gingivostomatitis, and inflammatory bowel disease.
A metabolic disorder with a broad clinical spectrum. The severe infantile form, or Pompe disease, presents at birth with massive accumulation of glycogen in muscle, heart and liver. Cardiomyopathy and muscular hypotonia are the cardinal features of this form whose life expectancy is less than two years. The juvenile and adult forms present as limb-girdle muscular dystrophy beginning in the lower limbs. Final outcome depends on respiratory muscle failure. Patients with the adult form can be free of clinical symptoms for most of their life but finally develop a slowly progressive myopathy.
A metabolic disorder associated with an accumulation of abnormal glycogen with short outer chains. It is clinically characterized by hepatomegaly, hypoglycemia, short stature, and variable myopathy. Glycogen storage disease type 3 includes different forms: GSD type 3A patients lack glycogen debrancher enzyme activity in both liver and muscle, while GSD type 3B patients are enzyme-deficient in liver only. In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in GSD type 3C or type 3D, respectively.
A metabolic disorder characterized by the accumulation of an amylopectin-like polysaccharide. The typical clinical manifestation is liver disease of childhood, progressing to lethal hepatic cirrhosis. Most children with this condition die before two years of age. However, the liver disease is not always progressive. No treatment apart from liver transplantation has been found to prevent progression of the disease. There is also a neuromuscular form of glycogen storage disease type 4 that varies in onset (perinatal, congenital, juvenile, or adult) and severity.
A metabolic disorder resulting in myopathy characterized by exercise intolerance, cramps, muscle weakness and recurrent myoglobinuria.
A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.
A metabolic disorder characterized by exercise intolerance with associated nausea and vomiting, muscle cramping, exertional myopathy and compensated hemolysis. Short bursts of intense activity are particularly difficult. Severe muscle cramps and myoglobinuria develop after vigorous exercise.
A metabolic disorder resulting in a mild liver glycogenosis with clinical symptoms that include hepatomegaly, growth retardation, muscle weakness, elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting hyperketosis. Two subtypes are known: type 1 or classic type with no phosphorylase kinase activity in liver or erythrocytes, and type 2 or variant type with no phosphorylase kinase activity in liver, but normal activity in erythrocytes. Unlike other glycogenosis diseases, glycogen storage disease type 9A is generally a benign condition. Patients improve with age and are often asymptomatic as adults. Accurate diagnosis is therefore also of prognostic interest.
Phosphorylase kinase deficiency of liver and muscle
A metabolic disorder characterized by hepatomegaly, only slightly elevated transaminases and plasma lipids, clinical improvement with increasing age, and remarkably no clinical muscle involvement. Biochemical observations suggest that this mild phenotype is caused by an incomplete holoenzyme that lacks the beta subunit, but that may possess residual activity.
A metabolic disorder manifesting in infancy with hepatomegaly, growth retardation, hypotonia, liver dysfunction, and elevated plasma aminotransferases and lipids. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis.
A metabolic disorder characterized by slowly progressive, predominantly distal muscle weakness and atrophy. Clinical features include exercise intolerance with early fatigability, pain, cramps and occasionally myoglobinuria.
Glycogen storage disease of heart lethal congenital
Congenital nonlysosomal cardiac glycogenosis
Phosphorylase kinase deficiency of heart
Rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise.
Glycosylphosphatidylinositol biosynthesis defect 1
An autosomal recessive disorder characterized by portal vein thrombosis and portal hypertension, absence seizures, macrocephaly, splenomegaly, cytopenias and early-onset cerebral infarctions.
Glycosylphosphatidylinositol biosynthesis defect 11
An autosomal recessive neurologic disorder characterized by developmental delay, intellectual disability, tonic seizures associated with hypsarrhythmia, dysmorphic facial features, and elevated serum alkaline phosphatase.
Glycosylphosphatidylinositol biosynthesis defect 15
Developmental delay, epilepsy, cerebellar atrophy, and osteopenia
An autosomal recessive disorder characterized by delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most patients, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria.
Glycosylphosphatidylinositol biosynthesis defect 16
An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, and seizures.
Glycosylphosphatidylinositol biosynthesis defect 17
An autosomal recessive disorder characterized by variable neurologic deficits that become apparent in infancy or early childhood. Clinical features include learning disabilities, mild-to-moderate developmental delay, seizures of variable severity, aggressive or over-friendly behavior, and autistic features.
Glycosylphosphatidylinositol biosynthesis defect 18
An autosomal recessive disorder with onset in utero or early infancy and characterized by severe global developmental delay, seizures, hypotonia, weakness, ataxia, and dysmorphic facial features.
Glycosylphosphatidylinositol biosynthesis defect 25
Neurodevelopmental disorder with hypotonia and contractures
An autosomal recessive disorder with onset in early infancy and characterized by global developmental delay with almost no milestone achievement, brain anomalies, hypotonia, and contractures. Death may occur in early childhood.
Gangliosidosis generalized GM1 infantile type
An autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1-gangliosidosis type 1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life.
Gangliosidosis generalized GM1 late infantile type
GM1-gangliosidosis generalized juvenile type
A gangliosidosis characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose-terminal oligosaccharides. Inheritance is autosomal recessive.
Gangliosidosis generalized GM1 chronic type
GM1-gangliosidosis generalized adult type
A gangliosidosis with a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive.
An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the absence of HEXA activity, leading to neurodegeneration and, in the infantile form, death in early childhood. It exists in several forms: infantile (most common and most severe), juvenile and adult (late-onset).
An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. Clinically indistinguishable from GM2-gangliosidosis type 1, presenting startle reactions, early blindness, progressive motor and mental deterioration, macrocephaly and cherry-red spots on the macula.
An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the presence of both normal hexosaminidase A and B.
This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and intellectual disability. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms.
Osteogenesis imperfecta with unusual skeletal lesions
Rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. Patients experience frequent bone fractures caused by trivial accidents in childhood; however the fractures heal normally without bone deformity. The jaw lesions replace the tooth-bearing segments of the maxilla and mandible with fibrous connective tissues, including various amounts of cementum-like calcified mass, sometimes causing facial deformities. Patients also have a propensity for jaw infection and often suffer from purulent osteomyelitis-like symptoms, such as swelling of and pus discharge from the gums, mobility of the teeth, insufficient healing after tooth extraction and exposure of the lesions into the oral cavity.
Goiter multinodular 1, with or without Sertoli-Leydig cell tumors
Goiter nontoxic with intrathyroidal calcification
Goiter non-toxic with intrathyroidal calcification
A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary.
A disorder characterized by intellectual disability, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease.
Cerebellar ataxia and hypogonadotropic hypogonadism
Deficiency of luteinizing hormone-releasing hormone with ataxia
A disease characterized by cerebellar symptoms and signs of sex steroid deficiency. Clinical features include cerebellar and brain stem atrophy, cerebellar ataxia, hypothalamic LHRH deficiency, hypogonadotrophic hypogonadism, lack of secondary sexual characteristics, and infertility.
Lethal skeletal dysplasia with gracile bones
A perinatally lethal condition characterized by narrowing of the medullary cavity of the long bones and of the skull, gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia. Most affected individuals who survive beyond the perinatal period develop hypocalcemia with low parathyroid hormone levels.
GRACILE stands for 'growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death'. It is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism.
Arterial occlusive disease, progressive, with hypertension, heart defects, bone fragility, and brachysyndactyly
An autosomal recessive syndrome of stenosis or occlusion of multiple arteries, including renal, abdominal, cerebral and probably coronary arteries, congenital heart defects, brachydactyly, syndactyly, bone fragility, and learning disabilities.
Granulomatous disease, chronic, autosomal recessive, 1
Chronic granulomatous disease autosomal recessive cytochrome b-positive type I
Chronic granulomatous disease due to NCF1 deficiency
Deficiency of neutrophil cytosol factor 1
A form of chronic granulomatous disease, a primary immunodeficiency characterized by severe recurrent bacterial and fungal infections, along with manifestations of chronic granulomatous inflammation. It results from an impaired ability of phagocytes to mount a burst of reactive oxygen species in response to pathogens.
Granulomatous disease, chronic, autosomal recessive, 2
Chronic granulomatous disease autosomal recessive cytochrome b-positive type II
Deficiency of neutrophil cytosol factor 2
Granulomatous disease, chronic, autosomal recessive, 3
CGD autosomal recessive cytochrome b-positive type III
Chronic granulomatous disease autosomal recessive cytochrome b-positive type III
Granulomatous disease chronic due to NCF4 deficiency
Granulomatous disease, chronic, autosomal recessive, 4
CGD due to deficiency of alpha subunit of cytochrome b
Chronic granulomatous disease autosomal recessive cytochrome b-negative
Granulomatous disease, chronic, cytochrome-b-negative, autosomal recessive
Granulomatous disease, chronic, autosomal recessive, 5
Granulomatous disease, chronic, due to CYBC1 deficiency
A form of chronic granulomatous disease, a primary immunodeficiency characterized by severe recurrent bacterial and fungal infections, along with manifestations of chronic granulomatous inflammation. It results from an impaired ability of phagocytes to mount a burst of reactive oxygen species in response to pathogens. CGD5 is an autosomal recessive form characterized by onset of recurrent infections and severe colitis in the first decade of life. Clinical manifestations include increased susceptibility to catalase-positive organisms, features of inflammatory bowel disease, lymphopenia, lymphadenitis, and autoinflammatory symptoms in some patients.
Granulomatous disease, chronic, X-linked
Chronic granulomatous disease cytochrome b-negative X-linked
Chronic granulomatous disease cytochrome b-positive X-linked
A rare platelet disorder characterized by a selective deficiency in the number and contents of platelet alpha-granules. It is associated with mild to moderate bleeding tendency and moderate thrombocytopenia. The platelets are enlarged and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules.
Chondrodystrophy, hydropic and prenatally lethal type
Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
A rare autosomal recessive chondrodystrophy characterized by early in utero lethality. Affected fetuses typically present with fetal hydrops, short-limbed dwarfism, and a marked disorganization of chondro-osseous calcification, and ectopic ossification centers.
Autosomal dominant disorder affecting limb and craniofacial development. It is characterized by pre- and postaxial polydactyly, syndactyly of fingers and toes, macrocephaly and hypertelorism.
Griscelli syndrome with primary neurologic impairment
Rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, silvery-gray hair and accumulation of melanosomes in melanocytes. GS1 patients show developmental delay, hypotonia and intellectual disability, without apparent immune abnormalities.
Rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. GS2 patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome, known as hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation. Neurological impairment is present in some patients, likely as a result of hemophagocytic syndrome.
Rare autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes, without other clinical manifestations.
Growth hormone deficiency with pituitary anomalies
A disease characterized by low or absent growth hormone levels, in the presence of a hypoplastic anterior pituitary lobe and ectopic or absent posterior pituitary lobe.
Growth hormone deficiency, isolated partial
A disorder characterized by partial growth hormone deficiency resulting in growth delay and short stature, sometimes associated with recurrent episodes of abdominal pain, vomiting, ketosis and hypoglycemia.
Growth hormone deficiency isolated autosomal recessive
Isolated growth hormone deficiency type IA
An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone.
Isolated growth hormone deficiency type IB
An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy.
Growth hormone deficiency isolated autosomal dominant
Isolated growth hormone deficiency type II
Pituitary dwarfism due to isolated growth hormone deficiency autosomal dominant
An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.
Growth hormone deficiency, isolated, 3, with agammaglobulinemia
Agammaglobulinemia and isolated growth hormone deficiency
Isolated growth hormone deficiency, type III, with agammaglobulinemia
Isolated growth hormone deficiency type 3
X-linked hypogammaglobulinemia and isolated growth hormone deficiency
An X-linked recessive disorder characterized by growth hormone deficiency, short stature, delayed bone age, agammaglobulinemia with markedly reduced numbers of B cells, and good response to treatment with growth hormone.
Growth hormone deficiency, isolated, type IV
Isolated growth hormone deficiency, type IV
An autosomal recessive deficiency of growth hormone leading to early and severe growth failure and short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy.
Growth hormone insensitivity syndrome with immune dysregulation 1, autosomal recessive
Growth hormone insensitivity due to postreceptor defect
Laron syndrome due to a post-receptor defect
An autosomal recessive form of growth hormone insensitivity syndrome, a congenital disease characterized by short stature, growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, resistance to exogeneous growth hormone therapy, and recurrent infections. Most, but not all, patients have features of immune dysregulation.
Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant
An autosomal dominant form of growth hormone insensitivity syndrome, a congenital disease characterized by short stature, growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, resistance to exogeneous growth hormone therapy, and recurrent infections. GHISID2 patients usually have delayed bone age, delayed puberty, and decreased serum IGF1. Some patients may have features of mild immune dysregulation, such as eczema, increased serum IgE, asthma, or celiac disease.
Isolated partial growth hormone deficiency
A disease characterized by partial resistance to growth hormone resulting in short stature. Short stature is defined by a standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for sex and chronological age, compared with a well-nourished, healthy, genetically relevant population.
Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies
An autosomal recessive disorder characterized by pre- and postnatal growth restriction with microcephaly, distinctive craniofacial features, congenital alopecia, hypoplastic kidneys with renal insufficiency, global developmental delay, severe congenital sensorineural hearing loss, hydrocephalus, genital hypoplasia, and early mortality.
Growth retardation, developmental delay, and facial dysmorphism
Growth retardation developmental delay coarse facies early death
Lethal polymalformative syndrome Boissel type
A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.
Growth retardation, impaired intellectual development, hypotonia, and hepatopathy
An autosomal recessive disorder characterized by severe growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and hepatic dysfunction.
Dominantly inherited combination of distal limb and genital tract abnormalities. It has several features in common with hand-foot-genital syndrome, including hypoplastic first digits and hypospadias. Typical features not seen in hand-foot-genital syndrome include postaxial polydactyly of the hands and uniphalangeal second toes with absent nails.
Autosomal dominant disorder characterized by persistent blisters and suprabasal cell separation (acantholysis) of the epidermis, due to impaired keratinocyte adhesion. Patients lacking all isoforms except isoform 2 have HHD.
Keratosis palmoplantaris with periodontopathia and onychogryposis
An autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis.
Acroosteolysis with osteoporosis and changes in skull and mandible
Serpentine Fibula-Polycystic Kidney Syndrome
A rare, autosomal dominant skeletal disorder characterized by the association of facial anomalies, acro-osteolysis, general osteoporosis, insufficient ossification of the skull, and periodontal disease (premature loss of permanent teeth). Other features include cleft palate, congenital heart defects, polycystic kidneys, orthopedic problems and anomalies of the genitalia, intestines and eyes.
A disorder characterized by a typical skull shape (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin atrophy, dental anomalies and proportionate short stature. Intellectual disability is present in a minority of cases.
Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies
An autosomal recessive, congenital neurodevelopmental disorder characterized by intrauterine growth retardation, microcephaly, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness, optic nerve atrophy with no eye fixation, and death in early childhood. Brain imaging shows semilobar holoprosencephaly and agenesis of corpus callosum.
A syndrome characterized by severe hypertelorism, upslanting palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Additional features include myopia, mild to moderate sensorineural hearing loss, gonadal anomalies and borderline intelligence.
A disorder characterized by limb and genitourinary anomalies. Clinical features include small feet with unusually short great toes and abnormal thumbs. Females with the disorder have duplication of the genital tract.
Intellectual developmental disorder with impaired speech, behavioral abnormalities, and dysmorphic facies
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, varying degrees of intellectual disability, autism spectrum disorder, poor or absent speech, and mild facial dysmorphism. Most patients develop seizures. Additional variable features include hypotonia, hypogonadism in males, and ocular anomalies.
An autosomal recessive form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. HARPO is a rare erythropoietic variant form characterized by neonatal hemolytic anemia, sometimes accompanied by skin lesions, and massive excretion of harderoporphyrin in feces.
Cholestasis with pigmentary retinopathy and cleft palate syndrome
An X-linked dominant, multiple congenital anomaly syndrome characterized by foregut malformations, intestinal malrotation, liver and biliary tract disease, genitourinary abnormalities, facial clefting, and pigmentary retinopathy. Some patients may have congenital cardiac defects or vascular abnormalities, including aortic coarctation and carotid/intracranial aneurysms. Neurodevelopment and cognition is normal.
A syndrome characterized by global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. Some patients have optic atrophy and hypertrophic cardiomyopathy. HAYOS inheritance can be autosomal dominant or autosomal recessive.
Autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport noted for its clinical variability. First described in 1956, HND is characterized by increases in the urinary and intestinal excretion of neutral amino acids. Individuals with typical Hartnup aminoaciduria may be asymptomatic, some develop a photosensitive pellagra-like rash, attacks of cerebellar ataxia and other neurological or psychiatric features. Although the definition of HND was originally based on clinical and biochemical abnormalities, its marked clinical heterogeneity has led to it being known as a disorder with a consistent pathognomonic neutral hyperaminoaciduria.
Holoprosencephaly, ectrodactyly and bilateral cleft lip/palate
A syndrome characterized by the triad of holoprosencephaly, ectrodactyly, and cleft/lip palate. Profound intellectual disability is also present. Multiple other congenital anomalies usually occur.
4-alpha-hydroxyphenylpyruvate hydroxylase deficiency
4-hydroxyphenylpyruvic acid dioxygenase deficiency
An inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine.
17-beta-hydroxysteroid dehydrogenase X deficiency
2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency
3-hydroxyacyl-CoA dehydrogenase II deficiency
3-hydroxyacyl-CoA dehydrogenase type 2 deficiency
3-hydroxyacyl-CoA dehydrogenase type-2 deficiency
3-hydroxyacyl-CoA dehydrogenase type II deficiency
An X-linked multisystemic disorder with highly variable severity. Age at onset ranges from the neonatal period to early childhood. Features include progressive neurodegeneration, psychomotor retardation, loss of mental and motor skills, seizures, cardiomyopathy, and visual and hearing impairment. Some patients manifest lactic acidosis and metabolic acidosis.
Neurodevelopmental disorder with heart and brain malformations
An autosomal recessive syndrome characterized by multiple congenital anomalies such as cardiac defects, brain malformations, including cerebellar vermis hypoplasia, hypoplastic corpus callosum and Dandy-Walker malformation, profoundly delayed psychomotor development, microphthalmia, and facial dysmorphism.
Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations.
Hearing loss, sensorineural, with enamel hypoplasia and nail defects
Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities
A form of Heimler syndrome, a very mild peroxisome biogenesis disorder characterized by sensorineural hearing loss, amelogenesis imperfecta resulting in enamel hyoplasia of the secondary dentition, nail defects, and occasional or late-onset retinal pigmentation abnormalities.
Form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency.
Hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia
An autosomal recessive disease characterized by congenital heat intolerance, generalized anhidrosis, inability to produce tears, dry mouth, electrolyte imbalance, and ichthyosis.
A disorder characterized by intellectual disability, autism spectrum disorder, and dysmorphic facial features including prominent forehead, high hairline, downslanting palpebral fissures, notched eyelids, broad nasal bridge, thin upper lip, and smooth philtrum.
A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring.
An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane.
A disease characterized by impaired stress hematopoiesis, resulting in marked erythrocyte fragmentation and intravascular hemolysis, coagulation abnormalities, endothelial damage, and iron deposition in renal and hepatic tissues. Clinical features include persistent hemolytic anemia, asplenia, nephritis, generalized erythematous rash, growth retardation and hepatomegaly.
A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.
A juvenile form of hemochromatosis, a disorder of iron metabolism with excess deposition of iron in a variety of organs leading to their failure, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of juvenile hemochromatosis at presentation are hypogonadism and cardiomyopathy.
Hemochromatosis due to defect in transferrin receptor 2
Hemochromatosis due to defect in ferroportin
A form of alpha-thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence.
Hemolytic anemia due to adenylate kinase deficiency
A disease characterized by hemolytic anemia and undetectable erythrocyte adenylate kinase activity.
Hemolytic anemia due to elevated adenosine deaminase
Hemolytic anemia due to elevated erythrocyte ADA
Hemolytic anemia due to erythrocyte adenosine deaminase overproduction
An X-linked disorder characterized by onset of mild to moderate red cell anemia soon after birth or in childhood. The anemia is associated with significantly increased adenosine deaminase activity, specifically in erythrocyte precursors.
Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency
A disease characterized by hemolytic anemia, glutathione deficiency, myopathy, late-onset spinocerebellar degeneration, and peripheral neuropathy.
Hemolytic anemia due to glutathione reductase deficiency
An autosomal recessive disease characterized by hemolytic anemia and impaired activity of glutathione reductase. Patients experience hemolytic anemia in response to oxidative stress or ingestion of fava beans.
Hemolytic anemia, CD59-mediated, with or without polyneuropathy
CD59-mediated hemolytic anemia with or without immune-mediated polyneuropathy
An autosomal recessive disorder characterized by infantile onset of chronic hemolysis and a relapsing-remitting polyneuropathy, often exacerbated by infection, and manifested as hypotonia, limb muscle weakness, and hyporeflexia.
An X-linked hematologic disease characterized by shortened survival of erythrocytes due to congenital hemolysis that cannot be compensated by bone marrow activity. Clinical features are mild jaundice and anemia. Red cells morphology is normal.
Hemolytic anemia, non-spherocytic, due to glucose phosphate isomerase deficiency
A form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency.
Hemolytic disease of fetus and newborn, RH-induced
A disease that occurs in pregnancies in which mothers who lack the D antigen (RhD) of the Rh blood group have been exposed to the RhD-positive red cells of the fetus. The resulting maternal autoantibodies cross the placenta and destroy fetal red cells.
Atypical hemolytic uremic syndrome with H factor anomaly
Hemolytic-uremic syndrome without diarrhea
An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.
Atypical hemolytic uremic with MCP or CD46 anomaly
Atypical hemolytic uremic syndrome with I factor anomaly
Atypical hemolytic uremic syndrome with B factor anomaly
Atypical hemolytic uremic syndrome with C3 anomaly
Atypical hemolytic uremic syndrome with thrombomodulin anomaly
An atypical form of hemolytic uremic syndrome characterized by acute onset in the first year of life of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. After the acute episode, most patients develop chronic renal insufficiency. Unlike other genetic forms of aHUS, AHUS7 is not related to abnormal activation of the complement system.
Hemophagocytic lymphohistiocytosis, familial, 2
A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia.
Hemophagocytic lymphohistiocytosis, familial, 3
Hemophagocytic lymphohistiocytosis, familial, 4
Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease
A rare, autosomal recessive disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. Some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease.
A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery.
Plasma thromboplastin component deficiency
An X-linked blood coagulation disorder characterized by a permanent tendency to hemorrhage, due to factor IX deficiency. It is phenotypically similar to hemophilia A, but patients present with fewer symptoms. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma.
Hemorrhagic destruction of the brain with subependymal calcification and cataracts
A syndrome characterized by congenital cataracts and severe brain abnormalities apparently resulting from hemorrhagic destruction of the brain parenchyma, including the cerebral white matter and basal ganglia. Patients manifest profound developmental delay, and other neurologic features included seizures, spasticity, and hyperreflexia. The clinical course is very severe resulting in death in infancy. Brain imaging shows multifocal intraparenchymal hemorrhage with associated liquefaction and massive cystic degeneration, and calcification in the subependymal region and in brain tissue.
Neurodevelopmental disorder with spasticity, facial dysmorphism, and brain abnormalities
An autosomal recessive disorder characterized by severe global developmental delay apparent from infancy or early childhood. Affected individuals have delayed walking or inability to walk, impaired intellectual development with poor or absent speech, lower limb spasticity, poor overall growth, and dysmorphic facial features. Some patients develop seizures. Brain imaging shows thinning of the posterior part of the corpus callosum, delayed myelination, and cerebral and cerebellar atrophy.
Hennekam lymphangiectasia-lymphedema syndrome 1
A form of Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and some manifest intellectual disability. HKLLS1 inheritance is autosomal recessive.
Hennekam lymphangiectasia-lymphedema syndrome 2
A form of Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and some manifest intellectual disability. HKLLS2 individuals have lymphangiectasia variably affecting the gut, pericardium, lungs, kidneys, and genitalia. Other features include camptodactyly and rare syndactyly. HKLLS2 inheritance is autosomal recessive.
Hennekam lymphangiectasia-lymphedema syndrome 3
A form of Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and some manifest intellectual disability. HKLLS3 is characterized by widespread congenital edema, facial dysmorphism and protein-losing enteropathy of variable severity. HKLLS3 transmission pattern is consistent with autosomal recessive inheritance.
Rare benign liver tumors of presumable epithelial origin that develop in an otherwise normal liver. Hepatic adenomas may be single or multiple. They consist of sheets of well-differentiated hepatocytes that contain fat and glycogen and can produce bile. Bile ducts or portal areas are absent. Kupffer cells, if present, are reduced in number and are non-functional. Conditions associated with adenomas are insulin-dependent diabetes mellitus and glycogen storage diseases (types 1 and 3).
A disorder characterized by elevated levels of beta-migrating very low density lipoproteins, and abnormally triglyceride-rich low and high density lipoproteins.
Hepatic venoocclusive disease with immunodeficiency
Autosomal recessive primary immunodeficiency associated with hepatic vascular occlusion and fibrosis. The immunodeficiency is characterized by severe hypogammaglobulinemia, combined T and B-cell immunodeficiency, absent lymph node germinal centers, and absent tissue plasma cells.
An autosomal recessive form of fulminant viral hepatitis, a disease that strikes otherwise healthy individuals during primary infection with common liver-tropic viruses. FVH is characterized by severe liver destruction in the absence of a preexisting liver disorder, leading to encephalopathy within 8 weeks of the onset of the first symptoms.
A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. HEP is a cutaneous porphyria that presents in infancy. It is characterized biochemically by excessive excretion of acetate-substituted porphyrins and accumulation of protoporphyrin in erythrocytes. Uroporphyrinogen decarboxylase levels are very low in erythrocytes and cultured skin fibroblasts.
An autosomal recessive disorder characterized by progressive degenerative liver fibrosis, fibrocystic kidney disease, and hypertrophic cardiomyopathy with atypical fibrotic patterns on histopathology. Disease onset is variable, ranging from childhood to adulthood.
Hereditary angiopathy with nephropathy aneurysms and muscle cramps
The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries.
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Hereditary coproporphyria is an acute hepatic porphyria characterized by skin photosensitivity, attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. Hereditary coproporphyria is biochemically characterized by overexcretion of coproporphyrin III in the urine and in the feces.
Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or intellectual disability become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent.
Autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life.
Hereditary hypophosphatemic rickets with hypercalciuria
Autosomal recessive form of hypophosphatemia characterized by reduced renal phosphate reabsorption and rickets. Increased serum levels of 1,25-dihydroxyvitamin D lead to increase in urinary calcium excretion.
Autosomal recessive disorder characterized by megaloblastic anemia.
Hereditary leiomyomatosis and renal cell cancer
Leiomyomatosis and renal cell cancer hereditary
Multiple cutaneous and uterine leiomyomata
Multiple cutaneous and uterine leiomyomata 1 with or without renal cell carcinoma
A disorder characterized by predisposition to cutaneous and uterine leiomyomas, and papillary type 2 renal cancer which occurs in about 20% of patients.
EXT is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3 respectively. EXT is a dominantly inherited skeletal disorder primarily affecting endochondral bone during growth. The disease is characterized by formation of numerous cartilage-capped, benign bone tumors (osteocartilaginous exostoses or osteochondromas) that are often accompanied by skeletal deformities and short stature. In a small percentage of cases exostoses have exhibited malignant transformation resulting in an osteosarcoma or chondrosarcoma. Osteochondromas development can also occur as a sporadic event.
Hereditary neuralgic amyotrophy with predilection for brachial plexus
Autosomal dominant form of recurrent focal neuropathy characterized clinically by acute, recurrent episodes of brachial plexus neuropathy with muscle weakness and atrophy preceded by severe pain in the affected arm. HNA is triggered by environmental factors such as infection or parturition.
Hereditary neuropathy with liability to pressure palsies
A neurologic disorder characterized by transient episodes of decreased perception or peripheral nerve palsies after slight traction, compression or minor traumas.
A form of lifelong, persistent neutrophilia, a condition characterized by an increase in the number of neutrophils in the blood.
Hereditary non-polyposis colorectal cancer 6
An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.
Hereditary non-polyposis colorectal cancer 7
Autosomal recessive hematologic disorder characterized by hemolytic anemia, microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells.
Hereditary susceptibility to Wilms tumor 5
Pediatric malignancy of kidney and one of the most common solid cancers in childhood.
Albinism with hemorrhagic diathesis and pigmented reticuloendothelial
A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. HPS10 patients manifest albinism, neutropenia, immunodeficiency, neurodevelopmental delay, generalized seizures, and impaired hearing.
A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. HPS2 differs from the other forms of HPS in that it includes immunodeficiency in its phenotype and patients with HPS2 have an increased susceptibility to infections.
Dextrocardia with other cardiac malformations
Situs inversus with complex cardiac defects and splenic defects X-linked
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations.
Heterotaxy, visceral, 10, autosomal, with male infertility
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX10 is an autosomal recessive form associated with male infertility.
Heterotaxy, visceral, 11, autosomal, with male infertility
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX11 is an autosomal recessive form associated with male infertility due to reduced flagellar motility.
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. Early death may occur. HTX12 inheritance is autosomal recessive.
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX4 clinical features include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.
An autosomal dominant form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX5 clinical features include situs inversus viscerum or situs ambiguus, congenital heart defect, transposition of the great vessels ventricular septal defect, atrial septal defect, truncus communis, and dextrocardia.
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX6 clinical features are situs inversus totalis and severe complex cardiac malformations including unbalanced atrioventricular canal defects, transposition of the great arteries with severe pulmonary stenosis, right aortic arch, abnormal systemic venous return and total anomalous pulmonary venous drainage.
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX7 inheritance is autosomal recessive.
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX8 inheritance is autosomal recessive.
Heterotaxy, visceral, 9, autosomal, with male infertility
A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX9 is an autosomal recessive form associated with male infertility, mainly due to defective sperm motility.
Rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature.
Microcephaly, short stature, and impaired intellectual development
An autosomal dominant form of microcephalic dwarfism. Affected individuals have intrauterine growth retardation, postnatal growth restrictions, proportionate short stature, microcephaly, severe developmental delay and impaired intellectual development. More variable features include sparse hair, short broad metacarpals and phalanges, and mild recurrent infections.
Hiatt-Neu-Cooper neurodevelopmental syndrome
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, delayed walking or inability to walk, impaired intellectual development, poor or absent speech, axial hypotonia, and facial dysmorphism. Additional variable features may include seizures, autistic or behavioral abnormalities, and brain abnormalities.
Rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings.
High molecular weight kininogen deficiency
Autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis.
A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.
Hirschsprung disease, cardiac defects, and autonomic dysfunction
A disorder characterized by skip-lesions Hirschsprung disease, craniofacial abnormalities and other dysmorphic features, cardiac defects including ductus arteriosus, small subaortic ventricular septal defect, small atrial septal defect, and autonomic dysfunction.
Autosomal recessive disease characterized by increased histidine and histamine as well as decreased urocanic acid in body fluids.
Histiocytosis-lymphadenopathy plus syndrome
Cutaneous hyperpigmentation with hypertrichosis hepatosplenomegaly heart anomalies and hypogonadism with or without hearing loss
Histiocytosis and lymphadenopathy with or without cutaneous cardiac and/or endocrine features joint contractures and/or deafness
Histiocytosis with joint contractures and sensorineural deafness
Pigmented hypertrichosis with insulin-dependent diabetes mellitus
Sinus histiocytosis and massive lymphadenopathy
A syndrome characterized by the combination of features from 2 or more of four histiocytic disorders, originally thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC features include joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes. SHML causes lymph node enlargement in children frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. H syndrome is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss is found in about half of patients. PHID is characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome.
Biotin-responsive multiple carboxylase deficiency
Early-onset multiple carboxylase deficiency
A neonatal form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. In holocarboxylase synthetase deficiency, clinical and biochemical symptoms improve dramatically with administration of biotin.
A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.
Holoprosencephaly 12 with or without pancreatic agenesis
An autosomal dominant form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. HPE12 clinical features include abnormal forebrain development, dysmorphic features, global developmental delay, learning difficulties, and congenital absence of the pancreas in most patients, resulting in early-onset insulin-dependent diabetes mellitus. Other features may include hearing loss and absence of the gallbladder.
An X-linked form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. HPE13 features range from full alobar holoprosencephaly with cyclopia to semilobar holoprosencephaly or septooptic dysplasia. Dysmorphic features include microcephaly, hypotelorism, low-set ears, micrognathia, and cleft lip/palate. Patients with a more severe phenotype may die in the newborn period, whereas those with a less severe phenotype show global developmental delay.
An autosomal recessive form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. In its most severe form (alobar holoprosencephaly), the forebrain consists of a single ventricle, and midbrain structures may be malformed as well. In the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. In milder forms (semilobar or lobar holoprosencephaly), rudimentary midline structures are present. The less severe form features facial dysmorphism characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum.
A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of holoprosencephaly type 3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described.
Pituitary anomalies with holoprosencephaly-like features
A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Holoprosencephaly type 9 is characterized by defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia.
Developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects.
Homocystinuria due to deficiency of N(5,10)-methylenetetrahydrofolate reductase activity
Methylenetetrahydrofolate reductase deficiency
An autosomal recessive inborn error of folate metabolism. Clinical severity is variable, ranging from severe neurologic features to absence of symptoms. Clinical features include homocysteinuria, homocysteinemia, developmental delay, severe intellectual disability, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders.
Homocystinuria-megaloblastic anemia, cblE complementation type
Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism cblE complementation type
Vitamin B12-responsive homocystinuria cblE type
An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent.
Homocystinuria-megaloblastic anemia, cblG complementation type
Homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism cblG complementation type
An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia.
Prenatal growth retardation with progressive pancytopenia and cerebellar hypoplasia
A clinically severe variant of dyskeratosis congenita that is characterized by multisystem involvement, early onset in utero, and often results in death in childhood. Affected individuals show intrauterine growth retardation, microcephaly, cerebellar hypoplasia, delayed development, and bone marrow failure resulting in immunodeficiency.
Humerofemoral hypoplasia with radiotibial ray deficiency
A severe disease characterized by reduction of all four limbs as well as hypoplasia of the upper limb girdle and pelvis. Rudimentary finger- or toe-like appendages may be present. HHRRD transmission pattern is consistent with autosomal recessive inheritance.
A neurodegenerative disorder characterized by involuntary movements (chorea), general motor impairment, psychiatric disorders and dementia. Onset of the disease occurs usually in the third or fourth decade of life. Onset and clinical course depend on the degree of poly-Gln repeat expansion, longer expansions resulting in earlier onset and more severe clinical manifestations. Neuropathology of Huntington disease displays a distinctive pattern with loss of neurons, especially in the caudate and putamen.
Autosomal dominant, early-onset neurodegenerative disorder with prominent psychiatric features.
Huntington disease (HD) is a neurodegenerative disorder resulting primarily from the loss of medium spiny projection neurons in the striatum, especially in the caudate nucleus, and, to a lesser extent, atrophy of mesencephalic and cortical structures. The typical clinical picture of HD combines familial adult onset chorea and subcortical dementia that usually begin during the fourth decade of life.
Keratoderma with scleroatrophy of the extremities
Scleroatrophic and keratotic dermatosis of limbs
An autosomal dominant syndrome characterized by atrophic fibrosis of the skin of the limbs, nail hypoplasia, and palmoplantar keratoderma. Malignant degeneration of affected skin resulting in aggressive squamous cell carcinoma and early metastasis formation is a distinctive feature of the syndrome.
A rare type of thyroid cancer accounting for only about 3-10% of all differentiated thyroid cancers. These neoplasms are considered a variant of follicular carcinoma of the thyroid and are referred to as follicular carcinoma, oxyphilic type.
Rare genetic disorder characterized by features reminiscent of marked premature aging.
An autosomal recessive syndrome characterized by abnormal growth of hyalinized fibrous tissue usually affecting subcutaneous regions on the scalp, ears, neck, face, hands, and feet. The lesions appear as pearly papules or fleshy nodules. Additional features include gingival hypertrophy, progressive joint contractures resulting in severe limitation of mobility, osteopenia, and osteoporosis. Disease severity is variable. Some individuals manifest symptoms in infancy and have additional visceral or systemic involvement. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to early death. Surviving children may suffer from severely reduced mobility due to joint contractures. Other patients have later onset of a milder disorder affecting only the face and digits.
A disorder characterized by excessive trophoblast development that produces a growing mass of tissue inside the uterus at the beginning of a pregnancy. It leads to abnormal pregnancies with no embryo, and cystic degeneration of the chorionic villi.
Hydrocephalus due to stenosis of the aqueduct of Sylvius
Hydrocephalus is a condition in which abnormal accumulation of cerebrospinal fluid in the brain causes increased intracranial pressure inside the skull. This is usually due to blockage of cerebrospinal fluid outflow in the brain ventricles or in the subarachnoid space at the base of the brain. In children is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions. In adults the syndrome includes incontinence, imbalance, and dementia. HSAS is characterized by intellectual disability and enlarged brain ventricles.
Hydrocephalus, congenital communicating, 1
A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. Affected individuals may have neurologic impairment. HYDCC1 inheritance is autosomal dominant.
Hydrocephalus, non-syndromic, autosomal recessive 1
A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. Affected individuals may have neurologic impairment. HYC1 inheritance is autosomal recessive.
Hydrocephalus, congenital, 2, with or without brain or eye anomalies
Hydrocephalus, non-syndromic, autosomal recessive 2
A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. HYC2 affected individuals have variable neurologic impairment. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and non-specific dysmorphic features, may be observed. HYC2 inheritance is autosomal recessive.
Hydrocephalus, congenital, 3, with brain anomalies
Hydrocephalus, non-syndromic, autosomal recessive 3
A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. HYC3 features include enlarged ventricles, hypoplastic or absent cerebellum, holoprosencephaly and Dandy-Walker malformation. Most patients die in utero or shortly after birth. HYC3 inheritance is autosomal recessive.
An autosomal dominant neurologic disorder characterized by a slowly progressive gait disorder, urinary incontinence, progressive intellectual decline, and ventricular enlargement on brain imaging. Cerebrospinal fluid pressure tends to be in the high normal range.
A lethal syndrome characterized by polydactyly, central nervous system malformation, and hydrocephalus. The polydactyly is postaxial in the hands and preaxial in the feet. A highly characteristic hallux duplex is seen in almost no other situation. In half of the cases, a large atrioventricular communis defect of the heart is found. The pregnancy is characterized by hydramnios, which is often massive, and by preterm delivery.
An embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Duplication of the hallux is a common finding.
Hydrops, lactic acidosis, and sideroblastic anemia
A lethal, multisystem metabolic disorder characterized by severe lactic acidosis, hydrops, and sideroblastic anemia. Additional features include impaired cardiac function, disordered coagulation, pulmonary hypertension, and progressive renal disease.
An inborn error of amino acid metabolism characterized by massive urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid. Affected individuals manifest renal tubular dysfunction, metabolic acidosis, psychomotor retardation, non-progressive encephalopathy, and muscular hypertonia.
Hyper-IgE recurrent infection syndrome 1, autosomal dominant
Hyper-IgE recurrent infection syndrome autosomal dominant
A rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures.
Hyper-IgE recurrent infection syndrome 2, autosomal recessive
Hyper-IgE recurrent infection syndrome autosomal recessive
A rare disorder characterized by immunodeficiency, recurrent infections, eczema, increased serum IgE, eosinophilia and lack of connective tissue and skeletal involvement.
Hyper-IgE recurrent infection syndrome 3, autosomal recessive
An immunologic disorder characterized by skin bacterial infections in particular with Staphylococcus aureus, susceptibility to fungal infections such as chronic mucocutaneous candidiasis, atopic dermatitis, recurrent respiratory infections, bronchiectasis, and increased serum IgE and IgG. Immunologic work-up shows impaired differentiation of CD4+ T cells into T-helper 17 cells, decreased memory B cells, and often decreased NK cells. Some patients manifest extrahemapoietic features, including facial dysmorphism, abnormal dentition, alopecia, joint hypermobility and bone fractures. Disease onset is in early childhood.
Hyper-IgE recurrent infection syndrome 4A, autosomal dominant
An immunologic disorder characterized by recurrent mainly sino-pulmonary infections associated with increased serum IgE. Some patients have onset of symptoms in early childhood and develop complications, including bronchiectasis or hemoptysis, whereas others have later onset of less severe infections. Immunologic workup usually shows normal leukocyte levels, although some patients may demonstrate alterations in lymphocyte subsets, including T cells. Affected individuals also have variable skeletal abnormalities, including high-arched palate, hyperextensible joints, scoliosis, and bone fractures.
Hyper-IgE recurrent infection syndrome 4B, autosomal recessive
An immunologic disorder characterized by recurrent infections, mainly affecting the respiratory tract, skin and eye, and skeletal abnormalities including craniosynostosis and scoliosis. Immunologic workup shows increased serum IgE, intermittent eosinophilia, impaired development of certain B- and T-cell populations, as well as impaired acute-phase response. Disease onset is in early childhood.
Hyper-IgE recurrent infection syndrome 5, autosomal recessive
An immunologic disorder characterized by recurrent sinopulmonary and deep skin infections, mostly caused by bacteria, including H. influenza and Staphylococcus aureus. Additional features include asthma, atopic dermatitis, and impaired inflammatory responses during infection. Disease onset is in early infancy.
ACTH-dependent hyperaldosteronism syndrome
Aldosteronism sensitive to dexamethasone
Glucocorticoid-suppressible hyperaldosteronism
A disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol. There is significant phenotypic heterogeneity, and some individuals never develop hypertension.
An autosomal dominant disorder characterized by elevated plasma aldosterone level and hypertension of varying severity even within members of the same family. Hypokalemia is observed in some patients. In HALD2, hypertension does not improve with glucocorticoid treatment.
A form of hyperaldosteronism characterized by hypertension secondary to massive adrenal mineralocorticoid production. HALD3 patients present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. Hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension.
A form of familial hyperaldosteronism, a disorder characterized by hypertension, elevated aldosterone levels despite low plasma renin activity, and abnormal adrenal steroid production. There is significant phenotypic heterogeneity, and some individuals never develop hypertension.
Cholesteryl ester transfer protein deficiency
A condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels.
Hyperammonemia due to carbonic anhydrase VA deficiency
An autosomal recessive inborn error of metabolism, clinically characterized by infantile hyperammonemic encephalopathy. Metabolic abnormalities include hypoglycemia, hyperlactatemia, metabolic acidosis and respiratory alkalosis.
An autosomal recessive form of primary conjugated hyperbilirubinemia. Affected individuals develop mild jaundice not associated with hemolysis shortly after birth or in childhood. They have delayed plasma clearance of the unconjugated anionic dye bromsulphthalein and prominent urinary excretion of coproporphyrin I. Hepatic pigmentation is normal.
A condition characterized by a green discoloration of the skin, urine, serum, and other bodily fluids. It is due to increased biliverdin resulting from inefficient conversion to bilirubin. Affected individuals appear to have symptoms only in the context of obstructive cholestasis and/or liver failure. In some cases, green jaundice can resolve after resolution of obstructive cholestasis.
A disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis.
An autosomal recessive form of hypercalcemia, a disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis.
A common type of hypercalciuria, a condition characterized by excessive urinary calcium excretion. Absorptive hypercalciuria is due to gastrointestinal hyperabsorption of calcium and is a frequent cause of calcium oxalate nephrolithiasis.
Hypercarotenemia and vitamin A deficiency, autosomal dominant
A disorder characterized by increased serum beta-carotene, decreased conversion of beta-carotene to vitamin A and decreased serum vitamin A.
An autosomal recessive disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.
A disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption.
An autosomal recessive inborn error of metabolism characterized by persistently increased plasma levels of conjugated bile salts apparent from infancy, fat malabsorption and impaired absorption of fat-soluble vitamins, including D and K. Most patients are asymptomatic. Some neonates may have transient jaundice or transiently elevated liver enzymes.
Hypercholesterolemic xanthomatosis, familial
A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL1 inheritance is autosomal dominant.
Familial ligand-defective apolipoprotein B-100
A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL2 inheritance is autosomal dominant.
Hypercholesterolemia, autosomal dominant, 3
A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL3 inheritance is autosomal dominant.
Autosomal recessive hypercholesterolemia 1
Autosomal recessive hypercholesterolemia 2
Hypercholesterolemia, autosomal recessive
A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL4 inheritance is autosomal recessive.
Characterized by persistent elevated levels of serum creatine kinase without muscle weakness.
Hyperekplexia hereditary 1 autosomal dominant or recessive
A neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli.
A neurologic disorder characterized by neonatal hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes. Notably, in some cases, symptoms resolved in the first year of life.
An autosomal recessive severe neurologic disorder apparent from birth. HKPX4 is characterized by little if any development, hypertonia, early-onset refractory seizures in some patients, and respiratory failure resulting in early death, mostly in the first months of life.
Hyperferritinemia with or without cataract
Hyperferritinemia, hereditary, with congenital cataracts
An autosomal dominant disease characterized by elevated level of ferritin in serum and tissues, and early-onset bilateral cataract. Cataracts may be subclinical in some patients.
Hyperglycinemia, lactic acidosis, and seizures
Pyruvate dehydrogenase lipoic acid synthetase deficiency
An enzymatic defect resulting in an autosomal recessive disorder of mitochondrial metabolism. It is characterized by early-onset lactic acidosis, severe encephalomyopathy, and a pyruvate oxidation defect. Affected individuals have neonatal-onset epilepsy, poor growth, psychomotor retardation, muscular hypotonia, lactic acidosis, and elevated glycine concentration in plasma and urine.
Glycinuria with or without oxalate nephrolithiasis
Glycinuria with or without oxalate urolithiasis
A condition characterized by excess of glycine in the urine. In some cases it is associated with renal colic and renal oxalate stones.
Hyperimmunoglobulinemia D and periodic fever syndrome
Autosomal recessive disease characterized by recurrent episodes of unexplained high fever associated with skin rash, diarrhea, adenopathy (swollen, tender lymph nodes), arthralgias and/or arthritis. Concentration of IgD, and often IgA, are above normal.
Hyperinsulinemic hypoglycemia, familial, 8
A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF8 is an autosomal recessive form characterized by episodes of symptomatic hypoglycemia provoked by protein feeding, and persistent mild hyperammonemia. Affected children tend to have recurrent generalized seizures.
A disorder characterized by a variable pattern of elevated levels of serum total cholesterol, triglycerides or both. It is observed in a percentage of individuals with premature coronary heart disease.
A disorder characterized by a variable pattern of elevated levels of serum total cholesterol, triglycerides or both. It is observed in a percentage of individuals with premature coronary heart disease. FCHL3 inheritance is autosomal dominant.
Hyperlipemia, idiopathic, Burger-Grutz type
An autosomal recessive metabolic disorder characterized by defective breakdown of dietary fats, impaired clearance of chylomicrons from plasma causing the plasma to have a milky appearance, and severe hypertriglyceridemia. On a normal diet, patients often present with abdominal pain, hepatosplenomegaly, lipemia retinalis, eruptive xanthomata, and massive hypertriglyceridemia, sometimes complicated with acute pancreatitis.
Autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis.
An autosomal recessive disorder characterized by hyperlipoproteinemia, decreased plasma LPL levels in some patients, high plasma triglyceride levels, and refractory fasting chylomicronemia.
Deficiency or defect of apolipoprotein E
Dysbetalipoproteinemia due to defect in apolipoprotein E
Familial hyperbeta- and prebetalipoproteinemia
Familial hypercholesterolemia with hyperlipemia
Hyperlipemia with familial hypercholesterolemic xanthomatosis
A disorder characterized by the accumulation of intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features include xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause.
Characterized by increased amounts of chylomicrons and very low density lipoprotein (VLDL) and decreased low density lipoprotein (LDL) and high density lipoprotein (HDL) in the plasma after a fast. Numerous conditions cause this phenotype, including insulin-dependent diabetes mellitus, contraceptive steroids, alcohol abuse, and glycogen storage disease type 1A (GSD1A).
Alpha-aminoadipic semialdehyde synthase deficiency
Lysine:alpha-ketoglutarate reductase deficiency
An autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant.
Hypermanganesemia with dystonia, polycythemia, and cirrhosis
A metabolic autosomal recessive disorder characterized by dystonia, parkinsonism, extrapyramidal signs, severe hypermanganesemia, polycythemia, and chronic hepatic disease, including steatosis and cirrhosis.
A metabolic autosomal recessive disorder characterized by increased blood manganese levels, neurodegeneration, and rapidly progressive parkinsonism and dystonia. Affected individuals present with loss of developmental milestones, progressive dystonia and bulbar dysfunction in infancy or early childhood. Towards the end of the first decade, they manifest severe generalized pharmacoresistant dystonia, spasticity, limb contractures and scoliosis, and loss of independent ambulation. Cognition may be impaired, but is better preserved than motor function.
Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2
A disorder apparent in infancy and characterized by euthyroid hypermetabolism, failure to thrive despite excessive caloric intake, intermittent hyperthermia, and developmental delay.
Hypermethioninemia due to adenosine kinase deficiency
A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.
Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency
A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.
Hyperornithinemia with gyrate atrophy of choroid and retina
Ornithine-delta-aminotransferase deficiency
Ornithine keto acid aminotransferase deficiency
A disorder clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence.
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
An autosomal recessive disorder of the urea cycle characterized by onset in early life. The acute phase of the disease is characterized by vomiting, ataxia, lethargy, confusion, and coma. Chronic clinical manifestations include hypotonia, developmental delay, progressive encephalopathy with mental regression, and spastic paraparesis with pyramidal signs.
An autosomal dominant bone disorder characterized by endosteal hyperostosis and osteosclerosis of the calvaria and the skull base. The progressive bone overgrowth causes entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII, its first symptoms often presenting during the second decade of life.
Alanine-glyoxylate aminotransferase deficiency
Peroxisomal alanine glyoxylate aminotransferase deficiency
Serine pyruvate aminotransferase deficiency
An inborn error of glyoxylate metabolism characterized by increased excretion of oxalate and glycolate, and progressive tissue accumulation of insoluble calcium oxalate. Affected individuals are at risk for nephrolithiasis, nephrocalcinosis and early onset end-stage renal disease.
Glyoxylate reductase/hydroxypyruvate reductase deficiency
A disorder characterized by elevated urinary excretion of oxalate and L-glycerate, progressive tissue accumulation of insoluble calcium oxalate, nephrolithiasis, nephrocalcinosis, and end-stage renal disease.
A disorder phenotypically similar to hyperoxaluria type 1 and type 2. It is characterized by increase in urinary oxalate excretion and mild glycolic aciduria. Clinical manifestations include calcium oxalate urolithiasis, hematuria, pain, and/or urinary tract infection.
Hyperparathyroidism, familial, isolated, primary
An autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid hyperplasia, adenomas, and carcinomas.
Familial primary hyperparathyroidism with multiple ossifying jaw fibromas
An autosomal dominant neoplasia syndrome characterized by primary hyperparathyroidism, ossifying fibroma of the maxilla and/or mandible, renal tumor, and uterine tumors. It is associated with increased risk of parathyroid cancer.
A form of familial primary hyperparathyroidism, a hypercalcemic disorder caused by inappropriate oversecretion of parathyroid hormone due to parathyroid hyperplasia or neoplasms. Clinical features include hypercalcemia, phosphaturia, and increased bone resorption. HRPT4 inheritance is autosomal dominant.
Neonatal severe primary hyperparathyroidism
A disorder characterized by severe hypercalcemia, bone demineralization, and failure to thrive usually manifesting in the first 6 months of life. If untreated, NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy.
An autosomal recessive disease characterized by impaired transplacental maternal-fetal transport of calcium, high serum PTH levels and signs of metabolic bone disease in the neonatal period. Skeletal anomalies include generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. Affected individuals experience postnatal respiratory and feeding difficulties. The condition improves within a short time after birth once calcium is provided orally.
Mildest form of phenylalanine hydroxylase deficiency.
6-pyruvoyl-tetrahydropterin synthase deficiency
Hyperphenylalaninemia tetrahydrobiopterin-deficient due to PTS deficiency
An autosomal recessive disorder characterized by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits. Neurological symptoms are unresponsive to the classic phenylalanine-low diet.
Atypical severe phenylketonuria due to GTP cyclohydrolase I deficiency
Guanosine triphosphate cyclohydrolase I deficiency
Hyperphenylalaninemia with neopterin deficiency
A disease characterized by malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency, and defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia. In this intermediate phenotype, there is marked motor delay, but no intellectual disability and only minimal, if any, hyperphenylalaninemia.
Hyperphenylalaninemia tetrahydrobiopterin-deficient due to DHPR deficiency
Quinoid dihydropteridine reductase deficiency
Rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. Patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated.
Hyperphenylalaninemia tetrahydrobiopterin-deficient due to PHS deficiency
Hyperphenylalaninemia tetrahydrobiopterin-deficient due to pterin-4-alpha-carbinolamine dehydratase deficiency
Hyperphenylalaninemia with primapterinuria
Pterin-4-alpha-carbinolamine dehydratase deficiency
An autosomal recessive disease characterized by primapterinuria, a variant form of hyperphenylalaninemia defined by increased excretion of 7-substituted pterins in the urine. Patients with primapterinuria show an increased ratio of neopterin to biopterin in the urine, excretion of subnormal levels of biopterins, and normal levels of biogenic amines in cerebrospinal fluid. Neurologic signs are mild, present in the neonatal period only, and include hypotonia, delayed motor development and tremor.
Hyperphenylalaninemia, mild, non-BH4-deficient
An autosomal recessive disorder characterized by increased serum phenylalanine, normal BH4 metabolism, and highly variable neurologic defects, including movement abnormalities and intellectual disability.
Hyperphosphatasia with impaired intellectual development syndrome 1
Glycosylphosphatidylinositol biosynthesis defect 2
A severe syndrome characterized by elevated serum alkaline phosphatase, severe intellectual disability, seizures, hypotonia, facial dysmorphism, and hypoplastic terminal phalanges.
Hyperphosphatasia with impaired intellectual development syndrome 2
Glycosylphosphatidylinositol biosynthesis defect 6
An autosomal recessive form of intellectual disability characterized by facial dysmorphism, brachytelephalangy, and persistent elevated serum alkaline phosphatase (hyperphosphatasia). Some patients may have additional features, such as cardiac septal defects or seizures.
Hyperphosphatasia with impaired intellectual development syndrome 3
Glycosylphosphatidylinositol biosynthesis defect 8
An autosomal recessive disorder usually characterized by intellectual disability, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase.
Hyperphosphatasia with impaired intellectual development syndrome 4
Glycosylphosphatidylinositol biosynthesis defect 10
An autosomal recessive neurologic disorder characterized by profound developmental delay, severe intellectual disability, no speech, psychomotor delay, postnatal microcephaly, and elevated serum alkaline phosphatase.
Hyperphosphatasia with impaired intellectual development syndrome 6
An autosomal recessive, multisystem disorder characterized by severe developmental delay, dysmorphism, seizures, cataracts, and early death in some patients.
Hyperpigmentation with or without hypopigmentation, familial progressive
A disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age. Hyperpigmentation has variable intensity, and sometimes is associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules.
An autosomal dominant condition characterized by elevated levels of serum proinsulin-like material.
A disorder characterized by increased levels of prolactin in the blood not associated with gestation or the puerperium. HPRL may result in infertility, hypogonadism, and galactorrhea.
An inborn error of proline metabolism resulting in elevated levels of proline in the plasma and urine. The disorder is generally benign and most affected individuals are clinically asymptomatic. Some patients, however, have neurologic manifestations, including epilepsy and intellectual disability. Association with certain forms of schizophrenia have been reported.
1-pyrroline-5-carboxylate dehydrogenase deficiency
An inborn error of proline metabolism resulting in elevated plasma levels of proline and delta-1-pyrroline-5-carboxylate (P5C). The condition is considered to be benign, but affected individuals can exhibit neurological manifestations that vary in severity. Clinical signs include seizures, intellectual deficit and mild developmental delay.
Brachydactyly, type E, with short stature and hypertension
Brachydactyly type E with short stature and hypertension
A syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals.
Familial hyperthyroidism due to mutations in TSH receptor
Hyperthyroidism congenital non-autoimmune
Hyperthyroidism non-autoimmune autosomal dominant
Resistance to thyroid stimulating hormone
Toxic thyroid hyperplasia autosomal dominant
A condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent.
Dystransthyretinemic euthyroidal hyperthyroxinemia
A condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.
Hyperthyroxinemia, familial dysalbuminemic
A disorder characterized by abnormally elevated levels of total serum thyroxine (T4) in euthyroid patients. It is due to abnormal serum albumin that binds T4 with enhanced affinity.
A rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability.
A common inherited disorder in which the concentration of very low density lipoprotein (VLDL) is elevated in the plasma. This leads to increased risk of heart disease, obesity, and pancreatitis. Inheritance is autosomal dominant.
An autosomal dominant form of hypertriglyceridemia, a disorder characterized by elevated plasma triglyceride levels. HYTG2 patients also have increased total cholesterol levels and low levels of high density lipoprotein (HDL) cholesterol. Reduced penetrance has been observed.
Hypertriglyceridemia, transient infantile
An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis.
Hypertrophic osteoarthropathy, primary, autosomal dominant
A form of primary hypertrophic osteoarthropathy, a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. PHOAD patients may also experience joint swelling and pain, and some have reported gastrointestinal symptoms, including watery diarrhea. Males are more commonly affected, and more severely affected, than females.
Hypertrophic osteoarthropathy, primary, autosomal recessive, 1
Pachydermoperiostosis autosomal recessive
A disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease.
Hypertrophic osteoarthropathy, primary, autosomal recessive, 2
An autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia.
An X-linked metabolic disorder characterized by uric acid excess in the blood, renal stones, uric acid nephropathy, and renal obstruction. After puberty, the hyperuricemia may cause gout.
Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome
A multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely.
Hypervalinemia and hyperleucine-isoleucinemia
Branched-chain aminotransferase deficiency
Hypervalinemia or hyperleucine-isoleucinemia
An autosomal recessive metabolic disorder characterized by highly elevated plasma concentrations of valine and leucine/isoleucine. Affected individuals suffer from headache and mild memory impairment.
An autosomal dominant disorder characterized by decreased plasma high density lipoproteins, moderately low HDL cholesterol, a reduction in cellular cholesterol efflux, and susceptibility to premature coronary artery disease.
Hypoalphalipoproteinemia, primary, 2, autosomal recessive
An autosomal recessive disorder of lipoprotein metabolism, biochemically characterized by severe apoA-I deficiency and severely reduced serum high-density lipoprotein cholesterol (HDL-C). Affected individuals have undetectable serum levels of apoA-I, and develop xanthomas and corneal opacities. The disease is generally associated with atherosclerosis and markedly increased cardiovascular risk.
Hypoalphalipoproteinemia, primary, 2, intermediate
Hypoalphalipoproteinemia, primary, 2, autosomal dominant
An autosomal dominant disorder of lipoprotein metabolism, biochemically characterized by partial apoA-I deficiency and reduced serum high-density lipoprotein cholesterol (HDL-C). Affected individuals have half the normal plasma apoA-I and HDL-C levels, and may develop xanthomas and corneal opacities. Most patients do not have increased cardiovascular risk.
Acanthocytosis with hypobetalipoproteinemia
Normotriglyceridemic hypobetalipoproteinemia
A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Clinical presentation may vary from no symptoms to severe gastrointestinal and neurological dysfunction similar to abetalipoproteinemia.
Combined hypobetalipoproteinemia familial
A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Affected individuals present with combined hypolipidemia, consisting of extremely low plasma levels of LDL cholesterol, HDL cholesterol, and triglycerides.
Autosomal dominant hypocalcemia with Bartter syndrome
A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia.
A form of hypocalcemia, a disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications.
Familial benign hypocalciuric hypercalcemia 1
A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.
Familial benign hypercalcemia Oklahoma type
Familial benign hypocalciuric hypercalcemia 3
Autosomal dominant disease and is characterized by disproportionate short stature. It resembles achondroplasia, but with a less severe phenotype.
Hypogonadotropic hypogonadism 1 with or without anosmia
Dysplasia olfactogenitalis of De Morsier
Hypogonadotropic hypogonadism and anosmia
A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Hypogonadotropic hypogonadism 10 with or without anosmia
Hypogonadotropic hypogonadism 11 with or without anosmia
Hypogonadotropic hypogonadism 12 with or without anosmia
Gonadotropin deficiency, familial idiopathic
Hypogonadotropic hypogonadism 13 with or without anosmia
Hypogonadotropic hypogonadism 14 with or without anosmia
Hypogonadotropic hypogonadism 15 with or without anosmia
Hypogonadotropic hypogonadism 16 with or without anosmia
Hypogonadotropic hypogonadism 17 with or without anosmia
Hypogonadotropic hypogonadism 18 with or without anosmia
Hypogonadotropic hypogonadism 19 with or without anosmia
Hypogonadotropic hypogonadism 2 with or without anosmia
Hypogonadotropic hypogonadism 20 with or without anosmia
Hypogonadotropic hypogonadism 21 with or without anosmia
Hypogonadotropic hypogonadism 22 with or without anosmia
Hypogonadotropic hypogonadism 23 with or without anosmia
A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. HH23 male patients have normal sexual differentiation, reduced or absent Leydig cells, reduced or absent spermatogenesis, and absence of spontaneous puberty. Female patients exhibit normal pubertal development and menarche, followed by oligomenorrhea and anovulatory secondary amenorrhea.
Hypogonadotropic hypogonadism 24 with or without anosmia
Follicle-stimulating hormone deficiency, isolated
A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. HH24 is characterized by primary amenorrhea in women, oligo or azoospermia with low to normal testosterone levels in men, and infertility.
Hypogonadotropic hypogonadism 25 with anosmia
A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH25 is an autosomal dominant form with anosmia, characterized by intrafamilial variable expressivity and incomplete penetrance.
Hypogonadotropic hypogonadism 26 with or without anosmia
A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH26 is characterized by micropenis and cryptorchidism at birth in male patients, and absent puberty and anosmia in male or female patients. Some affected individuals also exhibit craniosynostosis. Inheritance can be autosomal dominant or autosomal recessive.
Hypogonadotropic hypogonadism 27 without anosmia
A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH27 is an autosomal recessive normosmic form characterized by lack of pubertal development associated with onset of obesity in early adolescence.
Hypogonadotropic hypogonadism 3 with or without anosmia
Hypogonadotropic hypogonadism 4 with or without anosmia
Hypogonadotropic hypogonadism 5 with or without anosmia
Hypogonadotropic hypogonadism 6 with or without anosmia
Hypogonadotropic hypogonadism 7 with or without anosmia
Congenital hypogonadotropic hypogonadism normosmic
Idiopathic hypogonadotropic hypogonadism
Hypogonadotropic hypogonadism 8 with or without anosmia
Hypogonadotropic hypogonadism 9 with or without anosmia
Hypoinsulinemic hypoglycemia with hemihypertrophy
A disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures.
An autosomal recessive disease characterized by renal tubulopathy with hypokalemia, salt wasting, disturbed acid-base homeostasis, and sensorineural deafness.
Hypomagnesemia with secondary hypocalcemia
Intestinal hypomagnesemia with secondary hypocalcemia
A disorder due to a primary defect in intestinal magnesium absorption. It is characterized by low levels of serum magnesium alongside with a normal renal magnesium secretion, secondary hypocalcemia and calcinocis. Affected individuals show neurologic symptoms of hypomagnesemic hypocalcemia, including seizures and muscle spasms, during infancy. Hypocalcemia is secondary to parathyroid failure resulting from magnesium deficiency. Untreated, the disorder may be fatal or may result in neurological damage.
A disorder due to primary renal wasting of magnesium. Plasma levels of other electrolytes are normal. The only abnormality found, in addition to low magnesium levels, is lowered renal excretion of calcium resulting in hypocalciuria.
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis
Renal hypomagnesemia hypercalciuria nephrocalcinosis
A progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis. Recurrent urinary tract infections and kidney stones are often observed. In spite of hypercalciuria, patients do not show hypocalcemia.
A disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to moderate psychomotor retardation, and brisk tendon reflexes.
Hypomagnesemia 5, renal, with or without ocular involvement
Familial hypomagnesemia with hypercalciuria, nephrocalcinosis and severe ocular involvement
Hypomagnesemia 5 renal with ocular involvement
Hypomagnesemia renal with ocular involvement
Macular coloboma bilateral with hypercalciuria
A progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. The renal phenotype is virtually undistinguishable from that of patients with HOMG3.
A renal disease characterized by severely lowered serum magnesium levels in the absence of other electrolyte disturbances. Affected individuals show an inappropriately normal urinary magnesium excretion, demonstrating a defect in tubular reabsorption. Age of clinical onset is highly variable and some affected individuals are asymptomatic.
Hypomagnesemia 7, renal, with or without dilated cardiomyopathy
An autosomal dominant renal disease characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis. A subset of patients develop severe dilated cardiomyopathy.
Hypomagnesemia, seizures, and impaired intellectual development 1
A disease characterized by renal wasting of magnesium, low serum magnesium, seizures, and variable degrees of delayed psychomotor development.
Hypomagnesemia, seizures, and impaired intellectual development 2
An autosomal dominant disease characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation and are associated with significant intellectual disability.
Hypomyelination with brainstem and spinal cord involvement and leg spasticity
An autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild intellectual disability. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord.
Hypoparathyroidism, familial isolated, 1
A form of hypoparathyroidism, a disorder characterized by hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone. Clinical features include seizures, tetany and cramps. FIH1 inheritance can be autosomal dominant or recessive.
Hypoparathyroidism, familial isolated, 2
An autosomal recessive form of hypoparathyroidism, a disorder characterized by hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone. Clinical features include seizures, tetany and cramps.
Hypoparathyroidism, sensorineural deafness, and renal disease
Hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome
Nephrosis, nerve deafness, and hypoparathyroidism
A disease characterized by steroid-resistant nephrosis with progressive renal failure, hypoparathyroidism, sensorineural deafness, and renal dysplasia.
An X-linked form of true hypoparathyroidism characterized by neonatal or infantile onset and absence of parathyroid glands. Clinical features are hypocalcemia, hyperphosphatemia, seizures, tetany and cramps.
Hypoparathyroidism-retardation-dysmorphism syndrome
An autosomal recessive multisystem disorder characterized by hypoparathyroidism, intrauterine and postnatal growth retardation, psychomotor retardation, epilepsy, microcephaly, and facial dysmorphism.
A metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia).
A bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase.
A severe bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Three more or less distinct types of infantile hypophosphatasia can be identified: (1) type 1 with onset in utero or in early postnatal life, craniostenosis, severe skeletal abnormalities, hypercalcemia, and death in the first year or so of life; (2) type 2 with later, more gradual development of symptoms, moderately severe 'rachitic' skeletal changes and premature loss of teeth; (3) type 3 with no symptoms, the condition being determined on routine studies.
Hypophosphatemic rickets, autosomal dominant
Autosomal dominant vitamin D-resistant rickets
A disease characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses.
Hypophosphatemic rickets, autosomal recessive, 1
A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities.
Hypophosphatemic rickets, autosomal recessive, 2
Hypophosphatemic rickets, X-linked dominant
Hypophosphatemic vitamin D-resistant rickets
A disorder characterized by impaired phosphate uptake in the kidney, which is likely to be caused by abnormal regulation of sodium phosphate cotransport in the proximal tubules. Clinical manifestations include skeletal deformities, growth failure, craniosynostosis, paravertebral calcifications, pseudofractures in lower extremities, and muscular hypotonia with onset in early childhood. X-linked hypophosphatemic rickets is the most common form of hypophosphatemia with an incidence of 1 in 20000.
Hypophosphatemic rickets, X-linked recessive
A renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only.
Hypopigmentation, organomegaly, and delayed myelination and development
An autosomal dominant pleiotropic syndrome characterized by skin and hair hypopigmentation, growth and developmental delay, organomegaly including enlarged liver, spleen and kidneys, delayed brain myelination and developmental deficit in motor skills. Skin and liver biopsies show cellular accumulation of large intracellular vacuoles.
Hypoplasia or aplasia of tibia with polydactyly
Hypoplastic or aplastic tibia with polydactyly
Tibia, hypoplasia or aplasia of, with polydactyly
Tibial hemimelia-polydactyly-triphalangeal thumbs with fibular dimelia
An autosomal dominant disease characterized by hypoplastic or absent tibia, and polydactyly.
An autosomal dominant disorder characterized by isolated bilateral hypoplasia of the femoral and pelvic bones.
A syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged.
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration
Rare syndrome with many clinical similarities to PKAN.
A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome.
Hypotaurinemic retinal degeneration and cardiomyopathy
An autosomal recessive disorder characterized by low plasma taurine, childhood-onset progressive retinal degeneration, and cardiomyopathy.
Hypothyroidism, central, and testicular enlargement
A disorder characterized by insufficient thyroid gland stimulation by thyroid stimulating hormone (TSH), resulting from hypothalamic and/or pituitary dysfunction. CHTE patients have delayed testosterone increase at puberty with normal testosterone levels in adulthood, normal testicular volume in childhood and enlarged testicles in adulthood.
Hypothyroidism, congenital, non-goitrous, 1
Congenital hypothyroidism due to TSH resistance
Hypothyroidism due to unresponsiveness to thyrotropin
A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland.
Hypothyroidism, congenital, non-goitrous, 2
Congenital hypothyroidism due to thyroid dysgenesis
A disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue.
Hypothyroidism, congenital, non-goitrous, 4
A form of central hypothyroidism, a disorder characterized by insufficient stimulation by thyroid stimulating hormone of an otherwise normal thyroid gland. CHNG4 is an autosomal recessive form characterized by isolated thyrotropin deficiency that, if untreated, results in severe growth retardation and intellectual disability.
Hypothyroidism, congenital, non-goitrous, 5
A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. CHNG5 presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland.
Hypothyroidism, congenital, non-goitrous, 6
A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance.
Hypothyroidism, congenital, non-goitrous, 7
Thyrotropin-releasing hormone resistance, generalized
A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by thyrotropin of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG7 is a congenital, autosomal recessive form characterized by normal-to-low T4 and normal-to-high thyrotropin levels, and reduced or absent pituitary responsiveness to thyrotropin-releasing hormone. Patients may exhibit short stature, growth retardation, and delayed bone age, as well as lethargy or fatigue.
Hypothyroidism, congenital, non-goitrous, 8
A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by the thyroid stimulating hormone of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG8 is a congenital, X-linked, relatively mild form which may be accompanied by hearing loss in some patients.
Hypothyroidism, congenital, non-goitrous, 9
A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by thyrotropin of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG9 is a congenital, X-linked recessive form. Patients have a small thyroid gland with low free T4 levels and inappropriately normal levels of thyrotropin.
Hypotonia, ataxia, and delayed development syndrome
An autosomal dominant neurodevelopmental syndrome characterized by global developmental delay, moderate to severe intellectual disability, cerebellar ataxia, hypotonia, speech delay, variable dysmorphic features, and genitourinary abnormalities including vesicoureteric reflux.
Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome
An autosomal dominant disorder characterized by delayed motor development, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects.
Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, poor or absent speech, hypotonia, variable ocular movement and visual abnormalities, and respiratory difficulties. Disease onset is in infancy and death due to respiratory insufficiency may occur.
Hypotonia, infantile, with psychomotor retardation
An autosomal recessive disorder characterized by congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects.
Hypotonia, infantile, with psychomotor retardation and characteristic facies 1
Infantile neuroaxonal neurodegeneration with facial dysmophism
A neurodegenerative disease characterized by variable degrees of hypotonia, speech impairment, intellectual disability, pyramidal signs, subtle facial dysmorphism, and chronic constipation. Some patients manifest neuroaxonal dystrophy, optic atrophy, unmyelinated axons and spheroid bodies in tissue biopsies.
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2
An autosomal recessive, neurodegenerative disease characterized by severe truncal hypotonia since birth or early infancy, progressive peripheral spasticity, and profound psychomotor developmental delay. Some patients may have seizures.
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3
An autosomal recessive neurodevelopmental disorder characterized by profound developmental disability, intellectual disability and severe hypotonia. Many patients have seizures, and show brain atrophy, dysgenesis of the corpus callosum and white-matter changes on neuroimaging. Non-specific facial dysmorphism is noted in some individuals.
Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood.
A rare form of non-syndromic hereditary hypotrichosis without characteristic hair shaft anomalies. Affected individuals typically show normal hair at birth, but hair loss and thinning of the hair shaft start during early childhood and progress with age. HYPT1 inheritance is autosomal dominant.
A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT11 is an autosomal dominant form characterized by scanty or absent eyebrows and a highly variable degree of alopecia since birth, ranging from slight thinning of scalp and axillary hair to complete loss of scalp and body hair. Pubic hair remains mainly unaffected.
A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT12 patients have normal scalp hair density at birth. Hair loss begins during the first 6 months of life and gradually progresses to nearly complete loss of scalp hair. The remaining hairs grow slowly and are thin, sparse, dry, and fragile. Body hair, axillary and pubic hair, eyebrows and eyelashes are also sparse or absent. HYPT12 inheritance is autosomal dominant.
A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT13 is an autosomal dominant form characterized by sparse woolly hair.
A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT14 is an autosomal recessive form characterized by sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair.
A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT15 is an autosomal recessive form characterized by sparse to absent scalp and body hair. Eyebrows and eyelashes may be sparse or absent as well.
A condition characterized by the presence of less than the normal amount of hair. Affected individuals have normal hair in early childhood but experience progressive hair loss limited to the scalp beginning in the middle of the first decade and almost complete baldness by the third decade. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. HYPT2 inheritance is autosomal dominant.
A condition characterized by the presence of less than the normal amount of hair. Affected individuals have normal hair in early childhood but experience progressive hair loss limited to the scalp beginning in the middle of the first decade and almost complete baldness by the third decade. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. HYPT3 inheritance is autosomal dominant.
Marie Unna hereditary hypotrichosis type 1
An autosomal dominant condition characterized by reduced amount of hair, alopecia, little or no eyebrows, eyelashes or body hair, and coarse, wiry, twisted hair in early childhood.
A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT5 is an autosomal dominant form characterized by little or no scalp hair at birth, wiry and irregular scalp hair in childhood, and sparse or no forehead and parietal hair at puberty. Eyebrows and eyelashes are thin, and pubic and axillary hair fails to develop. Scarring alopecia is modest, and vertex hair is normal.
Hypotrichosis localized autosomal recessive
Hypotrichosis localized autosomal recessive 1
A condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed. HYPT6 inheritance is autosomal recessive.
Alopecia universalis congenita Mari type
Hypotrichosis localized autosomal recessive 2
A condition characterized by the presence of less than the normal amount of hair. Affected individuals have sparse or absent scalp, axillary and body hair and sparse eyebrows and eyelashes. HYPT7 inheritance is autosomal recessive.
Hypotrichosis localized autosomal recessive 3
A condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed. HYPT8 inheritance is autosomal recessive.
Hypotrichosis and recurrent skin vesicles
A disorder characterized by hypotrichosis and the appearance of recurrent skin vesicle formation. Affected individuals show sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid are observed on the scalp and skin of most of the body. Mucosal vesicles are absent.
Hypotrichosis congenital with juvenile macular dystrophy
A disorder characterized by congenital hypotrichosis, early hair loss, and severe degenerative changes of the retinal macula that culminate in blindness during the second to third decade of life.
Hypotrichosis-lymphedema-telangiectasia syndrome
A syndrome characterized by absent eyebrows and eyelashes, lymphatic edemas of the inferior members or eyelids, and peripheral vein anomalies.
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome
Glomerulonephritis with sparse hair and telangiectases
Telangiectatic membranoproliferative glomerulonephritis
A syndrome characterized by sparse hair, lymphatic edemas, peripheral vein anomalies, and renal disease.
A disorder characterized by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells, and high urinary urate excretion. Patients often appear asymptomatic, but may be subject to exercise-induced acute renal failure, chronic renal dysfunction and nephrolithiasis.
A rare autosomal dominant skin disorder displaying a type of epidermolytic hyperkeratosis characterized by generalized erythema and extensive blistering from birth. Large, dark gray hyperkeratoses are observed in later weeks. The skin of IBS patients is unusually fragile and has a tendency to shed the outer layers of the epidermis, producing localized denuded areas (molting effect). IBS usually improves with age so that in most middle-aged patients the hyperkeratosis and keratotic lichenification is limited to the flexural folds of the major joints.
An autosomal dominant form of ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling. IHL is characterized by normal skin at birth that develops striking spiny hyperkeratotic lesions within a few months. There is sparing of the face, palms, and soles, and affected individuals do not experience blistering.
A genodermatosis with severe verrucous hyperkeratosis. Affected individuals manifest congenital verrucous black scale on the scalp, neck, and limbs with truncal erythema, palmoplantar keratoderma and keratoses on the lips, ears, nipples and buttocks.
Ichthyosis hystrix-like with deafness syndrome
An autosomal dominant keratinizing disorder characterized by sensorineural deafness and spiky hyperkeratosis affecting the entire skin. HID syndrome is considered to differ from the similar KID syndrome in the extent and time of occurrence of skin symptoms and the severity of the associated keratitis.
A keratinization disorder characterized by complications in the second trimester of pregnancy resulting from polyhydramnion, with premature birth of a child with thick caseous desquamating epidermis, respiratory complications and transient eosinophilia. After recovery during the first months of life, the symptoms are relatively benign and the patients suffer from a lifelong non-scaly ichthyosis with atopic manifestations.
The most common form of ichthyosis inherited as an autosomal dominant trait. It is characterized by palmar hyperlinearity, keratosis pilaris and a fine scale that is most prominent over the lower abdomen, arms, and legs. Ichthyosis vulgaris is characterized histologically by absent or reduced keratohyalin granules in the epidermis and mild hyperkeratosis. The disease can be associated with frequent asthma, eczema or hay fever.
Erythroderma, ichthyosiform, congenital reticular
An autosomal dominant, rare skin condition characterized by slowly enlarging islands of normal skin surrounded by erythematous ichthyotic patches in a reticulated pattern. The condition starts in infancy as a lamellar ichthyosis, with small islands of normal skin resembling confetti appearing in late childhood and at puberty. Histopathologic findings include band-like parakeratosis, psoriasiform acanthosis, and vacuolization of keratinocytes with binucleated cells in the upper epidermis, sometimes associated with amyloid deposition in the dermis. Ultrastructural abnormalities include perinuclear shells formed from a network of fine filaments in the upper epidermis.
Cyclic ichthyosis with epidermolytic hyperkeratosis
A form of annular epidermolytic ichthyosis, an autosomal dominant skin disorder characterized by polycyclic, migratory erythematous and scaly plaques. AEI1 is characterized by the development of widespread erythematous blistering in the neonatal period or early childhood that subsides over time.
A form of annular epidermolytic ichthyosis, an autosomal dominant skin disorder characterized by polycyclic, migratory erythematous and scaly plaques. AEI2 patients manifest erythema and blistering of skin at birth that improves without scarring, as well as palmoplantar keratoderma.
Ichthyosis, congenital, autosomal recessive 1
Autosomal recessive congenital ichthyosis 1 with bathing suit distribution
Autosomal recessive congenital ichthyosis TGM1-related
A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.
Ichthyosis, congenital, autosomal recessive 10
Ichthyosis, congenital, autosomal recessive 11
Autosomal recessive ichthyosis with hypotrichosis
Ichthyosis and follicular atrophoderma with hypotrichosis and hypohidrosis
Ichthyosis, congenital, autosomal recessive 12
Ichthyosis, congenital, autosomal recessive 13
Ichthyosis, congenital, autosomal recessive 14
Ichthyosis, congenital, autosomal recessive 2
Ichthyosiform erythroderma Brocq congenital non-bullous form
Non-bullous congenital ichthyosiform erythroderma type 1
Ichthyosis, congenital, autosomal recessive 3
Ichthyosis, congenital, autosomal recessive 4A
Ichthyosis, congenital, autosomal recessive 4B
Ichthyosis congenita harlequin fetus type
A rare, very severe form of congenital ichthyosis, in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period. Babies who survive into infancy and beyond develop skin changes resembling severe non-bullous congenital ichthyosiform erythroderma.
Ichthyosis, congenital, autosomal recessive 5
Non-lamellar and non-erythrodermic congenital autosomal recessive ichthyosis
Ichthyosis, congenital, autosomal recessive 6
Ichthyosis, congenital, autosomal recessive, ichthyin-related
Ichthyosis, congenital, autosomal recessive, NIPAL4-related
Ichthyosis congenital autosomal recessive
Ichthyosis, congenital, autosomal recessive 8
Ichthyosis, congenital, autosomal recessive 9
Ichthyosis, lamellar, autosomal dominant
An autosomal dominant form of ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling. ADLI is characterized by onset at birth or within the first months of life, skin scaling on the entire body with relative sparing of face, anterior chest, and abdomen, and palmoplantar keratoderma. Patients may manifest mild erythema and moderate pruritus.
Ichthyosis, spastic quadriplegia, and impaired intellectual development
A severe autosomal recessive disorder characterized by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures.
A keratinization disorder manifesting with mild erythroderma and generalized exfoliation of the skin within a few weeks after birth. Affected boys later develop large, polygonal, dark brown scales, especially on the neck, extremities, trunk, and buttocks.
Ichthyosis-sclerosing cholangitis neonatal syndrome
Ichthyosis with leukocyte vacuoles, alopecia and sclerosing cholangitis
A rare autosomal recessive complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, mild diffuse ichthyosis, sclerosing cholangitis and leukocyte vacuolization.
Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies
An autosomal dominant disease characterized by ichthyosis due to epidermal hyperproliferation and increased keratinisation, hypomyelination of the central white matter, spastic paraplegia, central nystagmus, optic atrophy, reduction of peripheral vision and visual acuity, and dysmorphic facial features.
An abnormality of the vertebral column in which patients develop lateral curvature of the spine of at least 10 degrees.
IFAP syndrome 1, with or without Bresheck syndrome
Ichthyosis follicularis, atrichia, and photophobia with or without brain anomalies, retardation, ectodermal dysplasia, skeletal malformations, hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia
Ichthyosis follicularis-atrichia-photophobia syndrome
An X-linked syndrome characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. Histopathologically, the epidermal granular layer is generally well-preserved or thickened at the infundibulum. Hair follicles are poorly developed and tend to be surrounded by an inflammatory infiltrate. A subgroup of patients is described with lamellar rather than follicular ichthyosis. Non-consistent features may include growth and psychomotor retardation, aganglionic megacolon, seizures and nail dystrophy.
An autosomal dominant form of IFAP syndrome, a disease characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. IFAP2 patients manifest ichthyosis follicularis or follicular hyperkeratosis, hyperkeratotic plaques, sparse to no body hair, and photophobia with punctate corneal epithelial defects, corneal pannus, and complicated cataract. Ultrastructural hair analysis shows trichorrhexis nodosa.
Most common primary glomerulonephritis, which is partly due to aberrant or incomplete galactosylation of IgA1 molecules.
A form of IgA nephropathy, a common primary glomerulonephritis characterized by glomerular sclerosis, interstitial fibrosis, and mesangial glomerular deposits of immunoglobulin A and immunoglobulin G visible on renal biopsies. IgA nephropathy is associated with renal insufficiency that can progress to end-stage renal disease. Proteinuria and hematuria are characteristic clinical presentations.
An autosomal dominant syndrome characterized by generalized overgrowth, dysmorphic features, musculoskeletal abnormalities, developmental delay and intellectual disability. Some patients have genitourinary and structural brain abnormalities.
Defect of enterocyte intrinsic factor receptor
Pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin B12, with proteinuria
A form of Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in infancy or early childhood. Clinical manifestations include failure to thrive, infections and neurological damage. Mild proteinuria, with no signs of kidney disease, is present in about half of the patients.
A disorder of renal tubular reabsorption of glycine and imino acids (proline and hydroxyproline), marked by excessive levels of all three substances in the urine.
Immune dysregulation and systemic hyperinflammation syndrome
Hemophagocytic lymphohistiocytosis, familial, 6
An autosomal recessive disorder characterized by systemic hyperinflammation in the absence of an infectious agent or autoimmune trigger. Features include lymphadenopathy, hepatosplenomegaly, recurrent fever, and laboratory evidence of immune dysregulation with abnormal immune cell populations and increased serum levels of inflammatory cytokines.
Immune dysregulation with autoimmunity, immunodeficiency, and lymphoproliferation
Autoimmune lymphoproliferative syndrome 5
Autoimmune lymphoproliferative syndrome type V
An autosomal dominant primary immunodeficiency characterized by severe autoimmunity, infiltration of non-lymphoid organs, such as the intestine, lungs and brain, by hyperactive T cells and B cells, autoimmune cytopenias, and hypogammaglobulinemia in early childhood.
Immune dysfunction with T-cell inactivation due to calcium entry defect 2
An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, lymphadenopathy, and normal lymphocytes counts and serum immunoglobulin levels. Additional features include thrombocytopenia, autoimmune hemolytic anemia, myopathy, partial iris hypoplasia, hepatosplenomegaly and defective enamel dentition.
Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia
Pulmonary alveolar proteinosis with hypogammaglobulinemia
An autosomal dominant disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis in the first months of life. Disease development appears to be influenced or triggered by viral infection. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly.
Immunodeficiency 101, varicella zoster virus-specific
An autosomal dominant immunologic disorder characterized by reactivation of varicella zoster virus (VZV) infection in adulthood after primary childhood infection with VZV. The viral reactivation manifests as central nervous system vasculitis with stroke-like episodes and lacunar infarcts on brain imaging. Features include headache, hemiparesis, impaired balance, and other neurologic signs.
An X-linked recessive disorder characterized by recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopenias that appear in early childhood. Affected individuals have bacterial, viral, and fungal infections, as well as hemolytic anemia, thrombocytopenia, lymphopenia, and decreased NK cells. The disorder may also manifest as a hyperinflammatory state with immune dysregulation.
Immunodeficiency 103, susceptibility to fungal infections
Familial chronic mucocutaneous candidiasis autosomal recessive
An autosomal recessive primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.
Severe combined immunodeficiency autosomal recessive T cell-negative/B cell-positive/NK cell-positive
Severe combined immunodeficiency autosomal recessive T-cell negative/B-cell positive/NK-cell positive
A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.
SCID, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive
An autosomal recessive disorder characterized by recurrent infections in early infancy, decreased or absent numbers of non-functional T cells, normal or increased levels of B cells, hypogammaglobulinemia, and normal or low NK cells. Clinical manifestations may include pneumonia, dermatitis, and lymphadenopathy.
Immunodeficiency 106, susceptibility to viral infections
An autosomal recessive immunologic disorder characterized by increased susceptibility to viral infections beginning in infancy or early childhood. IMD106 affected individuals may demonstrate adverse reactions to vaccination with live attenuated viral vaccines, most notably measles, mumps and rubella (MMR) and yellow fever vaccines. A subset of IMD106 patients develop severe reactions, including excessive hyperinflammatory response, encephalopathy, acute respiratory distress syndrome, and multiorgan failure. IMD106 may also predispose to severe respiratory infection with SARS-CoV-2.
Immunodeficiency 107, susceptibility to invasive Staphylococcus aureus infection
An autosomal dominant immunologic disorder characterized by increased susceptibility to invasive and severe Staphylococcus aureus infection, causing life-threatening skin or pulmonary necrosis. Clinically, penetrance is incomplete and expressivity is variable.
Immunodeficiency 108 with autoinflammation
Pelger-Huet-like anomaly and episodic fever with abdominal pain
An autosomal recessive disorder characterized by autoinflammation and immune impairment of neutrophils, manifesting around adolescence. Affected individuals have recurrent episodes of abdominal pain associated with fever and elevated inflammatory markers. Additional features include recurrent infections, particularly of the skin and nails, poor wound healing, and mild bleeding tendencies.
An autosomal recessive primary immunodeficiency characterized by normal numbers of T and B-lymphocytes, but defective intracellular signaling. There is a block in B-cell differentiation with increased numbers of transitional B-cells and hypogammaglobulinemia, as well as decreased numbers of regulatory T-cells and defects in T-cell function.
Immunodeficiency 11B with atopic dermatitis
Atopic dermatitis, elevated IgE, and eosinophilia
An autosomal dominant disorder of immune dysfunction characterized by onset of moderate to severe atopic dermatitis in early childhood. Some patients may have recurrent infections and other variable immune abnormalities. Laboratory studies show defects in T-cell activation, increased IgE, and eosinophilia.
A primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations include mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Levels of absolute lymphocytes and serum immunoglobulins are normal, but specific antibody titers are low despite immunization, and T-cells show impaired proliferative responses to mitogens.
A rare and heterogeneous syndrome defined by a reproducible reduction in the CD4 T-lymphocyte count (less than 300 cells per microliter or less than 20% of total T-cells) in the absence of HIV infection or other known causes of immunodeficiency. IMD13 predisposes to infections and malignancy.
Immunodeficiency 14A, autosomal dominant
Activated PI3K-delta immunodeficiency syndrome
p110-delta-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency
A disorder characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, reduced immunoglobulin G2 levels in serum, and impaired vaccine responses.
Immunodeficiency 14B, autosomal recessive
An autosomal recessive, primary immunodeficiency characterized by recurrent sinopulmonary infections apparent in early childhood. Some patients may develop inflammatory bowel disease or osteomyelitis. Immunological features include hypogammaglobulinemia, decreased levels of B cells, and evidence of impaired immune-mediated cytotoxicity and defective T-cell function.
An autosomal dominant primary immunodeficiency disorder characterized by lymphopenia, inflammation and immune activation of both CD4+ and CD8+ T cells. Patients suffer from recurrent respiratory tract infections, oral candidiasis, and otitis media.
An autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T-cells, and impaired differentiation and activation of immune cells.
An autosomal recessive primary immunodeficiency associated with classic Kaposi sarcoma of childhood and poor T-cell recall immune responses due to complete functional OX40 deficiency.
SCID-like immunodeficiency, T cell-partial, B cell-positive, NK cell-positive
An autosomal recessive primary immunodeficiency characterized by highly variable clinical severity. Some patients have onset of severe recurrent infections in early infancy that may be lethal, whereas others may be only mildly affected or essentially asymptomatic into young adulthood. More severely affected patients may have evidence of autoimmune disease or enteropathy. The immunologic pattern is similar among patients, showing partial T-cell lymphopenia, decreased amounts of the CD3 complex, and impaired proliferative responses to T-cell receptor dependent stimuli. The phenotype in some patients is reminiscent of severe combined immunodeficiency.
Immunodeficiency 18, severe combined immunodeficiency variant
An autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18.
T cell-negative, B cell-positive, NK cell-positive SCID
T cell-negative, B cell-positive, NK cell-positive severe combined immunodeficiency
An autosomal recessive form of severe combined immunodeficiency characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T-cell negative, B-cell positive, NK-cell positive phenotype.
A rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Affected individuals typically present with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV).
Combined immunodeficiency with susceptibility to mycobacterial viral and fungal infections
Dendritic cell monocyte lymphocyte B and natural killer lymphocyte deficiency
Monocytopenia and mycobacterial infection syndrome
Monocytopenia with susceptibility to mycobacterial fungal and papillomavirus infections and myelodysplasia
An immunodeficiency disease characterized by profoundly decreased or absent monocytes, B-lymphocytes, natural killer lymphocytes, and circulating and tissue dendritic cells, with little or no effect on T-cell numbers. Clinical features of DCML include susceptibility to disseminated non-tuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. This syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern.
A primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive.
Immunodeficiency-vasculitis-myoclonus syndrome
Immunodeficiency with hyper IgE and cognitive impairment
A primary immunodeficiency syndrome characterized by recurrent respiratory and skin infections beginning in early childhood, severe atopy, increased serum IgE, and developmental delay or cognitive impairment of varying severity.
A life-threatening immunodeficiency, characterized by an impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpes viruses, including EBV and varicella zooster virus (VZV), and also suffer from recurrent encapsulated bacterial infections, a spectrum of infections typical of a combined deficiency of adaptive immunity.
Immunodeficiency due to defect in CD3-zeta
An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.
Immunodeficiency 26 with or without neurologic abnormalities
A form of severe combined immunodeficiency characterized by reduced or absent T and B cells, recurrent candidiasis, and lower respiratory tract infections. Some patients show dysmorphic features, severe growth failure, microcephaly, seizures, and impaired neurological functions.
Autosomal recessive immunodeficiency 27A, mycobacteriosis
Familial disseminated atypical mycobacterial infection
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas.
Immunodeficiency 27B, mycobacteriosis, autosomal dominant
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD27B commonly presents with recurrent, moderately severe infections with environmental mycobacteria or BCG. Salmonellosis is present in about 5% of patients.
Immunodeficiency 28, mycobacteriosis, autosomal recessive
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD28 is an autosomal recessive disease that manifests early in life, with severe, often fatal, infection.
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD29 is characterized by undetectable IL12B secretion from leukocytes. Affected individuals generally present with BCG disease after vaccination in childhood, and at least half also have Salmonella infection. Disease phenotype is relatively mild, and patients have a good prognosis.
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD30 has low penetrance, and affected individuals have relatively mild disease and good prognosis. BCG disease and salmonellosis are the most frequent infections in IMD30 patients.
Immunodeficiency 31A, mycobacteriosis, autosomal dominant
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD31A has low penetrance, and affected individuals have relatively mild disease and good prognosis. IMD31A confers a predisposition to mycobacterial infections only, with no increased susceptibility to viral infections.
Autosomal recessive susceptibility to mycobacterial and viral infections
Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive
Mycobacterial and viral infections due to complete STAT1 deficiency
A disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness.
Candidiasis, familial chronic mucocutaneous, autosomal dominant
Autosomal dominant CD11C-positive/CD1C-positive dendritic cell deficiency
Autosomal dominant immunodeficiency 32A, mycobacteriosis
An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections.
Autosomal recessive monocyte and dendritic cell deficiency
Immunodeficiency 32B, monocyte, dendritic cell, and natural killer cell deficiency, autosomal recessive
An autosomal recessive primary immunodeficiency characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis.
Familial, X-linked, atypical mycobacteriosis 1
Recurrent isolated invasive pneumococcal disease 2
X-linked disseminated atypical mycobacterial infection type 1
X-linked immunodeficiency 33, mycobacteriosis
X-linked susceptibility to mycobacterial disease type 1
An X-linked recessive disorder characterized by variably impaired immunologic function and early-onset recurrent infections, usually due to pneumococcus, H. influenzae, and atypical mycobacteria. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia.
Familial, X-linked, atypical mycobacteriosis 2
Familial disseminated atypical mycobacterial infection X-linked 2
Mendelian susceptibility to mycobacterial disease X-linked 2
X-linked immunodeficiency 34, mycobacteriosis
A form of Mendelian susceptibility to mycobacterial disease, a rare condition characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals.
Autosomal recessive HIES with atypical mycobacteriosis
Autosomal recessive hyper-IgE syndrome with atypical mycobacteriosis
A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
A primary immunodeficiency characterized by impaired B-cell function, hypogammaglobulinemia and recurrent infections.
A form of primary combined immunodeficiency, a group of disorders characterized by severe recurrent infections, with normal numbers or an absence of T and B lymphocytes, and impaired cellular and humoral immunity. IMD37 is characterized by hypogammaglobulinemia without lymphopenia, but with profoundly reduced memory B cells and memory T cells, and increased numbers of circulating naive lymphocytes. Inheritance is autosomal recessive.
Immunodeficiency 38, with basal ganglia calcification
Immunodeficiency 38, mycobacteriosis, autosomal recessive
A primary immunodeficiency predisposing individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines. Patients are also susceptible to Salmonella and Mycobacterium tuberculosis infections. Affected individuals have intracranial calcification.
A primary immunodeficiency causing severe, life-threatening acute respiratory distress upon infection with H1N1 influenza A.
A form of combined immunodeficiency characterized by lymphopenia, and defective T-cell, B-cell, and NK-cell responses. Patients suffer from severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation.
Immunodeficiency 41 with lymphoproliferation and autoimmunity
A disorder of immune dysregulation characterized by recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions.
An autosomal recessive primary immunodeficiency characterized by increased susceptibility to concomitant candidiasis and mycobacteriosis. Candidiasis is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida. Mycobacteriosis is characterized by infections caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. IMD42 patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections.
A disorder characterized by marked reduction in serum concentrations of immunoglobulins and albumin, and hypoproteinemia due to hypercatabolism. Patients may suffer from recurrent respiratory tract infections and severe skin disease.
An autosomal recessive disorder characterized by increased susceptibility to viral infection, resulting in some patients in encephalopathy and infection-associated neurologic decompensation.
An autosomal recessive disorder characterized by increased susceptibility to viral infection due to impaired antiviral immunity, resulting in infection-associated encephalopathy. Affected individuals are at risk for developing fatal encephalitis after routine measles/mumps/rubella (MMR) vaccination.
An autosomal recessive primary immunodeficiency disorder characterized by early-onset chronic diarrhea, recurrent infections, hypo- or agammaglobulinemia, normal lymphocyte counts, intermittent neutropenia, and intermittent thrombocytopenia.
Congenital disorder of glycosylation, type IIs
Immunodeficiency and hepatopathy with or without neurologic features
A complex immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, defective glycosylation of serum proteins, and liver disease with neonatal jaundice and hepatosplenomegaly. Some patients may also have neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities. Inheritance is X-linked recessive.
A form of severe immunodeficiency characterized by a selective absence of CD8+ T-cells.
SCID, T cell-negative, B cell-positive, NK cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities
SCID, T-cell-negative, B-cell-positive, NK-cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities
Severe combined immunodeficiency, T cell-negative, B cell-positive, NK cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities
A form of severe combined immunodeficiency characterized by severe T-cell lymphopenia, no detectable T-cell receptor excision circles, no naive helper CD4+ T-cells, and impaired T-cell proliferative response. In addition to primary immunodeficiency, affected individuals manifest multiple abnormal systemic features, including severe delayed psychomotor development, intellectual disability, spastic quadriplegia, and craniofacial abnormalities.
A primary immunodeficiency disorder characterized by onset of recurrent bacterial or varicella zoster virus infections in early childhood, profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, and a poor immune response to vaccine antigens.
Candidiasis familial 5 autosomal recessive
An autosomal recessive primary immunodeficiency characterized by T-cell abnormalities, resulting in severe combined immunodeficiency, autoimmune disease, progressive lymphopenia and hypogammaglobulinemia, and lymphoproliferation with splenomegaly. Patients develop severe recurrent infections from infancy.
An autosomal recessive primary immunodeficiency apparent from early infancy and resulting in recurrent infections, severe autoimmune skin disease rheumatoid arthritis, and failure to thrive. Immunologic workup shows increased CD4+/CD8+ ratio, impaired T-cell proliferative response to multiple antigen, T-cell developmental and functional defects, and impaired ability to produce specific immunoglobulins.
Familial isolated natural killer cell deficiency
Natural killer cell and glucocorticoid deficiency with DNA repair defect
An autosomal recessive disorder characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer.
An autosomal recessive primary immunodeficiency characterized by chronic neutropenia, natural killer cell deficiency, recurrent viral and bacterial infections, and intrauterine growth retardation. Postnatal growth retardation is present in most patients.
Autosomal recessive primary immunodeficiency IL21R-related
An autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B-cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens.
Immunodeficiency 57 with autoinflammation
An autosomal recessive primary immunodeficiency characterized by lymphopenia and recurrent viral, bacterial, and fungal infections. Patients exhibit early-onset inflammatory bowel disease involving the upper and lower gastrointestinal tract, and develop progressive polyarthritis.
An autosomal recessive primary immunodeficiency characterized by a variety of infectious diseases, including mycobacterial diseases, mucocutaneous candidiasis, silent but detectable EBV viremia, and staphylococcal diseases. Patients suffer from dermatitis, esophagitis, recurrent skin abscesses and chest infections. Immunologic analysis shows defective T-cell function and deficient CD3/CD28 stimulation responses in both CD4+ and CD8+ T cells. B-cell function may also be impaired.
Granulocytopenia with immunoglobulin abnormality
An autosomal recessive primary immunologic disorder characterized by combined immunodeficiency, granulocytopenia, B-cell and dendritic cell deficiency, recurrent septic infections of the respiratory tract, skin and mucous membranes, and disturbed glucose metabolism.
Immunodeficiency and autoimmunity, BACH2-related
An autosomal dominant primary immunologic disorder characterized by intestinal inflammation, recurrent sino-pulmonary infections, impaired lymphocyte maturation, and variably decreased immunoglobulin production.
An X-linked recessive primary immunologic disorder characterized by recurrent infections due to impaired antibody production. Affected individuals have normal numbers of circulating B and T cells, but B cells have an intrinsic defect in antibody production. Disease severity is variable and onset is in early childhood.
An autosomal recessive, primary immunologic disorder characterized by recurrent severe respiratory tract infections and bronchiectasis, due to antibody deficiency. Affected individuals have an abnormal B cell immunophenotype, with low levels of circulating memory B cells.
Immunodeficiency 63 with lymphoproliferation and autoimmunity
Deficiency of interleukin 2 receptor beta
An autosomal recessive disorder characterized by immune dysregulation resulting in lymphoid proliferation, dermatitis, enteropathy, autoantibodies, hypergammaglobulinemia, and immunodeficiency with recurrent infections. Patients show increased susceptibility to viral infections, particularly cytomegalovirus disease.
An autosomal recessive primary immunodeficiency characterized by recurrent bacterial, viral and fungal infections, variably decreased numbers of T cells, deficiencies of B and NK cells, and increased susceptibility to Epstein-Barr virus (EBV) infection. Patients may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity.
Immunodeficiency 65, susceptibility to viral infections
An autosomal recessive immunologic disorder characterized by recurrent viral infections from early infancy. Clinical consequences are pneumonia, bronchiectasis, and septic shock. Affected individuals have lymphopenia or hypogammaglobulinemia, particularly during infection, and impaired cellular type I interferon response. Patients may have adverse response to vaccination with live attenuated vaccines.
An autosomal recessive primary immunologic disorder characterized by recurrent viral infections from infancy, associated with impaired neutrophil migration due to defects in cytoskeletal actin dynamics.
Recurrent isolated invasive pneumococcal disease 1
An autosomal recessive primary immunodeficiency characterized by recurrent, life-threatening systemic and invasive bacterial infections beginning in infancy or early childhood.
Recurrent pyogenic bacterial infections due to MYD88 deficiency
An autosomal recessive primary immunodeficiency characterized by life-threatening, often recurrent, pyogenic bacterial infections, including invasive pneumococcal disease, beginning in infancy or early childhood.
Immunodeficiency 69, mycobacteriosis, autosomal recessive
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. IMD69 is an autosomal recessive disorder manifesting with fever, hepatosplenomegaly, leukocytosis, and thrombocytosis during the acute infection.
Immunodeficiency 7, TCR-alpha/beta deficient
A primary immunodeficiency disorder manifesting with recurrent respiratory infections, candidiasis, diarrhea, and failure to thrive. Patients show a clear predisposition to herpes viral infections, and features of immune dysregulation, including hypereosinophilia, vitiligo, and alopecia areata. Other features include lymphadenopathy and hepatosplenomegaly. CD3+ T-cells express TCR-gamma/delta, but little or no TCR-alpha/beta.
A primary immunodeficiency clinically characterized by human papillomavirus-associated warts on the hands, feet and face, recurrent bacterial infections, and autoinflammatory features, such as colitis, celiac disease, and retinal vasculitis. Immunologic workup shows decreased CD4+ T cells, decreased CD19+ B cells, and hypogammaglobulinemia. IMD70 inheritance is autosomal dominant with incomplete penetrance.
Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia
Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease
An autosomal recessive disorder characterized by platelet abnormalities, vasculitis, eosinophilia, and predisposition to inflammatory diseases.
Immunodeficiency 72 with autoinflammation
An autosomal recessive immunologic disorder characterized by onset in the first year of life, recurrent bacterial and viral skin infections, severe respiratory tract infections leading to pneumonia and bronchiectasis, and poor specific antibody responses. Patients also exhibit atopic and inflammatory disease alongside chronic hepatosplenomegaly and lymphadenopathy, and autoimmune manifestations.
Immunodeficiency 73A with defective neutrophil chemotaxis and leukocytosis
An autosomal dominant immunologic disorder characterized by onset of recurrent infections in early infancy, leukocytosis, neutrophilia, invasive infections, and poor wound healing.
Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopenia
An autosomal dominant immunologic disorder characterized by respiratory infections, cellulitis, severe invasive infections, B- and T-cell lymphopenia, and impaired neutrophil chemotaxis. Disease onset is in infancy or early childhood.
Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinemia
An autosomal recessive immunologic disorder characterized by recurrent respiratory infections, decreased B cells, hypogammaglobulinemia, and impaired neutrophil chemotaxis. Variable features are urticaria, recurrent erythematous plaques, food allergy, arthralgia, bronchiectasis, and lymphadenopathy. In addition, patients suffer from glomerulonephritis, coagulopathy, multiple hormone deficiencies, and abnormalities of neutrophil granules.
Immunodeficiency 74, COVID19-related, X-linked
Respiratory insufficiency due to SARS-CoV-2 viral infection
An X-linked recessive immunologic disorder characterized by impaired type I and type II interferon responses due to defective TLR7 signaling. Individuals with TLR7 deficiency develop severe respiratory insufficiency in response to infection with SARS-CoV-2 coronavirus. Death from respiratory failure may occur.
An autosomal recessive immunologic disorder characterized by recurrent infections, mainly viral and affecting the respiratory tract, immunodeficieny, immune dysregulation, and the development of lymphoproliferative disorders, including lymphoma.
An autosomal recessive immunologic disorder characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Affected individuals have T-cell lymphopenia and variable B-cell or immunoglobulin abnormalities. Some patients develop B-cell lymphoma, others manifest neurologic features.
An autosomal dominant disorder characterized by recurrent, persistent bacterial and fungal infections with multiple unusual organisms. Skin and pulmonary infections are the most common. Patient macrophages show impaired killing of intracellular bacteria and organisms, including non-tubercular mycobacteria, Pseudomonas, Candida, and Aspergillus.
Immunodeficiency 78 with autoimmunity and developmental delay
An autosomal recessive disorder characterized by immune dysregulation, increased susceptibility to bacterial, viral and fungal infections, recurrent sinopulmonary or skin infections, and autoimmune abnormalities including hemolytic anemia and autoimmune cytopenias. Patients also have global developmental delay with speech delay and variable intellectual disability. Disease onset is in infancy or early childhood.
An autosomal recessive disorder characterized by childhood onset of recurrent and recalcitrant skin warts due to uncontrolled viral infection with human papillomavirus (HPV). Some patients may also have recurrent respiratory infections. Laboratory studies show a complete absence of CD4+ T cells.
A disease of the immune system leading to recurrent infections, and characterized by CD4+ T-cells lymphopenia. Patients can develop B-cell lymphoproliferation associated with Epstein-Barr virus infection.
Immunodeficiency 80 with or without congenital cardiomyopathy
An autosomal recessive immunologic disorder with variable manifestations including decreased B and T cells, reduced effector and memory T cells, NK cell deficiency, chronic cytomegalovirus infection. Restrictive cardiomyopathy and hypoplasia of the spleen and thymus have also been reported in some patients.
An autosomal recessive disorder characterized by recurrent infections, including fungal infections, associated with T cell, neutrophil, and NK cell dysfunction. B cells may also show maturation abnormalities. Other features include autoimmune hemolytic anemia and abnormal platelet aggregation.
Immunodeficiency 82 with systemic inflammation
An autosomal dominant immunologic disorder with onset in early childhood. It is characterized by recurrent infections with various organisms, and multi-organ inflammation that manifests as colitis, hepatitis, arthritis and dermatitis. Patients have a propensity for the development of lymphoma, usually in adulthood. Disease severity is variable.
Immunodeficiency 83, susceptibility to viral infections
Encephalopathy, acute, infection-induced, 2
Encephalopathy, acute, infection-induced, 2, herpes-specific
Infection-induced acute encephalopathy 2
TLR3-deficient herpes simplex encephalitis
An immunologic disorder characterized by increased susceptibility to severe viral infections, including herpes simplex virus (HSV), varicella zoster virus (VZV), influenza A virus (IAV), hantavirus, and possibly respiratory syncytial virus (RSV). IMD83 clinical manifestations include acute infection-induced encephalitis and pneumonitis. The susceptibility to encephalitis or pneumonitis appears to result from impaired TLR3-dependent interferon production by nonhematopoietic cells that reside within the central nervous system or lung epithelial cells. IMD83 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance with incomplete penetrance.
An autosomal recessive immunologic disorder characterized by recurrent sinopulmonary infections from childhood associated with low levels of B cells and impaired early B-cell development. There may also be variable T-cell abnormalities. Patients have increased susceptibility to infection with Epstein-Barr virus and a propensity for the development of lymphoma in adulthood.
An autosomal dominant immunologic disorder characterized by early-onset autoimmunity and features of combined immunodeficiency such as hypogammaglobulinemia and abnormal T-cell function. Clinical manifestations include atopic eczema and recurrent respiratory infections in the first decade of life, autoimmune enteropathy, growth failure, autoimmune oligoarthritis, interstitial pneumonitis, and EBV viremia.
Immunodeficiency 86, mycobacteriosis, autosomal recessive
An autosomal recessive disorder characterized by susceptibility to mycobacterial disease after exposure to BCG vaccine. Affected individuals usually develop localized mycobacterial lymphadenopathy.
An autosomal recessive disorder with onset in infancy or early childhood. It is characterized by increased susceptibility to infections, often Epstein-Barr virus, as well as lymphadenopathy or autoimmune manifestations, predominantly hemolytic anemia. The disorder results primarily from defects in T-cell function.
Immunodeficiency 88, mycobacteriosis, autosomal recessive
An autosomal recessive disorder characterized by the development of disseminated mycobacterial disease following vaccination with BCG. Clinical features included fever, lymphadenopathy, and cutaneous eruption.
An autosomal recessive disorder characterized by adult onset of recurrent infections, allergies, microcytic anemia, and Crohn disease.
Immune dysfunction with T-cell inactivation due to calcium entry defect 1
Severe combined immunodeficiency due to CRAC channel dysfunction
An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhidrosis and non-progressive myopathy may be observed.
Immunodeficiency 91 and hyperinflammation
An autosomal recessive disorder characterized by immunodeficiency, recurrent infections, and hyperinflammation with systemic involvement. Most patients eventually develop hepatic or renal failure, may have compromised neurologic function, lymphadenopathy or hepatosplenomegaly. Early death often occurs due to multiorgan failure.
An autosomal recessive disorder characterized by recurrent bacterial, viral, fungal, or parasitic infections appearing in infancy or early childhood. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.
Immunodeficiency 93 and hypertrophic cardiomyopathy
An autosomal recessive disorder characterized by onset of recurrent viral and bacterial infections, particularly with encapsulated bacteria, and hypertrophic cardiomyopathy in the first months or years of life.
Immunodeficiency 94 with autoinflammation and dysmorphic facies
An autosomal dominant disorder characterized by onset in early infancy, lymphadenopathy, autoinflammation, immunodeficiency with hypogammaglobulinemia, and dysmorphic facial features.
An autosomal recessive disorder characterized by the onset of recurrent and severe viral respiratory infections in infancy or early childhood, and impaired interferon production during viral infection.
An autosomal recessive disorder characterized by onset of recurrent, usually viral, respiratory infections in infancy or early childhood. Other infections, including gastrointestinal and urinary tract infections, may also occur. Laboratory studies show hypogammaglobulinemia, lymphopenia with increased gamma/delta T cells, and erythrocyte macrocytosis.
Immunodeficiency 97 with autoinflammation
An autosomal recessive disorder with variable features. Affected individuals have childhood-onset antibody defects, cytopenias, and T lymphocytic pneumonitis and colitis. Some patients may have features of hemophagocytic lymphohistiocytosis.
Immunodeficiency 98 with autoinflammation, X-linked
Inflammation, neutropenia, bone marrow failure, and lymphoproliferation caused by TLR8
An X-linked disorder characterized by onset of recurrent infections associated with lymphoproliferation and autoinflammation in the first decade of life. Mostly males are affected; carrier females may have mild symptoms. Features include mouth ulcers, fever, poor early growth, hepatosplenomegaly, lymphadenopathy, polyarthritis, and non-infectious enteritis.
Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias
An autosomal recessive immunologic disorder characterized by recurrent sinopulmonary infections appearing in early childhood, B- and T-cell lymphopenia, and progressive severe hypogammaglobulinemia with decreased memory B cells. Patients may develop autoimmune cytopenias, such as thrombocytopenia, or autoimmune features, such as vitiligo.
Immunodeficiency due to defect in MAPBP-interacting protein
This form of primary immunodeficiency syndrome includes congenital neutropenia, partial albinism, short stature and B-cell and cytotoxic T-cell deficiency.
Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome
X-linked autoimmunity-immunodeficiency syndrome
Characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy.
A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.
X-linked immunodeficiency with hyper-IgM 1
Immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.
A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.
Common variable immunodeficiency with central adrenal insufficiency
Deficit in anterior pituitary function and variable immunodeficiency
A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency.
Immunodeficiency, common variable, 12, with autoimmunity
A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly.
A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. CVID13 is an autosomal dominant disease associated with a striking decrease in B-cell numbers.
A primary immunodeficiency resulting in recurrent sinopulmonary infections since early childhood, and characterized by hypogammaglobulinemia with undetectable IgG and IgA, poor response to vaccination, and decreased levels of switched memory B cells. CVID14 inheritance is autosomal dominant.
Hypogammaglobulinemia due to TACI deficiency
Immunodeficiency, common variable, 8, with autoimmunity
An autosomal recessive immunologic disorder associated with defective B-cell differentiation and decreased or absent antibody production. Affected individuals have early-childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease.
Immunodeficiency, developmental delay, and hypohomocysteinemia
An early onset multisystem disorder characterized by immunodeficiency, recurrent infections, developmental delay, poor growth, intellectual disability, and hypohomocysteinemia. Some patients manifest congenital cardiac defects. IMDDHH inheritance pattern is autosomal dominant.
Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia
A disease characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation.
Immunodeficiency-centromeric instability-facial anomalies syndrome 1
Centromeric instability immunodeficiency syndrome
Variable immune deficiency with centromeric instability of chromosomes 1 9 and 16
A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients.
Immunodeficiency-centromeric instability-facial anomalies syndrome 2
Immunodeficiency-centromeric instability-facial anomalies syndrome 3
Immunodeficiency-centromeric instability-facial anomalies syndrome 4
Selective deficiency of immunoglobulin A (IGAD) is the most common form of primary immunodeficiency, with an incidence of approximately 1 in 600 individuals in the western world. Individuals with symptomatic IGAD often have deficiency of IgG subclasses or decreased antibody response to carbohydrate antigens such as pneumococcal polysaccharide vaccine. Individuals with IGAD also suffer from recurrent sinopulmonary and gastrointestinal infections and have an increased incidence of autoimmune disorders and of lymphoid and non-lymphoid malignancies. In vitro studies have suggested that some individuals with IGAD have impaired isotype class switching to IgA and others may have a post-switch defect. IGAD and CVID have been known to coexist in families. Some individuals initially present with IGAD1 and then develop CVID. These observations suggest that some cases of IGAD and CVID may have a common etiology.
Immunoglobulin kappa light chain deficiency
A disease characterized by the complete absence of immunoglobulin kappa chains.
Immunoskeletal dysplasia with neurodevelopmental abnormalities
An autosomal recessive disorder characterized by variable skeletal abnormalities and neurodevelopmental defects. Neurologic manifestations include intellectual disability and motor delay. Some patients manifest hypotonia and seizures. Skeletal features include disproportionate short stature, cervical malformations, epiphyseal and metaphyseal dysplasia, and rarely premature craniosynostosis with progressive microcephaly. Severe combined immunodeficiency with a complete absence of T cells is observed in some patients.
Impaired intellectual development and distinctive facial features with or without cardiac defects
An autosomal dominant syndrome characterized by intellectual disability, delayed psychomotor development, profound language impairment, and facial dysmorphism, including frontal bossing, upslanting palpebral fissures, depressed nasal bridge with bulbous tip, and macrostomia. There is variable penetrance of cardiac malformations, ranging from no malformations to patent foramen ovale to septal defects and/or transposition of the great arteries.
Impaired intellectual development, anterior maxillary protrusion, and strabismus
A syndrome characterized by severe intellectual disability, strabismus and dysmorphic features such as anterior maxillary protrusion with vertical maxillary excess, open bite and prominent crowded teeth. Some patients may lack dysmorphic features and manifest temporal lobe epilepsy and psychosis. Esotropia and amblyopia are present in some individuals.
Impaired intellectual development, truncal obesity, retinal dystrophy, and micropenis
An autosomal recessive disorder characterized by moderate intellectual disability, truncal obesity, congenital non-progressive retinal dystrophy, and micropenis in males. The phenotype is similar to Bardet-Biedl syndrome and Cohen syndrome Distinguishing features are the age of onset, the non-progressive nature of the visual impairment, lack of dysmorphic facies, skin or gingival infection, microcephaly, mottled retina, polydactyly, and testicular anomalies.
Inclusion body myopathy and brain white matter abnormalities
An autosomal dominant, adult-onset disorder characterized predominantly by proximal limb girdle muscle weakness affecting the lower and upper limbs and resulting in gait difficulties and scapular winging. Additional features may include dysarthria, dysphagia, low back pain, and hyporeflexia. Muscle biopsy shows fiber type variation, internal nuclei, rimmed vacuoles, and cytoplasmic protein aggregates or inclusions. Cognitive impairment or frontotemporal dementia occurs in some patients.
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1
Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia
Limb-girdle muscular dystrophy with Paget disease of bone
Lower motor neuron degeneration with Paget-like bone disease
An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance.
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3
Familial incontinentia pigmenti male-lethal type
A genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.
Indifference to pain, congenital, autosomal recessive
Channelopathy-associated insensitivity to pain
Congenital analgesia autosomal recessive
A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating.
Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development
An autosomal dominant disease characterized by infantile-onset cataract, erythematic subcutaneous nodules, profound developmental delay, self-injurious behavior, and intracerebral glutamate excess. Histopathologic analysis of skin lesions show deep perivascular and periglandular lymphohistiocytic infiltrates and pronounced leukocytoclasia at the surface of the dermis, focal vacuolar alterations, hyperkeratosis, and parakeratosis of the epidermis.
Infantile cerebellar-retinal degeneration
A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration.
A life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis.
A form of infantile liver failure syndrome, a life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis.
A form of infantile liver failure syndrome, a life-threatening disorder of hepatic function that manifests with acute liver failure in the first months or years of life. ILFS3 is an autosomal recessive form characterized by recurrent episodes of acute liver failure often triggered by infection or fever. Affected individuals also have skeletal anomalies of the vertebral bodies and femoral heads.
Severe form of sialic acid storage disease. Affected newborns exhibit visceromegaly, coarse features and failure to thrive immediately after birth. These patients have a shortened life span, usually less than 2 years.
Neurological disorder characterized by symmetrical degeneration of the caudate nucleus, putamen, and occasionally the globus pallidus, with little involvement of the rest of the brain. The clinical features include developmental regression, choreoathetosis, dystonia, spasticity, dysphagia, failure to thrive, nystagmus, optic atrophy, and intellectual disability.
Infantile-onset ascending spastic paralysis
Characterized by progressive spasticity and weakness of limbs.
Infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations
A condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and elevated IL10 and FASL levels. Affected individuals suffer from recurrent, stereotypical episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. The episodes can be triggered by varicella zoster virus (VZV), measles mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and Epstein-Barr virus (EBV).
Inflammatory bowel disease (Crohn disease) 1
A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.
Inflammatory bowel disease (Crohn disease) 10
Inflammatory bowel disease (Crohn disease) 19
Inflammatory bowel disease 25, autosomal recessive
Early-onset autosomal recessive inflammatory bowel disease
Inflammatory bowel disease 28, autosomal recessive
A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology and a multifactorial inheritance pattern. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.
Inflammatory bowel disease 31, autosomal recessive
Inflammatory bowel disease, early-onset, autosomal recessive
Inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive
A form of inflammatory bowel disease, a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology and a multifactorial inheritance pattern. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. IBD31 patients suffer from infantile ulcerative colitis and present with recurrent bloody diarrhea with anemia and leukocytosis, extensive lymphoplasmocytic infiltration, cryptitis, and apoptotic crypt abcesses throughout the colon and rectum.
Inflammatory bowel disease, immunodeficiency, and encephalopathy
An autosomal recessive disorder characterized by severe infantile inflammatory bowel disease manifesting as bloody diarrhea and failure to thrive, global developmental delay, epilepsy, brain atrophy and encephalopathy. Affected individuals suffer from recurrent infections associated with impaired T-cell response to stimulation and decreased T-cell subsets, including regulatory and helper T cells.
Inflammatory demyelinating polyneuropathy
Putative autoimmune disorder presenting in an acute (AIDP) or chronic form (CIDP). The acute form is also known as Guillain-Barre syndrome.
Inflammatory poikiloderma with hair abnormalities and acral keratoses
An autosomal recessive disorder characterized by mottled hyper- and hypopigmentation of the skin, sparse scalp hair and eyelashes, sparse or absent eyebrows, and palmoplantar keratoses.
Inflammatory skin and bowel disease, neonatal, 1
A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.
Inflammatory skin and bowel disease, neonatal, 2
Inosine triphosphate pyrophosphohydrolase deficiency
A common inherited condition characterized by the abnormal accumulation of inosine triphosphate in erythrocytes. It might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs.
Resistance to insulin-like growth factor I
A disorder characterized by intrauterine growth retardation, poor postnatal growth and increased plasma IGF1 levels.
Autosomal recessive disorder characterized by growth retardation, sensorineural deafness and intellectual disability.
Insulin-resistant diabetes mellitus with acanthosis nigricans type A
Characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor.
An autosomal dominant disorder characterized by the occurrence of multicentric insulinomas, hyperinsulinemic hypoglycemia, non insulin-dependent diabetes mellitus, and impaired glucose tolerance. Some patients also exhibit congenital cataract and/or congenital glaucoma.
Intellectual developmental disorder and retinitis pigmentosa
An autosomal recessive disease characterized by mild to moderate intellectual disability, retinitis pigmentosa, and attention-deficit hyperactivity disorder observed in some patients.
Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature
An autosomal recessive disorder characterized by intellectual disability, developmental delay with poor or absent speech, short stature, progressive microcephaly, hyperactivity and aggressive behavior. Some patients manifest sensorineural hearing loss.
Intellectual developmental disorder with autism and dysmorphic facies
An autosomal recessive neurodevelopmental disorder characterized by moderate to severe intellectual disability with autistic features, myopathy, and facial dysmorphism.
Intellectual developmental disorder with autism and macrocephaly
An autosomal dominant disorder characterized by impaired intellectual development, a highly penetrant autism spectrum phenotype, and macrocephaly. Other common features include tall stature, gastrointestinal symptoms, distinct facial features, sleep problems, and attention problems.
Intellectual developmental disorder with autism and speech delay
An autosomal dominant neurodevelopmental disorder characterized by varying degrees of intellectual disability, autism spectrum disorder, and language deficits.
Intellectual developmental disorder with autistic features and language delay, with or without seizures
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, varying degrees of intellectual disability, autism spectrum disorder, and delayed language. Some patients develop seizures.
Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures
Neurodevelopmental disorder with macrocephaly and with or without seizures
An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, developmental delay of varying severity, impaired motor skills and language delay. Additional clinical features include macrocephaly, obesity, overgrowth, craniofacial dysmorphism, epilepsy, and variable behavioral manifestations including autism and attention deficit hyperactivity disorder.
Intellectual developmental disorder with cardiac arrhythmia
An autosomal recessive multisystem disorder characterized by delayed psychomotor development, severe intellectual disability with poor or absent speech, and bradycardia and/or cardiac sinus arrhythmias. Additional features include visual abnormalities, seizures, hypotonia, and gastric reflux.
Intellectual developmental disorder with cardiac defects and dysmorphic facies
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, congenital heart malformations, and facial dysmorphism. Dysmorphic features include triangular face, deep set eyes, broad nasal root and tip and anteverted nostrils, thick arched eye brows, hypertrichosis, pointed chin, and hypertelorism.
Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities
An autosomal dominant developmental disorder with variable manifestations and onset in infancy or first years of life. Clinical features include intellectual disability, speech delay, hyperkinetic disorder, hyperactivity, seizures, pre- and postnatal growth retardation, microcephaly, and facial dysmorphism.
Intellectual developmental disorder with dysmorphic facies and ptosis
An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and facial dysmorphisms, most notably ptosis. Additional features may include poor growth, hypotonia, and seizures.
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies
An autosomal recessive severe multisystem disorder characterized by poor overall growth, developmental delay, early-onset seizures, intellectual disability, and dysmorphic features. Additional features include microcephaly, absent speech, hypotonia, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features.
Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies
An autosomal recessive neurodevelopmental disorder that manifests in early infancy with infantile spasms and developmental delay. Clinical features include severely impaired intellectual development, epilepsy, autism, hyperactivity and other behavioral problems, and coarse facies. Brain MRI findings may include delayed myelination in the deep parietal lobes.
Intellectual developmental disorder with hypertelorism and distinctive facies
An autosomal dominant neurodevelopmental disorder characterized by developmental delay and intellectual disability, language defects, and distinctive facial dysmorphism including high hairline, hypertelorism, thin eyebrows, dysmorphic ears, broad nasal bridge and tip, and narrow jaw.
Intellectual developmental disorder with hypotonia and behavioral abnormalities
An autosomal dominant neurodevelopmental disorder with onset in infancy. IDDHBA is characterized by hypotonia, global developmental delay, learning disability, and behavioral abnormalities, such as autistic features and attention deficit-hyperactivity disorder. Additional variable features may include non-specific facial dysmorphism, congenital heart defects, ocular anomalies, and poor feeding.
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, hypotonia, ophthalmologic abnormalities, and non-specific dysmorphic features. Some affected individuals have seizures, and a few have involvement of other organ systems.
Intellectual developmental disorder with impaired language and dysmorphic facies
An autosomal dominant disorder characterized by intellectual disability, developmental delay, impaired language development, and dysmorphic features including telecanthus, epicanthus, arched eyebrows and low-set ears. Additional features include feeding difficulties, mild cardiac or genitourinary defects, and distal skeletal anomalies.
Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
An autosomal dominant disorder characterized by global developmental delay affecting motor, cognitive, and speech domains apparent in early childhood or infancy. Most patients also show movement abnormalities, often hypotonia with later development of dopa-responsive dystonia or parkinsonism. About half of patients develop various types of seizures.
Intellectual developmental disorder with language impairment and with or without autistic features
A developmental disorder characterized by mild to moderate intellectual disability, language impairment, and autistic features in some patients. Patients show global delay, delayed walking, severely delayed speech development, and behavioral abnormalities, including irritability, hyperactivity, aggression, and stereotypical rigid behaviors.
Intellectual developmental disorder with macrocephaly, seizures, and speech delay
An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures.
Intellectual developmental disorder with microcephaly and pontine and cerebellar hypoplasia
Intellectual developmental disorder, X-linked, syndromic, Najm type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Affected individuals can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of intellectual disability alone or associated with nystagmus.
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects
An autosomal recessive disorder characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability.
Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies
An autosomal dominant disorder characterized by delayed development, speech delay with nasal speech, and characteristic facial features including upslanted palpebral fissures, anteverted nares, a thin upper lip, and micrognathia. Some patients may have skeletal anomalies, such as brachydactyly, toe syndactyly and flat feet.
Intellectual developmental disorder with neuropsychiatric features
An autosomal recessive disorder characterized by moderate to severe intellectual disability, epilepsy, and variable neuropsychiatric features, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphism may also be present.
Intellectual developmental disorder with ocular anomalies and distinctive facial features
An autosomal dominant disorder characterized by global developmental delay, mild intellectual disability, ophthalmologic anomalies, microcephaly or relative microcephaly, hearing loss, and characteristic facial features including long, upslanting palpebral fissures, bitemporal narrowing of the forehead, arched eyebrows, and epicanthal folds.
Intellectual developmental disorder with or without epilepsy or cerebellar ataxia
An autosomal dominant neurodevelopmental disorder that manifests with variable features of mild-to-severe intellectual disability, developmental delay, autism spectrum disorder, cerebellar ataxia and epilepsy.
Intellectual developmental disorder with or without peripheral neuropathy
An autosomal recessive disorder characterized by global developmental delay appearing in infancy or early childhood, intellectual disability, and progressive sensorimotor neuropathy with associated distal weakness. Affected individuals have hypotonia and delayed walking with an unsteady gait and frequent falls. Additional features may include dysarthria and subtle facial dysmorpism.
Intellectual developmental disorder with paroxysmal dyskinesia or seizures
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, language delay, and early-onset paroxysmal hyperkinetic movement disorder that manifests as sudden falls or backward propulsion, eye or head deviation, and dystonic limb posturing followed by chorea and dyskinetic movements. Some patients may also develop epileptic seizures or only have seizures without a movement disorder.
Intellectual developmental disorder with persistence of fetal hemoglobin
Intellectual developmental disorder with hereditary persistence of fetal hemoglobin
An autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability, variable dysmorphic features, including microcephaly, downslanting palpebral fissures, strabismus, and external ear abnormalities, and asymptomatic persistence of fetal hemoglobin.
Intellectual developmental disorder with poor growth and with or without seizures or ataxia
An autosomal recessive disorder characterized by global developmental delay apparent from infancy, impaired intellectual development, hypotonia, and poor overall growth with microcephaly. Additional variable features include dysmorphic features, cataracts, ataxia and seizures.
Intellectual developmental disorder with seizures and language delay
An autosomal dominant neurodevelopmental disorder characterized by mild to profound intellectual development impairment, speech and language delay, and seizures. Autism and anxiety are common features. Facial dysmorphism, tapering fingers, and pigmentary skin changes may also be observed.
Intellectual developmental disorder with severe speech and ambulation defects
An autosomal dominant neurodevelopmental disorder with onset in infancy, and characterized by global developmental delay, intellectual disability, ambulation deficits, severe language impairment, and minor dysmorphic features including a wide mouth, diastema, and bulbous nose. Additional manifestations are spasticity, hypotonia and autistic features including stereotypies. Brain imaging show thin corpus callosum, generalized atrophy, and mild periventricular gliosis.
Intellectual developmental disorder with short stature and behavioral abnormalities
An autosomal recessive disorder with onset in infancy and characterized by intellectual disability, developmental delay, short stature, aphasia, and hypotonia. Additional features include seizures and behavioral abnormalities, such as inattention, hyperactivity and aggression.
Intellectual developmental disorder with short stature and variable skeletal anomalies
An autosomal recessive disorder characterized by severe intellectual disability, speech and language impairment, developmental delay, and cardiac, thyroid and skeletal abnormalities. Skeletal features include short stature, camptodactyly, fifth finger clinodactyly, thumb hypoplasia, overlapping toes, and kyphosis or lumbar vertebral abnormalities.
Intellectual developmental disorder with short stature, facial anomalies, and speech defects
An autosomal recessive disorder characterized by global developmental delay, mildly to severely impaired intellectual development, delayed or slurred speech, and short stature. Dysmorphic features included a large bulbous nose and variable microretrognathia. Some patients show joint hyperlaxity and dislocations.
Intellectual developmental disorder with speech delay and axonal peripheral neuropathy
An autosomal recessive disorder characterized by mild global developmental delay, mild to moderate intellectual disability, motor impairment, unsteady or ataxic gait, and severe speech delay apparent in the first years of life. Signs of a peripheral axonal neuropathy, including progressive distal muscle weakness and atrophy of the lower limbs, foot and hand deformities, and dysarthria, are observed in most patients. Some patients may have autistic features or attention deficit-hyperactivity disorder.
Intellectual developmental disorder with speech delay and dysmorphic facies
An autosomal dominant disorder characterized by mild to severe intellectual disability, global developmental delay, mild but distinct facial dysmorphism, fifth finger clinodactyly, and small stature. Hypotonia, ventricular septal defect, and spastic quadriparesis may also be present.
Intellectual developmental disorder with speech delay, autism and dysmorphic facies
An autosomal dominant disorder characterized by mild to severe intellectual disability, developmental delay, delayed or absent speech, hypotonia, short stature, autistic features, and highly variable dysmorphic facial features.
Intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities
An autosomal dominant developmental disorder with onset in first months of life, and characterized by delayed psychomotor development with intellectual disability and speech delay. Additional features include autistic features, attention deficit-hyperactivity disorder, anxiety, and other behavioral abnormalities. Some patients suffer from recurrent infections, asthma and allergies.
Intellectual developmental disorder, autosomal dominant 1
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Intellectual developmental disorder, autosomal dominant 10
Intellectual developmental disorder, autosomal dominant 11
Intellectual developmental disorder, autosomal dominant 13
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD13 is associated with variable neuronal migration defects and mild dysmorphic features. Some patients may also show signs of peripheral neuropathy, such as abnormal gait and hyporeflexia.
Intellectual developmental disorder, autosomal dominant 2
Intellectual developmental disorder, autosomal dominant 21
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD21 features include short stature, microcephaly, and developmental delay.
Intellectual developmental disorder, autosomal dominant 22
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD22 patients have limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures.
Intellectual developmental disorder, autosomal dominant 23
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD23 patients manifest moderate to severe intellectual disability with additional variable features of brachycephaly, a low hairline, depressed nasal bridge, prominent high nasal root, tubular nose, upslanting palpebral fissures, long and smooth philtrum, micrognathia, thin upper lip, and crowded teeth. Behavioral problems, including obsessive-compulsive disorder, hand flapping with ritualized behavior, and autism, are prominent features.
Intellectual developmental disorder, autosomal dominant 26
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD26 features include autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms.
Intellectual developmental disorder, autosomal dominant 29
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD29 patients manifest severe intellectual disability, behavioral difficulties, speech and motor delays, and dysmorphic facial features.
Intellectual developmental disorder, autosomal dominant 3
Intellectual developmental disorder, autosomal dominant 30, with speech delay and behavioral abnormalities
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD30 patients manifest intellectual disability, speech delay, and subtle facial dysmorphisms, including hypertelorism, ptosis, and a wide mouth. Behavioral abnormalities, including attention-deficit hyperactivity disorder, autistic features, and aggression are commonly observed.
Intellectual developmental disorder, autosomal dominant 33
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD33 patients manifest microcephaly in addition to intellectual disability.
Intellectual developmental disorder, autosomal dominant 34
Intellectual developmental disorder, autosomal dominant 35
Intellectual developmental disorder, autosomal dominant 36
Intellectual developmental disorder, autosomal dominant 38
Psychomotor retardation, epilepsy, and language disability syndrome
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD38 common features are severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly.
Intellectual developmental disorder, autosomal dominant 39
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD39 patients show delayed psychomotor development and autistic features.
Intellectual developmental disorder, autosomal dominant 4
Intellectual developmental disorder, autosomal dominant 40
Intellectual developmental disorder, autosomal dominant 41
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD41 patients manifest delayed psychomotor development, variable severity of intellectual disability, and delayed language. Non-specific dysmorphic features and autistic behavior is observed in some patients.
Intellectual developmental disorder, autosomal dominant 42
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD42 patients manifest global developmental delay commonly accompanied by hypotonia, seizures of various types, ophthalmological manifestations, and poor growth.
Intellectual developmental disorder, autosomal dominant 43
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD43 patients manifest developmental delay, intellectual disability, hypotonia, and dysmorphic features.
Intellectual developmental disorder, autosomal dominant 44, with microcephaly
A disorder characterized by developmental delay, variable intellectual disability, distinctive facial features, and abnormalities of the fingers. Most patients also have microcephaly.
Intellectual developmental disorder, autosomal dominant 45
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD45 patients manifest developmental delay, variable intellectual disability, and behavioral disorders, including autistic features, attention deficit, and hyperactivity.
Intellectual developmental disorder, autosomal dominant 46
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD46 patients manifest developmental delay and mild to moderate intellectual disability.
Intellectual developmental disorder, autosomal dominant 47
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD47 patients manifest developmental delay and mild to moderate intellectual disability, usually with delayed speech.
Intellectual developmental disorder, autosomal dominant 48
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD48 patients manifest global developmental delay and moderate to severe intellectual disability.
Intellectual developmental disorder, autosomal dominant 5
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD5 patients show global developmental delay with delayed motor development, hypotonia, moderate-to-severe intellectual disability, and severe language impairment. Epilepsy and autism can be present in some patients.
Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities
Intellectual developmental disorder, autosomal dominant 51
Intellectual developmental disorder, autosomal dominant 52
Intellectual developmental disorder, autosomal dominant 53
Intellectual developmental disorder, autosomal dominant 54
Intellectual developmental disorder, autosomal dominant 55, with seizures
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD55 patients suffer from seizures appearing during the first years of life.
Intellectual developmental disorder, autosomal dominant 56
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Intellectual developmental disorder, autosomal dominant 57
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD57 is characterized by delayed psychomotor development apparent in infancy or early childhood, and a variety of behavioral abnormalities. Affected individuals may have severe gastro-intestinal problems, and facial dysmorphism.
Intellectual developmental disorder, autosomal dominant 58
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD58 patients show delayed development, intellectual disability, language delay and speech impairment. Some patients have motor delay or incoordination, and minor dysmorphic features.
Intellectual developmental disorder, autosomal dominant 59
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Intellectual developmental disorder, autosomal dominant 6, with or without seizures
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD6 additional features may include seizures, hypotonia, abnormal movements, such as dystonia, and autistic features.
Intellectual developmental disorder, autosomal dominant 60, with seizures
An autosomal dominant disorder characterized by global developmental delay apparent in the first six months of life, followed by onset of seizures between 21 months and 4 years. Disease features include moderate-to-severe intellectual disability, poor speech, delayed walking, and ataxia.
Intellectual developmental disorder, autosomal dominant 61
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD61 is characterized by global developmental delay apparent in infancy with mildly impaired intellectual development, expressive speech delay, and behavioral abnormalities, including autism spectrum disorder and attention deficit-hyperactivity disorder. Additional features are highly variable and may include non-specific dysmorphic features, obstipation, ocular anomalies, and poor overall growth.
Intellectual developmental disorder, autosomal dominant 62
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development.
Intellectual developmental disorder, autosomal dominant 63, with macrocephaly
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD63 is characterized by moderate to severe impaired intellectual development with poor or absent speech, global developmental delay, and variable behavioral abnormalities. Variable dysmorphic features are preset in half of the patients.
Intellectual developmental disorder, autosomal dominant 64
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD64 is characterized by mildly to severely impaired intellectual development, speech delay, and autism spectrum disorder in most patients. Additional variable features may include motor delay, attention deficit-hyperactivity disorder, and non-specific dysmorphic features.
Intellectual developmental disorder, autosomal dominant 65
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD65 is characterized by delayed motor and speech acquisition, variably impaired intellectual development, behavioral abnormalities, and dysmorphic facial features. Additional variable features include feeding difficulties, hypotonia, and seizures.
Intellectual developmental disorder, autosomal dominant 66
An autosomal dominant disorder characterized by mild to moderate global development delay, impaired intellectual development, and speech delay. Additional common symptoms include autism, seizures, and distal limb abnormalities. Disease severity is highly variable.
Intellectual developmental disorder, autosomal dominant 67
An autosomal dominant disorder characterized by global development delay and impaired intellectual development apparent from infancy or early childhood. Additional features may include behavioral abnormalities, and language and sleeping difficulties.
Intellectual developmental disorder, autosomal dominant 68
An autosomal dominant disorder characterized by developmental delay, intellectual disability, microcephaly, poor growth, feeding difficulties, and dysmorphic features. Some patients may have autism spectrum disorder or attention deficit-hyperactivity disorder.
Intellectual developmental disorder, autosomal dominant 69
An autosomal dominant disorder characterized by developmental delay and variably impaired intellectual development. Additional features may include intention tremor in infancy and seizures in childhood, with remission of these in adolescence.
Intellectual developmental disorder, autosomal dominant 7
A disease characterized by primary microcephaly, severe intellectual disability without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Intellectual disability is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Intellectual developmental disorder, autosomal dominant 70
An autosomal dominant disorder characterized by mild global developmental delay, moderately impaired intellectual disability with speech difficulties, and behavioral abnormalities.
Intellectual developmental disorder, autosomal recessive 1
Intellectual developmental disorder, autosomal recessive 12
Intellectual developmental disorder, autosomal recessive 13
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Brain magnetic resonance imaging of MRT13 patients indicates the presence of mild cerebral white matter hypoplasia. Microcephaly is present in some but not all affected individuals.
Intellectual developmental disorder, autosomal recessive 14
Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy
Intellectual developmental disorder, autosomal recessive 18
Intellectual developmental disorder, autosomal recessive 2
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features.
Intellectual developmental disorder, autosomal recessive 27
Intellectual developmental disorder, autosomal recessive 3
Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly
A disorder characterized by mild to moderate intellectual disability, megalencephaly or enlarged head circumference, and a mild variant of lissencephaly with anterior-predominant pachygyria with shallow and unusually wide sulci and mildly thickened cortex. Some patients may have seizures.
Intellectual developmental disorder, autosomal recessive 37
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT37 patients manifest delayed global development with speech delay, hypotonia, spasticity, and a sleep disorder. Severe behavioral abnormalities include aggression, hyperactivity, and grinding of the teeth.
Intellectual developmental disorder, autosomal recessive 38
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT38 is characterized by global developmental delay affecting motor, speech, adaptive, and social development. Patients manifest autistic features, aggression, self-injury, impulsivity, and distractibility.
Intellectual developmental disorder, autosomal recessive 39
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT39 affected individuals show delayed psychomotor development, severe speech delay, short stature, kyphoscoliosis, and dysmorphic facial features. Behavioral abnormalities include hyperactivity, aggression, and stereotypic movements.
Intellectual developmental disorder, autosomal recessive 41
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT41 most consistent features are global developmental delay, macrocephaly with frontal bossing, high levels of anxiety, and some features suggestive of a pervasive developmental disorder. Less common features include fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly.
Intellectual developmental disorder, autosomal recessive 43
Intellectual developmental disorder, autosomal recessive 44
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT44 manifestations include mild to severe cognitive impairment, delayed psychomotor development, seizures in some patients, and dysmorphic features.
Intellectual developmental disorder, autosomal recessive 45
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT45 manifestations include mild to moderate intellectual disability and dysmorphic features, including coarse facies, broad nasal bridge, fleshy nares, and thick, prominent lips.
Intellectual developmental disorder, autosomal recessive 46
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT46 manifestations include delayed psychomotor development apparent from infancy or early childhood, delayed or absent expressive speech, hypotonia, and therapy-responsive seizures in some patients. Behavioral abnormalities are variable and include aggression, self-injurious behavior, and sleep disturbances.
Intellectual developmental disorder, autosomal recessive 47
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT47 patients show delayed development, with cognition and speech more affected than motor skills.
Intellectual developmental disorder, autosomal recessive 48
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT48 patients show moderate to severe intellectual disability and additional features including progressive tremor, speech impairment, and sometimes behavioral problems.
Intellectual developmental disorder, autosomal recessive 5
Intellectual developmental disorder, autosomal recessive 50
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT50 patients show mild intellectual disability and microcephaly.
Intellectual developmental disorder, autosomal recessive 51
Intellectual developmental disorder, autosomal recessive 52
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT52 clinical features include global developmental delay, severe intellectual disability with poor speech, and mild seizures in early childhood.
Intellectual developmental disorder, autosomal recessive 54
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity.
Intellectual developmental disorder, autosomal recessive 56
Intellectual developmental disorder, autosomal recessive 57
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT57 patients have moderate to severe intellectual disability, and delayed psychomotor development with poor or absent speech. Some patients manifest seizures and autistic features.
Intellectual developmental disorder, autosomal recessive 58
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT58 transmission pattern is consistent with autosomal recessive inheritance.
Intellectual developmental disorder, autosomal recessive 59
Intellectual developmental disorder, autosomal recessive 6
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT6 patients display mild to severe intellectual disability and psychomotor development delay in early childhood. Patients do not have neurologic problems, congenital malformations, or facial dysmorphism. Body height, weight, and head circumference are normal.
Intellectual developmental disorder, autosomal recessive 60
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT60 patients display mild intellectual disability, delayed psychomotor development, learning difficulties, and poor overall growth with variable microcephaly.
Intellectual developmental disorder, autosomal recessive 61
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT61 patients manifest delayed psychomotor development, moderate to severe intellectual disability, and variable dysmorphic facial features. Refractory seizures and brain abnormalities are present in severely affected patients.
Intellectual developmental disorder, autosomal recessive 63
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT63 patients manifest global developmental delay, severe intellectual disability, and seizures.
Intellectual developmental disorder, autosomal recessive 64
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT64 patients have moderate to severe intellectual disability, delayed motor development, aggressive behavior, and slurred or absent speech.
Intellectual developmental disorder, autosomal recessive 65
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT65 patients have moderate to severe intellectual disability, developmental delay, and facial dysmorphism. Camptodactyly is present in some patients.
Intellectual developmental disorder, autosomal recessive 66
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT66 patients have intellectual disability, delayed speech development, neuropsychiatric symptoms, and relatively normal life span.
Intellectual developmental disorder, autosomal recessive 67
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Some MRT67 patients manifest seizures and sensorineural hearing loss.
Intellectual developmental disorder, autosomal recessive 68
Intellectual developmental disorder, autosomal recessive 69
Intellectual developmental disorder, autosomal recessive 7
Intellectual developmental disorder, autosomal recessive 70
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT70 patients manifest impaired intellectual development, mild facial dysmorphism, febrile seizures, and behavioral abnormalities.
Intellectual developmental disorder, autosomal recessive 71
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT71 features include impaired intellectual development, global developmental delay, mildly delayed walking, poor language, seizures in the first years of life, and behavioral abnormalities.
Intellectual developmental disorder, autosomal recessive 72
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT72 patients manifest moderate to severe intellectual disability, microcephaly, and dysmorphic facial features.
Intellectual developmental disorder, autosomal recessive 73
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT73 patients manifest global developmental delay with hypotonia and mildly delayed walking, impaired intellectual development with poor or absent speech, and mildly dysmorphic features.
Intellectual developmental disorder, autosomal recessive 74
A disorder characterized by intellectual impairment, macrocephaly, and dysmorphic features. Epilepsy with eyelid myoclonus has also been reported.
Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly
An autosomal recessive disorder characterized by global developmental delay apparent from infancy or early childhood, impaired intellectual development, and behavioral and psychiatric abnormalities. Some patients present seizures and facial dysmorphism. Brain imaging often shows cortical anomalies.
Intellectual developmental disorder, autosomal recessive 76
An autosomal recessive disorder characterized by global developmental delay, severely impaired intellectual development, absent speech, seizures, sleep disturbances, and feeding difficulties.
Intellectual developmental disorder, autosomal recessive 77
An autosomal recessive neurodevelopmental disorder apparent from infancy and characterized by global developmental delay, variably impaired cognitive development, delayed walking, and poor speech in some cases.
Intellectual developmental disorder, FRA12A type
Intellectual developmental disorder, autosomal dominant, FRA12A type
An autosomal dominant disorder characterized by impaired intellectual development with or without other anomalies, in association with a folate-sensitive chromosomal fragile site at 12q13. Main features are global developmental delay, significant learning disability, epileptic seizures, and behavioral problems. The disorder can be inherited without phenotypic effects.
Intellectual developmental disorder, X-linked 1
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations.
Intellectual developmental disorder, X-linked 100
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID100 clinical features include intellectual disability, epilepsy, microcephaly and cortical malformations.
Intellectual developmental disorder, X-linked 101
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID101 clinical features include global developmental delay, hyperactivity often with aggressive outbursts, and seizures in some patients. Several affected individuals have long face, prominent ears, and squint or strabismus.
Intellectual developmental disorder, X-linked 103
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations.
Intellectual developmental disorder, X-linked 104
Intellectual developmental disorder, X-linked 105
Intellectual developmental disorder, X-linked 106
Intellectual developmental disorder, X-linked 107
Intellectual developmental disorder, X-linked 108
Intellectual developmental disorder, X-linked 109
A form of mild to moderate intellectual disability associated with learning difficulties, communication deficits, attention problems, hyperactivity, and autistic behavior. It is associated with a fragile site on chromosome Xq28. Intellectual disability is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Intellectual developmental disorder, X-linked 110
Intellectual developmental disorder, X-linked 12
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID12 patients manifest variable degrees of intellectual disability. Commonly observed features included speech delay, elevated BMI, short stature, seizure disorders, gait disturbance, and tremors.
Intellectual developmental disorder, X-linked 19
Intellectual developmental disorder, X-linked 21
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic intellectual disability presents with associated physical, neurological and/or psychiatric manifestations.
Intellectual developmental disorder, X-linked 29
Intellectual developmental disorder, X-linked 30
Intellectual developmental disorder, X-linked 41
Intellectual developmental disorder, X-linked 45
Intellectual developmental disorder, X-linked 46
Intellectual developmental disorder, X-linked 50
Intellectual developmental disorder, X-linked 58
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked intellectual disability, while syndromic intellectual disability presents with associated physical, neurological and/or psychiatric manifestations.
Intellectual developmental disorder, X-linked 63
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked intellectual disability, while syndromic forms presents with associated physical, neurological and/or psychiatric manifestations.
Intellectual developmental disorder, X-linked 72
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID72 patients can manifest autism spectrum disorder, seizures and macrocephaly as additional features.
Intellectual developmental disorder, X-linked 88
Intellectual developmental disorder, X-linked 89
Intellectual developmental disorder, X-linked 9
Intellectual developmental disorder, X-linked 90
Intellectual developmental disorder, X-linked 91
Intellectual developmental disorder, X-linked 92
Intellectual developmental disorder, X-linked 93
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. XLID93 is associated with macrocephaly.
Intellectual developmental disorder, X-linked 95
Intellectual developmental disorder, X-linked 96
Intellectual developmental disorder, X-linked 97
Intellectual developmental disorder, X-linked 98
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. XLID98 patients show delayed psychomotor development, absent or poor speech development, and postnatal growth retardation, often with microcephaly. Some patients show autistic behavioral features, such as stereotypic hand movements and repetitive behaviors. Additional, more variable features include spasticity, axial hypotonia, seizures, drooling, gastroesophageal reflux, and lack of sphincter control.
Intellectual developmental disorder, X-linked 99
Intellectual developmental disorder, X-linked 99, syndromic, female-restricted
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning, associated with impairments in adaptive behavior and manifested during the developmental period. MRXS99F affected females manifest intellectual disability, developmental delay, facial dysmorphism, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Inheritance is X-linked dominant.
Intellectual developmental disorder, X-linked, syndromic 11
Intellectual developmental disorder, syndromic 11, Shashi type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS11 patients manifest moderate intellectual disability and craniofacial dysmorphism.
Intellectual developmental disorder, X-linked, syndromic 13
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS13 patients manifest intellectual disability associated with other variable features such as spasticity, episodes of manic depressive psychosis, increased tone and macroorchidism.
Intellectual developmental disorder, X-linked, syndromic 14
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS14 patients manifest intellectual disability associated with other variable signs such as autistic features, slender build, poor musculature, long, thin face, high-arched palate, high nasal bridge, and pectus deformities.
Intellectual developmental disorder, X-linked, syndromic 28
Agenesis of the corpus callosum with impaired intellectual development, ocular coloboma and micrognathia
An intellectual disability syndrome characterized by agenesis of the corpus callosum, coloboma of the iris and optic nerve, severe retrognathia, and intellectual deficit. Intellectual disability is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Intellectual developmental disorder, X-linked, syndromic 32
A syndrome characterized by profound intellectual deficit, delayed psychomotor development beginning in infancy and little or no speech development. Additional features include seizures, large joint contractures, and abnormal positioning of the thumbs.
Intellectual developmental disorder, X-linked, syndromic 33
A syndrome characterized by intellectual deficit, delayed psychomotor development, delayed speech and language, and characteristic facial features.
Intellectual developmental disorder, X-linked, syndromic 34
A syndrome characterized by intellectual deficit, delayed psychomotor development, poor speech, and dysmorphic features.
Intellectual developmental disorder, X-linked, syndromic 35
Intellectual developmental disorder, X-linked, syndromic, Armfield type
An X-linked recessive disorder characterized by global developmental delay with impaired intellectual development, walking difficulties and poor or absent speech. Affected individuals display a distinctive phenotype characterized by postnatal growth retardation, variable head circumference with a prominent forehead and dysmorphic facial features, ocular abnormalities, and seizures.
Intellectual developmental disorder, X-linked, syndromic, Bain type
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSB patients manifest developmental delay, intellectual disability, autism, hypotonia, seizures, and dysmorphic facial features. Only females are affected.
Intellectual developmental disorder, X-linked, syndromic, Billuart type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSBL patients manifest intellectual disability associated with cerebellar hypoplasia and distinctive facial dysmorphism.
Intellectual developmental disorder, X-linked, syndromic, Cabezas type
Intellectual deficit, X-linked, Cabezas type
A syndromic form of X-linked intellectual disability characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span.
Intellectual developmental disorder, X-linked, syndromic, Christianson type
A syndrome characterized by profound intellectual disability, epilepsy, ataxia, and microcephaly. It shows phenotypic overlap with Angelman syndrome.
Intellectual developmental disorder, X-linked, syndromic, Claes-Jensen type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSCJ patients manifest intellectual disability associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism.
Intellectual developmental disorder, X-linked, syndromic, Hackman-Di Donato type
An X-linked recessive disorder characterized by impaired intellectual development, global developmental delay, hypotonia, joint contractures, behavioral abnormalities, Marfanoid habitus, scoliosis, and mildly dysmorphic facies.
Intellectual developmental disorder, X-linked, syndromic, Hedera type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSH patients manifest mild to moderate intellectual disability associated with epilepsy, delays in motor milestones and speech acquisition in infancy.
Intellectual developmental disorder, X-linked, syndromic, Houge type
A disorder characterized by delayed development, intellectual disability, speech and language delay, and early-onset seizures. Carrier females may be mildly affected.
Intellectual developmental disorder, X-linked, syndromic, Lubs type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSL patients manifest intellectual disability associated with variable features. They include swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections, hypotonia, mild myopathy and characteristic facies such as downslanting palpebral fissures, hypertelorism and a short nose with a low nasal bridge.
Intellectual developmental disorder, X-linked, syndromic, Lujan-Fryns type
A disorder characterized by tall stature with asthenic habitus, macrocephaly, a tall narrow face, maxillary hypoplasia, a high narrow palate with dental crowding, a small or receding chin, long hands with hyperextensible digits, hypernasal speech, hypotonia, mild-to-moderate intellectual disability, behavioral aberrations and dysgenesis of the corpus callosum.
Intellectual developmental disorder, X-linked, syndromic, Nascimento-type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSN features include dysmorphic facies, hirsutism, skin and nails abnormalities, obesity, speech anomalies and seizures.
Intellectual developmental disorder, X-linked, syndromic, Pilorge type
A disorder characterized by global developmental delay with variably impaired intellectual development, speech delay, and behavioral abnormalities. Variable features include motor incoordination, seizures, and ocular abnormalities. Disease onset is in infancy, and severity is higly variable.
Intellectual developmental disorder, X-linked, syndromic, Raymond type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Some MRXSR patients show additional features, including marfanoid habitus, epilepsy, facial dysmorphism, hypotonia, and behavioral problems.
Intellectual developmental disorder, X-linked, syndromic, Siderius type
A syndrome characterized by mild to borderline intellectual disability with or without cleft lip/cleft palate.
Intellectual developmental disorder, X-linked, syndromic, Snijders Blok type
A disorder characterized by mild to severe intellectual disability, hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Additionally, patients manifest variable non-neurologic features such as joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, and precocious puberty.
Intellectual developmental disorder, X-linked, syndromic, Snyder-Robinson type
An X-linked intellectual disability syndrome characterized by a collection of clinical features including facial asymmetry, marfanoid habitus, hypertonia, osteoporosis and unsteady gait.
Intellectual developmental disorder, X-linked, syndromic, Stocco dos Santos type
Intellectual deficit X-linked Stocco Dos Santos type
A syndrome characterized by severe intellectual disability with hyperactivity, aggressive behavior, delayed or no speech, and seizures. Additional features include congenital bilateral hip luxation, short stature, and kyphosis.
Intellectual developmental disorder, X-linked, syndromic, Turner type
An X-linked neurodevelopmental disorder with highly variable clinical manifestations. Common features consist of moderate to profound intellectual disability, delayed or absent speech, short stature with small hands and feet, and non-specific but recurrent dysmorphic facial features such as macrocephaly, microcephaly, a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures and a short philtrum. Patients may manifest other features, such as hypotonia, seizures and delayed bone age.
Intellectual developmental disorder, X-linked, syndromic, Wilson-Turner type
A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males.
Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies
A disorder characterized by severe developmental delay with impaired intellectual development and poor speech, coarse facial dysmorphisms, and Blaschkoid pigmentary mosaicism. Additional clinical features may include epilepsy, orthopedic abnormalities, hypotonia, and growth abnormalities. The disorder affects both males and females.
Intellectual developmental disorder, X-linked, syndromic, Wu type
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSW patients have moderate intellectual disability, and additional variable features such as macrocephaly, seizures, myoclonic jerks, autistic behavior, asthenic body habitus, distal muscle weakness and hyporeflexia.
Intellectual developmental disorder, X-linked, with isolated growth hormone deficiency
Intellectual developmental disorder, X-linked, with panhypopituitarism
A disorder characterized by the association of variable degrees of intellectual disability with panhypopituitarism, variable combinations of hypothyroidism, delayed pubertal development, and short stature due to growth hormone deficiency.
Intellectual disability and myopathy syndrome
An autosomal recessive disorder characterized by global developmental delay, mildly impaired intellectual development, hypotonia, muscle weakness and fatigue, and white matter abnormalities on brain imaging. Variable additional features may include sensorineural hearing loss, dysmorphic facies, and progressive heart disease.
Intellectual disability-hypotonic facies syndrome, X-linked, 1
Intellectual disability X-linked with growth retardation deafness and microgenitalism
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSHF1 features include severe intellectual disability, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.
Interleukin 1 receptor antagonist deficiency
Autoinflammatory disease due to interleukin-1 receptor antagonist deficiency
A rare autoinflammatory disease of skin and bone resulting in sterile multifocal osteomyelitis, periostitis, and pustulosis from birth. The term autoinflammatory disease describes a group of disorders characterized by attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T-cells.
Pulmonary alveolar proteinosis, Reunion island
An autosomal recessive, life-threatening disorder characterized by respiratory insufficiency and progressive liver disease with onset in infancy or early childhood. Clinical features include failure to thrive, hypotonia, intermittent lactic acidosis, aminoaciduria, hypothyroidism, interstitial lung disease, pulmonary alveolar proteinosis, anemia, and liver canalicular cholestasis, steatosis, and iron deposition.
A form of interstitial lung disease, a heterogeneous group of diseases affecting the distal part of the lung and characterized by a progressive remodeling of the alveolar interstitium. The disease spectrum ranges from idiopathic interstitial pneumonia or pneumonitis to idiopathic pulmonary fibrosis, that is associated with an increased risk of developing lung cancer. Clinical features of interstitial lung disease include dyspnea, clubbing of the fingers, and restrictive lung capacity. ILD1 inheritance can be autosomal dominant with incomplete penetrance, and autosomal recessive.
A form of interstitial lung disease, a heterogeneous group of diseases affecting the distal part of the lung and characterized by a progressive remodeling of the alveolar interstitium. The disease spectrum ranges from idiopathic interstitial pneumonia or pneumonitis to idiopathic pulmonary fibrosis, that is associated with an increased risk of developing lung cancer. Clinical features of interstitial lung disease include dyspnea, clubbing of the fingers, and restrictive lung capacity. ILD2 inheritance is autosomal dominant.
Karyomegalic tubulointerstitial nephritis
A rare kidney disease characterized by chronic tubulointerstitial nephritis associated with massively enlarged tubular epithelial cell nuclei. The clinical picture is associated with recurrent upper respiratory tract infections in addition to chronic kidney disease beginning in the third decade of life.
A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain.
A yellow, well-differentiated, circumscribed tumor that arises from enterochromaffin cells in the small intestine or, less frequently, in other parts of the gastrointestinal tract.
An autosomal recessive disorder characterized by impaired intestinal peristalsis, recurrent episodes of haemorrhagic diarrhea, and distention of intestinal loops. Intestinal and hepatic portal venous gas, dysmorphic features, and developmental delay may also be present.
Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked
Congenital idiopathic intestinal pseudoobstruction
A disease characterized by a severe abnormality of gastrointestinal motility due to primary qualitative defects of enteric ganglia and nerve fibers. Affected individuals manifest recurrent signs of intestinal obstruction in the absence of any mechanical lesion.
A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.
Intractable childhood epilepsy with generalized tonic-clonic seizures
A disorder characterized by generalized tonic-clonic seizures beginning usually in infancy and induced by fever. Seizures are associated with subsequent mental decline, as well as ataxia or hypotonia. ICEGTC is similar to SMEI, except for the absence of myoclonic seizures.
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies
A rare condition characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis.
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency
An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth failure, metaphyseal dysplasia, adrenal hypoplasia congenita, growth hormone deficiency, genital anomalies, and immunodeficiency resulting in increased infections.
A disorder of iron homeostasis with incomplete and age-dependent penetrance. It is characterized by adult onset of increased hepatic and systemic iron levels, increased serum ferritin, normal or high transferrin saturation, and inappropriately low or normal levels of hepcidin. The severity of the phenotype depends on age, sex, as well as additional genetic or acquired factors including alcohol consumption and increased body weight.
Hypochromic microcytic anemia with defect in iron metabolism
Key features include congenital hypochromic microcytic anemia, very low mean corpuscular erythrocyte volume, low transferrin saturation, abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron, and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron.
A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension
Patella aplasia, coxa vara, and tarsal synostosis
An autosomal dominant bone disease characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami.
Deficiency of acyl-CoA dehydrogenase family member 8
An autosomal recessive metabolic disorder characterized by plasma carnitine deficiency and elevated C4-acylcarnitine. Patients manifest variable clinical features including failure to thrive, seizures, anemia, muscular hypotonia and developmental delay. Some patients may be asymptomatic.
Isovaleric acid CoA dehydrogenase deficiency
A metabolic disorder characterized by retarded psychomotor development, a peculiar odor resembling sweaty feet, an aversion to dietary protein, and pernicious vomiting, leading to acidosis and coma. The acute neonatal form leads to massive metabolic acidosis from the first days of life and rapid death.
Radial ray defects, hearing impairment, external ophthalmoplegia, and thrombocytopenia
An autosomal dominant condition characterized by upper limbs anomalies (radial ray defects, carpal bones fusion), extraocular motor disturbances, congenital bilateral non-progressive mixed hearing loss. Other less consistent malformations include heart involvement, mild thrombocytopenia and leukocytosis (before age 50), shoulder girdle hypoplasia, imperforate anus, kidney malrotation or rectovaginal fistula. The IVIC syndrome is an allelic disorder of Duane-radial ray syndrome with a similar phenotype.
An autosomal recessive disorder characterized by developmental delay and intellectual disability. Additional variable features include ataxic gait and abnormal movements, visual impairment, microcephaly, abnormal foot or hand posturing, kyphoscoliosis, dysmorphic facial features or seizures. Brain imaging typically shows cerebellar atrophy and hypoplasia of the corpus callosum.
Craniosynostosis-midfacial hypoplasia-foot abnormalities
An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.
Cone-rod dystrophy and amelogenesis imperfecta
A syndrome characterized by the association of cone-rod dystrophy and amelogenesis imperfecta.
Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold
An autosomal dominant neurodevelopmental disorder characterized by mild to severe intellectual disability, psychomotor developmental delay, speech delay, and behavioral manifestations including attention deficit-hyperactivity disorder, autism and anxiety disorders. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold, hypersensitivity to sound, hypotonia, broad-based gait, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet.
A syndrome characterized by congenital microcephaly, moderately severe intellectual disability, and symmetrical digital anomalies. Digital malformations of variable degree include hallux valgus, syndactyly of toes 4 and 5, short fifth fingers, single flexion crease of fifth fingers, polydactyly and synpolydactyly.
Cardioauditory syndrome of Jervell and Lange-Nielsen
Congenital deafness and functional heart disease
Prolonged QT interval in EKG and sudden death
An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death.
This disorder includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and intellectual disability. Pancreas of individuals with JBS do not express UBR1 and show intrauterine-onset destructive pancreatitis.
An autosomal recessive disease characterized by generalized joint laxity, joint dislocation, pectus carinatum, short stature, and severe myopia with retinal detachment.
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease.
An autosomal recessive disorder characterized by severe intellectual disability, hypotonia, breathing abnormalities in infancy, and dysmorphic facial features. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include renal disease, abnormal eye movements, and postaxial polydactyly.
An autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis and polydactyly.
An autosomal recessive disorder characterized by oculomotor apraxia, variable coloboma, and rare kidney involvement. Neuroradiologically, it is characterized by an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and polydactyly.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. JBTS18 patients have vermis agenesis and the molar tooth sign as well as severe kyphoscoliosis. Other features include intrauterine growth retardation, oral anomalies, micrognathism, polydactyly and camptodactyly, joint laxity, horseshoe kidney, and ventricular septal defect.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). JBTS19 patients have polycystic kidney disease, Leber congenital amaurosis, cerebellar vermis hypoplasia, and breathing abnormality.
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly.
A mild form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS25 clinical manifestations appear to be confined to the neurologic system. JBTS25 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS26 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS27 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS28 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS29 inheritance is autosomal recessive.
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 3 shows minimal extra central nervous system involvement and appears not to be associated with renal dysfunction.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS30 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS31 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS32 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS33 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS34 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS35 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS36 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS37 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS38 inheritance is autosomal recessive.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS39 inheritance is autosomal recessive.
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 4 is a phenotypically mild form.
A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS40 inheritance is autosomal recessive.
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis.
Cleft Lip/Palate with abnormal thumbs and microcephaly
Cleft lip/palate with radial head and digital anomalies
An autosomal recessive syndrome characterized by cleft lip/palate, microcephaly, ptosis, hypoplasia or aplasia of thumbs, short stature, dislocation of radial head, and fusion of humerus and radius leading to elbow restriction.
Susceptibility to juvenile absence epilepsy 1
A subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures.
Susceptibility to juvenile absence epilepsy 2
A rare, familial form of juvenile arthritis characterized by autosomal recessive inheritance and onset in early childhood of symmetric, chronic joint inflammation. It causes joint swelling, pain, stiffness and restricted joint movement. JUVAR has high clinical variability. Some patients exhibit systemic symptoms, including quotidian fever, erythematous rash, generalized lymphadenopathy, hepatomegaly, and/or splenomegaly. Others display polyarthritis without systemic inflammation.
Susceptibility to juvenile myoclonic epilepsy 1
A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.
A form of juvenile myoclonic epilepsy, a subtype of idiopathic generalized epilepsy generally characterized by afebrile seizures with onset in adolescence (rather than in childhood) and myoclonic jerks, which usually occur after awakening and are triggered by sleep deprivation and fatigue. EJM10 is an autosomal dominant seizure disorder with variable manifestations, even within families. Affected individuals have febrile, myoclonic, tonic-clonic, or absence seizures, although several seizure types can occur in the same individual. Some patients have onset of seizures in the first years of life.
Susceptibility to juvenile myoclonic epilepsy 5
Susceptibility to juvenile myoclonic epilepsy 6
Susceptibility to juvenile myoclonic epilepsy 7
Susceptibility to juvenile myoclonic epilepsy 8
Autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers.
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome
JP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic etiology of this association is unknown.
A neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons while the lower neurons are unaffected.
An autosomal dominant, congenital syndrome characterized by intellectual disability and additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.
A congenital intellectual disability syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy.
An autosomal recessive neurodevelopmental disorder characterized by intellectual disability, cataracts, coloboma, kyphosis, and coarse facial features.
Autosomal recessive disorder characterized by late-onset, angiokeratoma corporis diffusum and mild intellectual impairment.
Dextrocardia-bronchiectasis-sinusitis syndrome
Primary ciliary dyskinesia Kartagener type
An autosomal recessive disorder characterized by the association of primary ciliary dyskinesia with situs inversus. Clinical features include recurrent respiratory infections, bronchiectasis, infertility, and lateral transposition of the viscera of the thorax and abdomen. The situs inversus is most often total, although it can be partial in some cases (isolated dextrocardia or isolated transposition of abdominal viscera).
Blepharophimosis-ptosis-intellectual disability syndrome
A syndrome characterized by blepharophimosis, ptosis, mild upslanting of the palpebral fissures, epicanthus, ectodermal anomalies, developmental delay, and severe intellectual disability with absent speech. Proportionate growth retardation with a small head circumference/microcephaly, congenital malformations, muscular hypotonia, anomalies on brain imaging with hypoplasia of the corpus callosum, and low cholesterol levels are variably present.
An acute, self-limited vasculitis of infants and children characterized by prolonged fever unresponsive to antibiotics, polymorphous skin rash, erythema of the oral mucosa, lips, and tongue, erythema of the palms and soles, bilateral conjunctival injection, and cervical lymphadenopathy.
An autosomal recessive neurodevelopmental disorder characterized by impaired intellectual development, absent speech, hypotonia, profound developmental and motor delay with dystonia, poor coordination and spasticity, and visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy.
A syndrome characterized by macrodontia of the upper central incisors, distinctive craniofacial findings, short stature, skeletal anomalies, and neurologic involvement that includes global developmental delay, seizures, and intellectual disability.
An X-linked recessive syndrome characterized by craniofacial and digital abnormalities. Clinical features include a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and widening of all distal phalanges. Additional variable features are cognitive impairment and sensorineural deafness.
Kenny-Caffey syndrome autosomal recessive
An autosomal recessive form of Kenny-Caffey syndrome, a disorder characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. Clinical features include cortical thickening and medullary stenosis of the tubular bones, delayed closure of fontanels, defective dentition, small eyes with hypermetropia, and frontal bossing with a triangular face.
Dwarfism with cortical thickening of tubular bones and transient hypocalcemia
A disorder characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. Clinical features include cortical thickening and medullary stenosis of the tubular bones, delayed closure of fontanels, defective dentition, small eyes with hypermetropia, and frontal bossing with a triangular face.
A rare disease characterized by severe developmental delay, intellectual disability, severe generalized lipodystrophy, dysmorphic features including microcephaly, large prominent eyes, narrow nasal bridge, tented upper lip, high palate, open mouth, tightly adherent skin, and aged appearance.
Epidermal nevi of the common, non-organoid and non-epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood.
An ocular disorder characterized by corneal opacification, recurrent stromal keratitis and vascularization.
Keratitis-ichthyosis-deafness syndrome, autosomal dominant
An autosomal dominant form of keratitis-ichthyosis-deafness syndrome, a disease characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. Clinical features include deafness, ichthyosis, photophobia, absent or decreased eyebrows, sparse or absent scalp hair, decreased sweating and dysplastic finger and toenails.
Keratitis-ichthyosis-deafness syndrome, autosomal recessive
Ichthyosiform erythroderma, corneal involvement, and deafness
An autosomal recessive form of keratitis-ichthyosis-deafness syndrome, a disease characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. KIDAR patients manifest ichthyosis, failure to thrive and developmental delay in childhood, thrombocytopenia, photophobia, and progressive hearing loss. Low plasma copper and ceruloplasmin levels have been reported in some patients.
Frequent corneal dystrophy with an incidence that varies from 50 to 230 per 100'000. The cornea assumes a conical shape as a result of a progressive non-inflammatory thinning of the corneal stroma. Keratoconus is most often an isolated sporadic condition with cases of autosomal dominant and autosomal recessive transmission.
An autosomal dominant form of keratoconus, a common degenerative corneal disease characterized by progressive, non-inflammatory thinning of the corneal stroma, corneal ectasia, and cone-shaped corneal protrusion that results in reduced vision.
Keratoderma, palmoplantar, Bothnian type
A dermatological disorder characterized by diffuse non-epidermolytic hyperkeratosis of the skin of palms and soles. PPKB is frequently complicated by fungal infections.
Keratoderma, palmoplantar, epidermolytic
Keratosis palmaris et plantaris familiaris
A dermatological disorder characterized by diffuse thickening of the epidermis on the entire surface of palms and soles sharply bordered with erythematous margins. Some patients may present knuckle pads, thick pads of skin appearing over the proximal phalangeal joints.
Keratoderma, palmoplantar, Nagashima type
An autosomal recessive, non-syndromic, diffuse palmoplantar keratosis characterized by well-demarcated diffuse erythematous hyperkeratosis expanding onto the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis is mild and non-progressive.
Keratoderma, palmoplantar, non-epidermolytic
Nonepidermolytic palmoplantar keratoderma
A dermatological disorder characterized by well-demarcated hyperkeratosis is present over the palms and soles. A red band is frequently present at the periphery of the keratosis. It is usually non-transgredient, with a sharp demarcation of the lesions at the wrists.
Keratoderma, palmoplantar, non-epidermolytic, focal 1
Focal nonepidermolytic palmoplantar keratoderma
Keratoderma, focal nonepidermolytic palmoplantar
A dermatological disorder characterized by non-epidermolytic palmoplantar keratoderma limited to the pressure points on the balls of the feet, with later mild involvement on the palms. Oral, genital and follicular keratotic lesions are often present.
Keratodermia palmoplantaris papulosa Buschke-Fischer-Brauer type
Keratosis punctate palmoplantaris Buschke-Fisher-Brauer type
Punctate palmoplantar keratoderma type I
Punctate palmoplantar keratoderma type IA
An autosomal dominant dermatological disorder characterized by multiple hyperkeratotic, centrally indented, papules that develop in early adolescence, or later, and are irregularly distributed on the palms and soles (other palmoplantar keratoses have mostly diffuse hyperkeratinization). In mechanically irritated areas, confluent plaques can be found. Interfamilial and intrafamilial severity shows broad variation. In some cases, PPKP1 is associated with the development of early- and late-onset malignancies, including squamous cell carcinoma.
Keratoderma palmoplantar striate form II
A dermatological disorder characterized by thickening of the skin on the palms (linear pattern) and the soles (island-like pattern) and flexor aspect of the fingers. Abnormalities of the nails, the teeth and the hair are rarely present.
A dermatological disorder characterized by thickening of the stratum corneum and epidermal layers on palms and soles. There is no involvement of non-palmoplantar skin, and both hair and nails are normal.
Keratoderma, palmoplantar, with deafness
An autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness.
Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal
Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal
A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin.
Keratoderma-ichthyosis-deafness syndrome, autosomal recessive
An autosomal recessive disorder characterized by severe palmoplantar keratoderma, generalized ichthyosis, and sensorineural bilateral hearing loss. Additional variable features include contractures, mild bleeding diathesis, and psychomotor retardation.
An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age.
An autosomal dominant genodermatosis characterized by recurrent episodes of palmoplantar erythema and epidermal peeling presenting seasonal variation. KWE manifests during childhood. Skin lesions may spread to the dorsum of hands and feet and to the interdigital spaces. Lower legs, knees and thighs may also be involved. A less common finding is a slowly migratory, annular erythema that is seen mostly on the extremities. Between flares, the skin can appear unremarkable. Itching can occur, and hyperhidrosis, associated with a pungent odor, is invariably present. Formation of vesicles is rare, whereas keratolysis that causes the formation of dry blisters is regularly seen. Cold weather, moisture, febrile diseases, and physical and mental stress can trigger exacerbations. In severely affected individuals, skin manifestations persist unremittingly. Penetrance of the disease is high, but expressivity is variable, even within the same family.
Keratosis follicularis spinulosa decalvans X-linked
Keratosis follicularis spinulosa decalvans cum ophiasi
A rare disorder affecting the skin and the eye. Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration.
Keratosis linearis with ichthyosis congenita and sclerosing keratoderma
A keratinizing disorder characterized by ichthyosis, palmoplantar keratoderma with constricting bands around fingers, flexural deformities of fingers and keratotic papules in a linear distribution on the flexural side of large joints. Histological examination of the skin of affected individuals shows hypertrophy and hyperplasia of the spinous, granular and horny epidermal layer.
A group of rare genodermatoses characterized by keratotic follicular papules, variable degrees of inflammation, and secondary atrophic scarring. Most cases are associated with an atopic diathesis and keratosis pilaris on the extensor extremities. KPA is comprised of three distinct clinical subtypes: keratosis pilaris atrophicans faciei, atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans. Affected individuals may present with features overlapping the 3 subtypes.
A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance.
An autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis neural hearing loss and midfacial hypoplasia.
An autosomal recessive neurodevelopmental disorder characterized by multiple congenital anomalies affecting the ocular, renal, skeletal, and sometimes cardiac systems, defects in urogenital and limb morphogenesis, poor overall growth, microcephaly, and global developmental delay.
An autosomal recessive, multisystem disorder characterized by severe global developmental delay, sensorineural hearing loss, poor overall growth, mild facial dysmorphism, gastrointestinal anomalies such as gastroesophageal reflux or midgut malrotation, and a striking lack of tear fluid, saliva, and sweat.
Bullous acrokeratotic poikiloderma of Kindler and Weary
Poikiloderma congenital with bullae Weary type
An autosomal recessive skin disorder characterized by skin blistering, photosensitivity, progressive poikiloderma, and extensive skin atrophy. Additional clinical features include gingival erosions, ocular, esophageal, gastrointestinal and urogenital involvement, and an increased risk of mucocutaneous malignancy.
An autosomal dominant disorder characterized by the triad of dysmorphic features, congenital myopathy, and susceptibility to malignant hyperthermia. Variable expressivity has been reported in several cases.
Mesomelic dysplasia, Steichen-Gersdorf type
An autosomal dominant disease characterized by developmental delay, impaired intellectual development, seizures, short stature, mesomelic dysplasia, dysmorphic facial features, horseshoe or hypoplastic kidney, and failure to thrive.
Chromosome 9q subtelomeric deletion syndrome
A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable intellectual disability, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms. KLEFS1 patients additionally manifest brachy(micro)cephaly, congenital heart defects, and urogenital defects.
A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable intellectual disability, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms.
Klippel-Feil syndrome 1, autosomal dominant
Cervical vertebral fusion autosomal dominant
A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. Deafness is a feature in some cases and may be of sensorineural, conductive, or mixed type.
Klippel-Feil syndrome 2, autosomal recessive
Cervical vertebral fusion autosomal recessive
A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement.
Klippel-Feil syndrome 3, autosomal dominant
Klippel-Feil syndrome 4, autosomal recessive, with nemaline myopathy and facial dysmorphism
A form of Klippel-Feil syndrome, a skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. KFS4 features additionally include myopathy, mild short stature, microcephaly, and distinctive facies.
Congenital disease characterized by malformations of capillary (98% of KTS patients), venous (72%) and lymphatic (11%) vessels, and bony and soft tissue hypertrophy that leads to large cutaneous hemangiomata with hypertrophy of the related bones and soft tissues.
Moderately severe chondrodysplasia phenotype that results from mutations in the COL2A1 gene. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss.
Retinal detachment and occipital encephalocele
A developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia.
An autosomal dominant form of Knobloch syndrome characterized by high myopia, vitreoretinal degeneration, retinal detachment, occipital encephalocele or scalp lesions, and mild to severe psychomotor delay.
An autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discoloration of the teeth. Although the phenotype is consistent, there is variability. Intellectual disability is related to the severity of seizures, and the disorder can thus be considered an epileptic encephalopathy. Some infants show normal development until seizure onset, whereas others are delayed from birth. The most severely affected individuals have profound intellectual disability, never acquire speech, and become bedridden early in life.
A disorder characterized by global developmental delay, moderately to severely impaired intellectual development, poor or absent speech, delayed motor skills, and early-onset epilepsy in many patients. Most affected individuals have feeding difficulties, poor overall growth, dysmorphic facial features, and significant dental anomalies resembling amelogenesis imperfecta. More variable features include visual defects, behavioral abnormalities, and non-specific involvement of other organ systems. KTZSL transmission pattern is consistent with autosomal dominant inheritance with incomplete penetrance and variable expressivity.
An autosomal dominant, multisystem disorder characterized by hypotonia, developmental delay, moderate to severe intellectual disability, and distinctive dysmorphic features including tall, broad forehead, long face, upslanting palpebral fissures, epicanthal folds, tubular nose with bulbous nasal tip, and large ears. Expressive language development is particularly impaired compared with receptive language or motor skills. Additional features include social and friendly behavior, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies.
Skeletal overgrowth with facial dysmorphism, hyperelastic skin, white matter lesions, and neurologic deterioration
A syndrome characterized by somatic overgrowth, distinctive facial features, hyperelastic and fragile skin, and progressive neurologic deterioration with white matter lesions on brain imaging.
Pituitary dwarfism with normal immunoreactive growth hormone and low somatomedin
A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy.
Galactosylceramide beta-galactosidase deficiency
An autosomal recessive disorder characterized by insufficient catabolism of several galactolipids that are important for normal myelin production. Four clinical forms are recognized. The infantile form accounts for 90% of cases. It manifests before six months of age with irritability, spasticity, arrest of motor and mental development, and bouts of temperature elevation without infection. This is followed by myoclonic jerks of arms and legs, oposthotonus, hypertonic fits, and mental regression, which progresses to a severe decerebrate condition with no voluntary movements and death from respiratory infections or cerebral hyperpyrexia before 2 years of age. Cases with later onset present with unexplained blindness, weakness and sensorimotor peripheral neuropathy, mental deterioration and death.
Krabbe disease, atypical, due to saposin A deficiency
An autosomal recessive disorder of galactosylceramide metabolism. Clinical features include neurologic regression around age 3 months, loss of spontaneous movements, hyporeflexia, generalized brain atrophy, and diffuse white matter dysmyelination.
Pallidopyramidal degeneration with supranuclear upgaze paresis and dementia
A rare form of autosomal recessive juvenile or early-onset, levodopa-responsive parkinsonism. In addition to typical parkinsonian signs, clinical manifestations of Kufor-Rakeb syndrome include behavioral problems, facial tremor, pyramidal tract dysfunction, supranuclear gaze palsy, and dementia.
Kuru is transmitted during ritualistic cannibalism, among natives of the New Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from 3 to 12 month after onset.
An autosomal dominant neurodevelopmental disorder characterized mainly by mild global developmental delay apparent from infancy or early childhood, and behavioral problems, including autism in most patients. Intellectual development may be mildly delayed, borderline, or even normal. Additional variable systemic features may include poor overall growth, hypotonia, distal skeletal anomalies, seizures, and non-specific dysmorphic facial features.
A rare autosomal recessive disorder clinically characterized by mild psychomotor delay in the first years of life, followed by progressive cerebellar ataxia, dysarthria and moderate to severe intellectual disability. Diagnosis is based on the presence of an excess of L-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid.
L-ferritin deficiency dominant and recessive
A condition characterized by low levels of ferritin in serum and tissues in the absence of other hematological symptoms. Seizures and mild neuropsychologic impairment may manifest in individuals with complete ferritin deficiency.
A condition resulting in the imbalance between tear production and tear drainage. Infants typically manifest persistent epiphora and/or recurrent infections of the lacrimal pathway, such as conjunctivitis. LCDD is caused by failure of the nasolacrimal duct to open into the inferior meatus.
Lacrimo-auriculo-dento-digital syndrome 1
A form of lacrimo-auriculo-dento-digital syndrome, an autosomal dominant disease characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.
Lacrimo-auriculo-dento-digital syndrome 2
Lacrimo-auriculo-dento-digital syndrome 3
A condition with no deleterious effects on health. LDHBD is of interest to laboratory medicine mainly because it can cause misdiagnosis in those disorders in which elevation of serum LDH is expected.
An autosomal dominant, neurodevelopmental disorder characterized by global developmental delay, intellectual disability, language and motor impairment, and distinct facial features. Additional variable skeletal abnormalities may also be present.
Autosomal recessive rare skeletal dysplasia characterized by severe short stature owing to shortening and maldevelopment of the mesomelic and rhizomelic segments of the limbs. Associated malformations are rarely reported and intellect is normal in all affected subjects reported to date.
Language delay and attention deficit-hyperactivity disorder/cognitive impairment with or without cardiac arrhythmia
Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia
An autosomal recessive neurodevelopmental disorder characterized by speech impairment and variable expressivity of attention deficit hyperactivity disorder. Some patients manifest developmental and motor delay, hypotonia, and sinus-node dysfunction.
A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.
An osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication.
Autosomal dominant disorder characterized by onset in the fifth to sixth decade with night blindness and punctate yellow-white deposits in the retinal fundus, progressing to severe central and peripheral degeneration, with choroidal neovascularization and chorioretinal atrophy.
A very rare skeletal disorder with facial anomalies, hypotonia and neurologic dysfunction due to meningocele, a protrusion of the meninges, unaccompanied by neural tissue, through a bony defect in the skull or vertebral column. LMNS facial features include hypertelorism and telecanthus, high arched eyebrows, ptosis, mid-facial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Additional variable features are connective tissue abnormalities, aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis.
An autosomal recessive disorder characterized by multiple congenital anomalies affecting axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage.
An autosomal recessive syndrome characterized by progressive spinocerebellar degeneration, spastic paraplegia, intellectual disability, hypogonadism, dwarfism, and chorioretinopathy. Trichomegaly is absent.
Duplication of fibula and ulna with absence of tibia and radius
Mirror hands and feet with nasal defects
A rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. Some patients do not have nasal abnormalities (segmental Laurin-Sandrow syndrome).
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Retinitis pigmentosa juvenile LRAT-related
Severe early-onset retinal dystrophy LRAT-related
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or almost absent pupillary responses, photophobia, high hyperopia and keratoconus.
A form of Leber congenital amaurosis, a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. LCA19 is an autosomal recessive form characterized by reduced vision in early childhood and severely reduced responses of both rods and cones.
Leber congenital amaurosis with early-onset deafness
An autosomal dominant disease characterized by severe retinal degeneration and sensorineural hearing loss. Symptoms occur within the first decade of life. Onset at birth is observed in some patients.
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Leber hereditary optic neuropathy with dystonia
Familial dystonia with visual failure and striatal lucencies
A form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. LDYT is characterized by the association of optic atrophy and central vision loss with dystonia.
Leber hereditary optic neuropathy, autosomal recessive
Mitochondrial complex I deficiency, nuclear type 38
An autosomal recessive form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance.
Leber hereditary optic neuropathy, modifier
Leber hereditary optic neuropathy, modifier of
Leber hereditary optic neuropathy susceptibility
Modifier of Leber hereditary optic neuropathy
A form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Leber hereditary optic neuropathy is maternally inherited in most case and results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. Mutations in modifier genes can influence disease expression. LOAM exhibits increased penetrance and earlier age of onset compared to Leber optic atrophy caused by MTND4 primary mutations, due to the action of mutations in PRICKLE3 as a modifier gene.
Lecithin-cholesterol acyltransferase deficiency
Lecithin:cholesterol acyltransferase deficiency
A disorder of lipoprotein metabolism characterized by inadequate esterification of plasmatic cholesterol. Two clinical forms are recognized: complete LCAT deficiency and fish-eye disease. LCATD is generally referred to the complete form which is associated with absence of both alpha and beta LCAT activities resulting in esterification anomalies involving both HDL (alpha-LCAT activity) and LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure.
Left ventricular non-compaction with or without congenital heart defects
Non-compaction of left ventricular myocardium isolated autosomal dominant type 1
Non-compaction of left ventricular myocardium with congenital heart defects
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC1 is an autosomal dominant condition.
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC10 is an autosomal dominant condition.
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC3 is an autosomal dominant condition.
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC5 is an autosomal dominant condition.
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC7 is an autosomal dominant condition.
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC8 is an autosomal dominant condition.
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC9 is an autosomal dominant condition.
The defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava.
Characterized by loss of circulation to the femoral head, resulting in avascular necrosis in a growing child. Clinical pictures of the disease vary, depending on the phase of disease progression through ischemia, revascularization, fracture and collapse, and repair and remodeling of the bone.
An autosomal dominant syndrome characterized mainly by cafe-au-lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities, and features of attention-deficit hyperactivity disorder.
Leigh syndrome due to mitochondrial complex I deficiency
Leigh syndrome due to mitochondrial complex II deficiency
Leigh syndrome due to mitochondrial complex III deficiency
Leigh syndrome due to mitochondrial complex IV deficiency
Leigh syndrome due to mitochondrial complex V deficiency
Necrotizing encephalopathy infantile subacute of Leigh
An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.
A syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. LMHD is characterized by the combination of sclerosing bone dysplasia, intellectual disability and distinct craniofacial, dental, cutaneous and distal limb anomalies. The progressive generalized hyperostosis associated with this syndrome affects the cranium, the vertebrae and the diaphyses of tubular bones, leading to severe growth restriction.
A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive.
Obesity due to congenital leptin deficiency
A rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.
Morbid obesity due to leptin receptor deficiency
A rare disease characterized by normal levels of serum leptin, hyperphagia and severe obesity from an early age. Additional features include alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism.
Dominantly inherited skeletal dysplasia characterized by moderate short stature predominantly because of short mesomelic limb segments. It is often associated with the Madelung deformity of the wrist, comprising bowing of the radius and dorsal dislocation of the distal ulna.
Characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, intellectual disability, and compulsive self-mutilation.
An autosomal dominant disorder characterized by global developmental delay, intellectual disability of variable degree, and speech and language delay apparent from infancy or early childhood. Behavioral disorders are observed in most patients. Additional variable features include seizures, hypotonia, gait abnormalities, visual and cardiac defects, and non-specific facial dysmorphism.
An autosomal recessive progeroid syndrome characterized by short stature, pinched facial features, prematurely gray hair, scleroderma-like skin changes, small kidneys and consecutive kidney failure, followed by severe arterial hypertension.
Lethal congenital contracture syndrome 1
Multiple contracture syndrome Finnish type
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS1 patients manifest early fetal hydrops and akinesia, micrognathia, pulmonary hypoplasia, pterygia, and multiple joint contractures. It leads to prenatal death.
Lethal congenital contracture syndrome 10
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth.
Lethal congenital contracture syndrome 11
Lethal congenital contracture syndrome 2
Israeli Bedouin multiple contracture syndrome type A
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS2 patients manifest craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy and a unique feature of a markedly distended urinary bladder (neurogenic bladder defect). The phenotype suggests a spinal cord neuropathic etiology.
Lethal congenital contracture syndrome 3
Multiple contractural syndrome Israeli Bedouin type B
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS3 patients present at birth with severe multiple joint contractures and severe muscle wasting and atrophy, mainly in the legs. Death occurs minutes to hours after birth due to respiratory insufficiency. The phenotype can be distinguished from that of LCCS1 by the absence of hydrops, fractures and multiple pterygia, and from LCCS2 by the absence of neurogenic bladder defect.
Lethal congenital contracture syndrome 4
Lethal congenital contracture syndrome 5
Autosomal recessive lethal centronuclear myopathy
Lethal congenital contracture syndrome 6
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS6 features include severe polyhydramnios and absent stomach, in addition to multiple contracture deformities.
Lethal congenital contracture syndrome 7
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS7 is a severe axoglial disease characterized by congenital distal joint contractures, polyhydramnios, reduced fetal movements, and motor paralysis leading to death early in the neonatal period.
Lethal congenital contracture syndrome 8
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS8 is an axoglial form of arthrogryposis multiplex congenita, characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period.
Lethal congenital contracture syndrome 9
Leucine-sensitive hypoglycemia of infancy
Rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine.
Leukemia acute lymphoblastic B-hyperdiploid
A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes.
A subtype of acute leukemia, a cancer of the white blood cells. Acute lymphoblastic anemia is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes.
A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
A chronic leukemia in which functionally incompetent B-lymphocytes progressively accumulate in the bone marrow, blood, and lymphoid tissues. The clinical evolution of the disorder is heterogeneous, with some patients having indolent disease and others having aggressive disease and short survival.
A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts.
Atypical chronic myeloid leukemia BCR-ABL1 negative
A myeloproliferative disorder that shares clinical and laboratory features with chronic myeloid leukemia but lacks the pathognomonic Philadelphia chromosome and the corresponding BCR/ABL1 fusion transcript. Features include myeloid predominance in the bone marrow, myeloid proliferation and low leukocyte alkaline phosphatase value, splenomegaly, hepatomegaly, elevated white blood cell count. Enlarged spleen may also be associated with a hypermetabolic state, fever, weight loss, and chronic fatigue. The enlarged liver may contribute to the patient's weight loss.
An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions.
A disorder characterized by recurrent bacterial infections without pus formation, leukocytosis and major bleeding disorders.
Leukodystrophy and acquired microcephaly with or without dystonia
An autosomal recessive neurologic disorder characterized by profound intellectual disability, dystonia, postnatal microcephaly, and white matter abnormalities consistent with leukodystrophy.
Leukodystrophy with vanishing white matter
Childhood ataxia with central nervous system hypomyelinization
Leukoencephalopathy with vanishing white matter
A leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
Leukodystrophy, childhood-onset, remitting
An autosomal dominant disorder characterized by loss of developmental abilities, demyelination and leukodystrophy on brain imaging, triggered by fever or infection in the first year of life. Abnormalities almost completely resolve over a period of 1 to 2 years, and affected children regain normal development accompanied by remyelination.
Leukodystrophy, demyelinating, autosomal dominant, adult-onset
Pelizaeus-Merzbacher disease autosomal dominant
Pelizaeus-Merzbacher disease late-onset type
A slowly progressive and fatal demyelinating leukodystrophy, presenting in the fourth or fifth decade of life. Clinically characterized by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. It differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis.
Sudanophilic leukodystrophy Paelizeus-Merzbacher type
An X-linked recessive disorder of the central nervous system in which myelin is not formed properly. Clinically characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay.
An autosomal recessive neurologic disorder characterized by postnatal microcephaly, severely delayed psychomotor development, hypomyelination, and reduced cerebral white-matter volume.
An autosomal recessive neurologic disorder characterized by brain hypomyelination, delayed psychomotor development, intellectual disability, tremor and other neurologic symptoms. Some patients may additionally manifest non-neurologic features, particularly dental abnormalities and hypogonadotropic hypogonadism.
An autosomal recessive neurologic disorder characterized by developmental delay, spasticity, truncal hypotonia, acquired microcephaly, intellectual disability with variable seizure disorder, accompanied by thin corpus callosum, paucity of white matter and delayed myelination.
An autosomal recessive neurodegenerative disorder with infantile onset, affecting mainly the central white matter. Clinical features include early feeding difficulties, global developmental delay, postnatal progressive microcephaly, truncal hypotonia, spasticity, and variable neurologic deficits, such as visual impairment.
An autosomal recessive, severe disorder characterized by atrophy of the basal ganglia and cerebellum, hypomyelination, severe developmental delay, typically without intentional movements and language development, and microcephaly. Almost all patients exhibit spasticity, extrapyramidal movement abnormalities, and severe drug-resistant epilepsy. Disease onset is early in infancy, and most patients die in the first years of life.
An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with thinning of the corpus callosum. Clinical features include motor and cognitive impairment appearing in the first or second decade of life, dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss.
An autosomal dominant disorder characterized by hypomyelination, leukodystrophy, and thin corpus callosum observed on brain imaging. Clinical features include hypotonia, nystagmus, and mildly delayed motor development with onset in infancy, ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties.
An autosomal recessive neurodevelopmental disorder characterized by atrophy of cerebral cortex, spinal cord and cerebellum, thin corpus callosum, abnormal signals in the basal ganglia, and features suggesting hypo- or demyelination observed on brain imaging. Clinical manifestations include lack of development, absent speech, microcephaly, spasticity, seizures, and contractures.
An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with progressive atrophy of the corpus callosum, thalami and cerebellum, and peripheral neuropathy. Clinical features include very poor psychomotor development, dystonia, severe spasticity, seizures, and failure to thrive.
Leukodystrophy, hypomyelinating, 19, transient infantile
An autosomal dominant disorder characterized by marked hypomyelination on brain imaging, congenital nystagmus, and motor delay manifesting in early infancy. Both neurologic impairment and abnormal brain imaging spontaneously resolve during childhood.
Pelizaeus-Merzbacher-like disease autosomal recessive type 1
Pelizaeus-Merzbacher-like disease type 1
An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.
An autosomal recessive disorder characterized by neuroregression and loss of motor, language and cognitive skills, after a normal early development. Disease onset is between 12 and 18 month of age. Patients show poor overall growth, microcephaly, feeding difficulties and spastic quadriplegia. Some patients may have seizures. Death in childhood may occur. Hypomyelinating leukodystrophy with subcortical and periventricular white matter abnormalities is seen on brain imaging.
An autosomal recessive neurodegenerative disorder characterized by global developmental delay, loss of motor, speech and cognitive milestones in the first decades of life, and diffuse hypomyelination of the white matter and atrophy of the cerebellum and corpus callosum observed on brain imaging. Clinical features include nystagmus, ataxia, dystonia, and spasticity. Other more variable features are feeding difficulties, poor overall growth with microcephaly, optic atrophy, and seizures.The disorder is progressive and may lead to premature death.
An autosomal dominant disorder characterized by global developmental delay, mildly impaired intellectual development, motor impairment, limb spasticity, dysarthria, and eye abnormalities including hypermetropia. Brain imaging shows hypomyelinating leukodystrophy.
Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy
An autosomal recessive neurodegenerative disorder with systemic manifestations. Affected individuals show delayed motor development and ataxic gait in early childhood that progresses to spastic paraplegia with loss of ambulation in the first decades of life. Additional features include progressive sensorineural hearing loss, hepatic dysfunction, and dilated cardiomyopathy. Death occurs in the first or second decades. Brain imaging shows hypomyelination, diffuse white matter abnormalities, and thin corpus callosum.
An autosomal dominant disorder characterized by global developmental delay apparent in infancy, impaired intellectual development, and loss of developmental milestones and ambulation. Brain imaging shows non-progressive severe cerebral atrophy, ventriculomegaly, hypomyelinating leukodystrophy, and thinning of the corpus callosum.
A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system.
A severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound intellectual disability. Death usually occurs within the first two decades of life.
Hypomyelination with congenital cataract
A hypomyelinating leukodystrophy associated with congenital cataract. It is clinically characterized by congenital cataract, progressive neurologic impairment, and diffuse myelin deficiency. Affected individuals experience progressive pyramidal and cerebellar dysfunction, muscle weakness and wasting prevailingly in the lower limbs. Mental deficiency ranges from mild to moderate. HLD5 shows clinical variability, but features of hypomyelination combined with increased periventricular white matter water content are consistently observed.
Hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum
A neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen.
Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism
Ataxia delayed dentition and hypomyelination
Leukodystrophy hypomyelinating with hypodontia and hypogonadotropic hypogonadism 4H syndrome
Leukoencephalopathy hypomyelinating with ataxia and delayed dentition
Tremor-ataxia with central hypomyelination
An autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability.
Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism
Cerebellar hypoplasia with endosteal sclerosis
An autosomal recessive neurodegenerative disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism.
An autosomal recessive neurodegenerative disorder characterized by delayed psychomotor development, severe spasticity, nystagmus, and ataxia associated with diffuse hypomyelination apparent on brain MRI.
Leukodystrophy, progressive, early childhood-onset
A form of leukodystrophy, a disorder of myelin production or maintenance affecting the central nervous system. PELCO features include neurological regression between 6 and 13 months of age, truncal hypotonia, appendicular spasticity, dystonia, optic disk pallor, peripheral neuropathy and neurogenic bladder. Brain imaging shows progressive diffuse abnormal white matter signals, cerebral atrophy, and thin corpus callosum. Sural nerve biopsy shows decreased myelination. PLDECO inheritance is autosomal recessive.
An autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities.
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation
Autosomal recessive disease and is defined on the basis of a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. Affected individuals develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline.
Leukoencephalopathy with dystonia and motor neuropathy
A syndrome characterized by leukoencephalopathy, dystonic head tremor, spasmodic torticollis and reduced tendon reflexes in lower extremities. Additional features include hyposmia, pathologic saccadic eye movements, a slight hypoacusis, accumulation of branched-chain pristanic acid in plasma, and the presence of abnormal bile alcohol glucuronides in urine.
Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate
An autosomal recessive disorder characterized by acute, reversible neurological deterioration during febrile illness. Patients exhibit reversible leukoencephalopathy and increased urinary excretion of alpha-ketoglutarate.
Leukoencephalopathy, cystic, without megalencephaly
An infantile-onset syndrome of cerebral leukoencephalopathy. Affected newborns develop microcephaly and neurologic abnormalities including psychomotor impairment, seizures and sensorineural hearing impairment. The brain shows multifocal white matter lesions, anterior temporal lobe subcortical cysts, pericystic abnormal myelination, ventriculomegaly and intracranial calcifications.
Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome
An autosomal dominant disorder characterized by global developmental delay apparent in early childhood, cognitive impairment, ataxia, poor or absent speech with dysarthria, hypotonia, hypertonia, extrapyramidal signs, tremor, and abnormal involuntary movements. Affected individuals also exhibit neurological regression in the setting of febrile illness or infection. Many patients have seizures. Brain imaging shows diffuse white matter abnormalities with poor myelination.
Leukoencephalopathy, hereditary diffuse, with spheroids 1
Autosomal dominant leukoencephalopathy with neuroaxonal spheroids
Familial progressive subcortical gliosis
Leukoencephalopathy, adult-onset, with axonal spheroids and pigmented glia
Leukoencephalopathy, diffuse hereditary, with spheroids
An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.
Leukoencephalopathy, hereditary diffuse, with spheroids 2
Leukoencephalopathy, hereditary diffuse, with spheroids, Swedish type
Swedish type hereditary diffuse leukoencephalopathy with spheroids
An autosomal dominant neurodegenerative disorder characterized by progressive cognitive and executive dysfunction, psychiatric disturbances, and neurologic symptoms, such as gait abnormalities, paresis, seizures, and rigidity. Symptom onset is usually in adulthood, although earlier onset has been reported. Some patients have an acute encephalopathic course with severe neurologic decline resulting in early death, whereas other patients have a more protracted and chronic disease course. Neuropathologic examination shows a leukoencephalopathy with axonal spheroids and myelination defects.
Leukoencephalopathy, megalencephalic, with subcortical cysts, 1
Leukoencephalopathy with swelling and cysts
Vacuolating megalencephalic leukoencephalopathy with subcortical cysts
A syndrome of cerebral leukoencephalopathy and megalencephaly characterized by ataxia, spasticity, seizures, delay in motor development and mild intellectual disability. The brain appears swollen on magnetic resonance imaging, with diffuse white-matter abnormalities and the invariable presence of subcortical cysts in frontal and temporal lobes.
Leukoencephalopathy, megalencephalic, with subcortical cysts, 2A
A neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. The brain appears swollen on magnetic resonance imaging with white-matter abnormalities and subcortical cysts, in all stages of the disease.
Leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome
A disorder characterized by delayed motor development, speech delay with dysarthria, hypertonia, progressive spasticity, hyperreflexia, and bradykinesia. Cognition is normal. Patients manifest anxiety and attention deficit-hyperactivity disorder.
Leukoencephalopathy, progressive, infantile-onset, with or without deafness
An autosomal recessive, complex neurodegenerative disorder apparent from infancy. LEPID is characterized by early-onset progressive leukoencephalopathy with brainstem and spinal cord calcifications, sensorineural deafness in most patients, global developmental delay with cognitive impairment and poor or absent speech, developmental regression, and neurologic deterioration. Additional more variable features may include poor overall growth with microcephaly, seizures, visual loss, microcytic anemia, and hepatic enlargement or abnormal liver enzymes. Premature death is common.
Leukoencephalopathy, progressive, with ovarian failure
An autosomal recessive neurodegenerative disorder characterized by childhood- to adulthood-onset of signs of neurologic deterioration consisting of ataxia, spasticity, and cognitive decline with features of frontal lobe dysfunction. Brain MRI shows leukoencephalopathy with striking involvement of deep white matter, and cerebellar atrophy. All female patients develop premature ovarian failure.
Cerebellar granule cell hypertrophy and megalencephaly
Dysplastic gangliocytoma of the cerebellum
A rare disease characterized by the occurrence of a slowly enlarging mass within the cerebellar cortex corresponding histologically to a cerebellar hamartoma. It manifests, most commonly in the third and fourth decades of life, with increased intracranial pressure, headache, nausea, cerebellar dysfunction, occlusive hydrocephalus, ataxia, visual disturbances and other cranial nerve palsies. Various associated abnormalities may be present such as megalencephaly, microgyria, hydromyelia, polydactyly, partial gigantism, macroglossia. LDD is part of the PTEN hamartoma tumor syndromes spectrum that also includes Cowden syndrome.
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, epilepsy, ptosis, hypothyroidism, and variable cardiac and genital anomalies. Additional features may include seizures, short stature, hypotonia, and brain imaging anomalies, such as cortical atrophy.
Sarcoma family syndrome of Li and Fraumeni
An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.
A form of Li-Fraumeni syndrome, a familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.
An autosomal dominant disorder characterized by global developmental delay, mild to moderate intellectual disability, speech and language impairment, and variable facial dysmorphism. Some patients have seizures and autistic features. Brain imaging abnormalities are observed in some patients and include decreased white matter volume, enlarged ventricles, thin corpus callosum, and gray matter nodular heterotopia.
An autosomal dominant syndrome characterized by a highly variable phenotype and severity. The broad spectrum of clinical features includes developmental delay, intellectual disability, ataxia, axial hypotonia, and poor or absent speech, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic craniofacial dysmorphism. About half of patients have cerebral and cerebellar atrophy, and thin corpus callosum.
Spondyloepimetaphyseal dysplasia, Liberfarb type
An autosomal recessive multisystem disorder affecting the eye, ear, bone, and brain development. Clinical features include early-onset retinal degeneration, congenital cataracts, sensorineural hearing loss, microcephaly, intellectual disability, white matter changes, mild facial dysmorphism, and skeletal dysplasia with platyspondyly, scoliosis and short stature.
Spinocerebellar ataxia, autosomal recessive, 19
An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss.
A form of Liddle syndrome, an autosomal dominant disorder characterized by early onset of hypertension, hypokalemic alkalosis, and suppression of plasma renin activity and aldosterone secretion.
Carpal synostosis with dysplastic elbow joints and brachydactyly
An upper limb-malformation syndrome characterized by the combination of dysplastic elbow joints and the fusion of wrist bones with consequent radial deviation.
Characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.
Absence of ulna and fibula with severe limb deficiency
Limb/pelvis/uterus-hypoplasia/aplasia syndrome
A syndrome of severe deficiency of the extremities due to hypo- or aplasia of one or more long bones of one or more limbs. Pelvic manifestations include hip dislocation, hypoplastic iliac bone and aplastic pubic bones. Thoracic deformity, unusual facies and genitourinary anomalies can be present.
Characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.
Linear skin defects with multiple congenital anomalies 1
Microphthalmia, dermal aplasia and sclerocornea
A disorder characterized by dermal, ocular, neurological and cardiac abnormalities. LSDMCA1 main features are unilateral or bilateral microphthalmia, linear skin defects in affected females, and in utero lethality for males. Skin defects are limited to the face and neck, consisting of areas of aplastic skin that heal with age to form hyperpigmented areas. Additional features in female patients include agenesis of the corpus callosum, sclerocornea, chorioretinal abnormalities, infantile seizures, congenital heart defect, intellectual disability, and diaphragmatic hernia. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Linear skin defects with multiple congenital anomalies 2
Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies
A distinct form of aplasia cutis congenita presenting as multiple linear skin defects on the face and neck associated with poor growth, microcephaly, and facial dysmorphism. Additional features include intellectual disability, nail dystrophy, short stature and cardiac abnormalities.
Linear skin defects with multiple congenital anomalies 3
Linear skin defects with cardiomyopathy and other congenital anomalies
A disorder characterized by dermal, ocular, neurological and cardiac abnormalities. LSDMCA3 clinical features include linear skin defects on face and neck at birth, lacrimal duct atresia, myopia, nystagmus, strabismus, cardiomyopathy, axial hypotonia, seizures, corpus callosum agenesis, and dilation of lateral ventricles.
Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency
Lipid storage myopathy due to FLAD1 deficiency
An autosomal recessive, inborn error of metabolism characterized by variable mitochondrial dysfunction. Clinical features range from severe cardiac and respiratory insufficiency with onset in infancy and resulting in early death, to mild muscle weakness with onset in adulthood. Some patients show significant improvement with riboflavin treatment. Analysis of skeletal muscle show multiple mitochondrial respiratory chain deficiency and a lipid storage myopathy in most patients.
Familial partial lipodystrophy Dunnigan type
Generalized lipoatrophy associated with diabetes, hepatic steatosis, hypertrophic cardiomyopathy and leukomelanodermic papules
Lipodystrophy familial of limbs and lower trunk
A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.
Familial partial lipodystrophy associated with PPARG mutations
A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.
Familial partial lipodystrophy associated with PLIN1 mutations
A form of lipodystrophy characterized by loss of subcutaneous adipose tissue primarily affecting the lower limbs, insulin-resistant diabetes mellitus, hypertriglyceridemia, and hypertension.
Familial partial lipodystrophy associated with CIDEC mutations
A form of lipodystrophy characterized by loss of subcutaneous adipose tissue affecting limb, femorogluteal and subcutaneous abdominal fat, preservation of visceral, neck and axilliary fat, hepatomegaly, hepatic steatosis and insulin-resistant diabetes.
A form of lipodystrophy characterized by abnormal subcutaneous fat distribution. Affected individuals have increased visceral fat, impaired lipolysis, dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. Some patients manifest muscular dystrophy.
Lipodystrophy, partial, with congenital cataracts and neurodegeneration
Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome
A form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. Affected individuals manifest a gradual loss of subcutaneous adipose tissue in various parts of the body, accompanied by an accumulation of adipose tissue in the face and neck in some cases causing a double chin, fat neck, or cushingoid appearance. FPLD7 is an autosomal dominant form with a variable phenotype. Some patients manifest congenital cataracts and neurodegeneration leading to cerebellar and spinal cord dysfunction.
Rare autosomal recessive disorder characterized by generalized thickening of skin, mucosae and certain viscera. Classical features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. Histologically, there is widespread deposition of hyaline material and disruption/reduplication of basement membrane.
Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries.
A disorder due to a defect in lipoic acid metabolism, resulting in severe lactic acidosis and metabolic decompensation. Variable clinical manifestations include delayed psychomotor development, severe hypotonia, dystonia, loss of head control, coma, bradycardia, and pulmonary hypertension.
A classical lissencephaly. It is characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. The cortex is abnormally thick and poorly organized with 4 primitive layers. Associated with enlarged and dysmorphic ventricles and often hypoplasia of the corpus callosum.
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS10 is an autosomal dominant form clinically characterized by variably delayed development, mildly to moderately impaired intellectual development, language delay, and seizures. Some patients have normal early development and borderline to mild cognitive impairment.
Lissencephaly syndrome Norman-Roberts type
Lissencephaly with cerebellar hypoplasia
A classic type lissencephaly associated with ataxia, intellectual disability, seizures and abnormalities of the cerebellum, hippocampus and brainstem.
A classic type lissencephaly associated with psychomotor retardation and seizures. Features include agyria or pachygyria or laminar heterotopia, severe intellectual disability, motor delay, variable presence of seizures, and abnormalities of corpus callosum, hippocampus, cerebellar vermis and brainstem.
A neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly, and profound intellectual disability.
An autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development.
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS6 features include hypoplasia of the corpus callosum, severe microcephaly and developmental delay.
Lissencephaly 7, with cerebellar hypoplasia
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS7 patients manifest lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy.
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS8 patients manifest delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, hypotonia, cortical gyral abnormalities, and hypoplasia of the corpus callosum, brainstem and cerebellum. LIS8 inheritance is autosomal recessive.
Lissencephaly 9 with complex brainstem malformation
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS9 is an autosomal dominant form clinically characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements. Brain imaging shows malformation of the brainstem, in addition to pachygyria and lissencephaly.
A classic lissencephaly characterized by intellectual disability and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.
Lissencephaly X-linked with ambiguous genitalia
A classic type lissencephaly associated with abnormal genitalia. Patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.
An autosomal recessive disease characterized by severe neonatal liver cirrhosis and progressive hepatic dysfunction. Affected individuals have feeding difficulties, poor overall growth, and failure to thrive with signs of malnutrition. Additional features include jaundice, abdominal distension, hepatomegaly or hepatosplenomegaly, and ascites in most patients.
Acute infantile liver failure due to mtDNA-encoded proteins synthesis defect
A transient disorder of hepatic function characterized by elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, increased serum lactate. Patients who survive the initial acute episode can recover, show normal development and have no recurrence.
Marfanoid disorder-craniosynostosis syndrome
An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit.
Familial aortic aneurysm thoracic type 3
Thoracic aortic aneurysms and dissection 2
Loeys-Dietz syndrome with osteoarthritis
An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and intellectual disability.
Aortic and cerebral aneurysm with arterial tortuosity and skeletal manifestations
An aortic aneurysm syndrome with widespread systemic involvement. LDS4 is characterized by arterial tortuosity, aortic dissection, intracranial aneurysm and subarachnoid hemorrhage, hypertelorism, bifid uvula, pectus deformity, bicuspid aortic valve, arachnodactyly, scoliosis, foot deformities, dural ectasia, joint hyperflexibility, and thin skin with easy bruising and striae.
A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS5 additional variable features include mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity. LDS5 patients do not manifest remarkable aortic or arterial tortuosity, and there is no strong evidence for early aortic dissection.
A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Most LDS6 patients have thoracic aortic aneurysm involving the ascending aorta and/or aortic root, but cerebral and iliac arteries can be affected, and abdominal aortic aneurysm has been observed. Arterial tortuosity involving cerebral vessels, the aorta, and/or iliac arteries has also been reported. LDS6 inheritance is autosomal dominant.
A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
A form of long QT syndrome, a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
An autosomal dominant form of long QT syndrome, a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
Susceptibility to acquired Long QT syndrome 2
A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Deafness is often associated with long QT syndrome type 2.
A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 4 shows many atypical features compared to classical long QT syndromes, including pronounced sinus bradycardia, polyphasic T waves and atrial fibrillation. Cardiac repolarization defects may be not as severe as in classical LQT syndromes and prolonged QT interval on EKG is not a consistent feature.
Susceptibility to acquired Long QT syndrome 5
Susceptibility to acquired Long QT syndrome 6
Andersen cardiodysrhythmic periodic paralysis
Periodic paralysis, potassium-sensitive cardiodysrhythmic type
A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 7 manifests itself as a clinical triad consisting of potassium-sensitive periodic paralysis, ventricular ectopy and dysmorphic features.
A form of long QT syndrome, a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. LQT8 transmission pattern is consistent with autosomal dominant inheritance with incomplete penetrance.
Long-chain 3-hydroxyl-CoA dehydrogenase deficiency
The clinical features are very similar to TFP deficiency. Biochemically, LCHAD deficiency is characterized by reduced long-chain 3-hydroxyl-CoA dehydrogenase activity, while the other enzyme activities of the TFP complex are normal or only slightly reduced.
In LAHS, anagen hairs are easily pulled from the scalp. The hair is relatively sparse and does not grow long. Hair of fair color and hair shafts of reduced caliber, and an early age of onset are features. Usually the hairs are not fragile and there are no areas of breakage.
An autosomal recessive neurodevelopmental disorder characterized by developmental regression in infancy, delayed psychomotor development, severe intellectual disability, and cerebral and cerebellar atrophy. Additional features include swallowing problems, dystonia, bradykinesia, and continuous manual stereotypies without chorea. Some patients manifest seizures.
Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis
An X-linked renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. LMWPHN is a slowly progressive disorder. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure.
X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, intellectual disability, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination.
Lower urinary tract obstruction, congenital
A disorder characterized by urinary bladder outflow obstruction, which can represent an anatomical blockage or a functional obstruction. The most common anatomical causes are posterior urethral valves at the level of the prostatic urethra, a lesion unique to males. Less common are anterior urethral valves, also called urethral atresia, that can occur in either sex. LUTO is an autosomal dominant disease with variable expression.
A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.
Lung disease, immunodeficiency, and chromosome breakage syndrome
An autosomal recessive chromosome breakage syndrome associated with severe, fatal lung disease in early childhood, following viral pneumonia. LICS is characterized by combined T and B-cell immunodeficiency. Some patients may have mild dysmorphic features.
An autosomal dominant disorder characterized by intrauterine growth retardation, severe intellectual disability, behavioral problems, early-onset seizures, feeding difficulties, and dysmorphic features. White matter abnormalities and delayed myelination are observed on brain imaging.
An autosomal dominant syndrome with a variable phenotype. Clinical features include macrocephaly, distinctive facial appearance, postnatal overgrowth, various degrees of learning difficulties, autism spectrum disorder, and intellectual disability.
Hypergonadotropic hypogonadism male due to LHCGR defect
Leydig cell hypoplasia with male pseudohermaphroditism
Testicular luteinizing hormone resistance
An autosomal recessive disorder characterized by unresponsiveness to luteinizing hormone, defective sexual development in males, and defective follicular development and ovulation, amenorrhea and infertility in females. Two forms of the disorder have been defined in males. Type 1 is a severe form characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high luteinizing hormone levels, total lack of responsiveness to luteinizing and chorionic gonadotropin hormones, lack of breast development, and absent development of secondary male sex characteristics. Type 2, a milder form, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias.
Progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM1 is an autosomal dominant form with variable expression and severity. Onset is usually at birth or in early childhood but can occur later. Affected individuals manifest lymphedema, predominantly in the lower limbs, and hypoplasia of lymphatic vessels. Additional features are hemangioma and nail dysplasia or papillomatosis.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM10 is an autosomal dominant form characterized by the onset of swelling in the lower extremities within the first year of life. Lymphedema may also occur in the neck, upper extremities, and scrotum or labia majora. Gradual resorption generally occurs, although some patients may experience progression complicated by cellulitis. Incomplete penetrance has been observed in some families.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM11 is an autosomal dominant form characterized by onset of lower extremity edema in the second or third decade of life. Some affected individuals may have subclinical lymphatic malformations.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM12 is an autosomal recessive, severe form often resulting in fetal or perinatal demise. It is characterized by dysfunction of core collecting lymphatic vessels, including the thoracic duct and cisterna chyli, non-immune hydrops fetalis, chylothorax, pleural effusions, and chylous ascites.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM3 is an autosomal dominant form with variable severity and reduced penetrance. Affected individuals manifest lymphedema of the lower limbs and some patients have lymphedema of the hands.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM4 is an autosomal dominant form with onset at birth or in early childhood. Affected individuals manifest lymphedema of lower limbs with prominent veins, and impaired lymphatic uptake and drainage. Additional features are nail dysplasia, skin hyperkeratosis and papillomatosis.
Generalized lymphatic dysplasia of Fotiou
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM6 is an autosomal recessive, severe form manifesting as generalized lymphatic dysplasia. It is characterized by uniform, widespread swelling of all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions, and with a high incidence of non- immune hydrops fetalis.
Hydrops fetalis, non-immune, and/or atrial septal defect
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM7 is an autosomal dominant form with variable expressivity. Some individuals present with severe non-immune hydrops fetalis, which may cause perinatal demise or fully resolve after the neonatal period. Others present with no edema and have milder clinical features, such as atrial septal defect or varicose veins as adults.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Adult patients with lymphedema may suffer from recurrent local infections. Impaired lymphatic drainage in the fetus can develop into hydrops fetalis, a severe condition characterized by excessive fluid accumulation in more than two fetal extra-vascular compartments and body cavities, placental enlargement and edema, pericardial or pleural effusion, or ascites. LMPHM8 is an autosomal recessive form characterized by onset in utero and fetal death due to non-immune hydrops fetalis.
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. Impaired lymphatic drainage in the fetus can develop into hydrops fetalis, a severe condition characterized by excessive fluid accumulation in more than two fetal extra-vascular compartments and body cavities, placental enlargement and edema, pericardial or pleural effusion, or ascites. LMPHM9 is an autosomal dominant form with variable expressivity and incomplete penetrance, characterized by the onset of lower-extremity lymphedema in the first decades of life.
A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment.
Lymphedema, primary, with myelodysplasia
A chronic disabling condition characterized by swelling of the extremities due to altered lymphatic flow, associated with myelodysplasia. Patients with lymphedema suffer from recurrent local infections, and physical impairment.
An autosomal dominant disorder characterized by primary limb lymphedema associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices). Swelling of the extremities, due to altered lymphatic flow, usually appears in late childhood or puberty. Most affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia. Drooping of the upper eyelid (ptosis) is a variable feature of the lymphedema-distichiasis syndrome, occurring in about 30% of patients.
A disorder characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities.
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen and general lymphoid tissue, and the presence of large, usually multinucleate, cells (Reed-Sternberg cells). Reed-Sternberg cells compose only 1-2% of the total tumor cell mass. The remainder is composed of a variety of reactive, mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils and histiocytes.
Lymphoma, mucosa-associated lymphoid type
A subtype of non-Hodgkin lymphoma, originating in mucosa-associated lymphoid tissue. MALT lymphomas occur most commonly in the gastro-intestinal tract but have been described in a variety of extranodal sites including the ocular adnexa, salivary gland, thyroid, lung, thymus, and breast. Histologically, they are characterized by an infiltrate of small to medium-sized lymphocytes with abundant cytoplasm and irregularly shaped nuclei. Scattered transformed blasts (large cells) also are present. Non-malignant reactive follicles are observed frequently. A pivotal feature is the presence of lymphoepithelial lesions, with invasion and partial destruction of mucosal glands and crypts by aggregates of tumor cells.
Lymphoproliferative syndrome, EBV-associated, autosomal, 1
A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.
An autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impaired T-cell-dependent B-cell responses and T-cell dysfunction. The phenotype is highly variable, ranging from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation.
An autosomal recessive, early-onset immunologic disorder characterized by increased susceptibility to Epstein-Barr virus infection in B cells, abnormal B-cell proliferation and increased susceptibility to B-cell malignancies, including Hodgkin lymphoma. Patients usually have lymphadenopathy and hypogammaglobulinemia, and may suffer from recurrent infections.
Lymphoproliferative syndrome, X-linked, 1
X-linked progressive combined variable immunodeficiency
A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.
Lymphoproliferative syndrome, X-linked, 2
Hereditary non-polyposis colorectal cancer 1
A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.
Hereditary non-polyposis colorectal cancer 2
Hereditary non-polyposis colorectal cancer 4
Hereditary non-polyposis colorectal cancer 5
Hereditary non-polyposis colorectal cancer 8
A metabolic disorder characterized by increased renal excretion of cationic amino acid (CAA), reduced CAA absorption from intestine, and orotic aciduria. On a normal diet, LPI patients present poor feeding, vomiting, diarrhea, episodes of hyperammoniaemic coma and growth retardation. Hepatosplenomegaly, osteoporosis and a life-threatening pulmonary involvement (alveolar proteinosis) are also seen. Biochemically LPI is characterized by defective transport of dibasic amino acids at the basolateral membrane of epithelial cells in kidney and intestine.
Macrocephaly, acquired, with impaired intellectual development
An autosomal dominant disorder characterized by postnatal macrocephaly and borderline to mild intellectual disability. Additional variable neurodevelopmental features include muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. Some patients present corpus callosum dysgenesis.
Macrocephaly, dysmorphic facies, and psychomotor retardation
An autosomal recessive syndrome characterized by large head and somatic overgrowth, intellectual disability, and facial dysmorphism. Seizures, hypotonia and ataxic gait are observed in some patients.
Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin
An autosomal dominant disease characterized by pharyngeal lymphoid hypertrophy, with adenoid overgrowth, sleep apnea, macrocephaly without structural brain abnormalities, and impaired intellectual development. An increased fraction of fetal hemoglobin has been observed in some patients.
Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD).
Macrocephaly/megalencephaly syndrome, autosomal recessive
An autosomal recessive disorder characterized by abnormal enlargement of the cerebral hemispheres, intellectual disability, large head, optic atrophy and underdeveloped skeletal musculature. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Additional clinical features include behavioral abnormalities, psychosis, learning difficulties, prognathism, myopia and astigmatism.
A congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth affecting the digits or the entire hand or foot.
A malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein. Clinical features are variable and include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Many patients have asymptomatic or indolent disease.
Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
Alport syndrome, with macrothrombocytopenia
Dohle leukocyte inclusions with giant platelets
Giant platelet syndrome with thrombocytopenia
Macrothrombocytopathy, nephritis, and deafness
Macrothrombocytopenia and progressive sensorineural deafness
Macrothrombocytopenia with leukocyte inclusions
An autosomal dominant disorder characterized by thrombocytopenia, giant platelets and Dohle body-like inclusions in peripheral blood leukocytes with variable ultrastructural appearance. Some affected individuals lack leukocyte inclusion bodies on classic staining of peripheral blood smears. Alport syndrome-like features of nephritis, hearing loss, and eye abnormalities are present in some patients.
Macrothrombocytopenia, isolated, 1, autosomal dominant
A congenital blood disorder characterized by increased platelet size and decreased number of circulating platelets.
Macrothrombocytopenia, isolated, 2, autosomal dominant
A congenital blood disorder characterized by increased platelet size and decreased number of circulating platelets. Affected individuals usually are asymptomatic and do not have increased bleeding episodes.
Macrocephaly alopecia cutis laxa and scoliosis syndrome
Tall forehead, sparse hair, skin hyperextensibility, and scoliosis
A complex disorder of elastic tissue characterized by sagging skin and occasionally by life-threatening visceral complications.
A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
Macular degeneration, atrophic, X-linked
An ocular disorder characterized by macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. Some patients manifest extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) show normal cone and rod responses in some affected males despite advanced macular degeneration.
An ocular disorder characterized by macular changes resulting in progressive loss of visual acuity.
Macular dystrophy with central cone involvement
An ocular disease characterized by decreased visual acuity, slight pigmentary changes and color vision abnormalities, becoming apparent in the third to sixth decade of life. Fundus anomalies are variable and include bull's eye maculopathy, severe atrophy of central fovea, relatively spared fovea with surrounding atrophic ring, central retinal pigment epithelium and/or choroid changes, pale or atrophic peripapillary area, pale optic disk, relatively spared periphery, and slightly or moderately attenuated vessels.
An ocular disease characterized by bilateral, progressive corneal opacification, and reduced corneal sensitivity. Onset occurs in the first decade, usually between ages 5 and 9. Painful attacks with photophobia, foreign body sensations, and recurrent erosions occur in most patients. The disease is due to deposition of an unsulfated keratan sulfate both within the intracellular space (within the keratocytes and endothelial cells) and in the extracellular corneal stroma. Macular corneal dystrophy is divided into the clinically indistinguishable types I, IA, and II based on analysis of the normally sulfated, or antigenic, keratan sulfate levels in serum and immunohistochemical evaluation of the cornea. Patients with types I and IA macular corneal dystrophy have undetectable serum levels of antigenic keratan sulfate, whereas those with type II macular corneal dystrophy have normal or low levels, depending on the population examined.
Butterfly dystrophy of retinal pigment epithelium
Macular dystrophy, butterfly-shaped pigmentary
Patterned dystrophy of retinal pigment epithelium
A form of retinal patterned dystrophy, a heterogeneous group of macular disorders that includes reticular (fishnet-like) dystrophy, macroreticular (spider-shaped) dystrophy and butterfly-shaped pigment dystrophy.
Macular dystrophy, butterfly-shaped pigmentary, 2
A form of retinal patterned dystrophy, a heterogeneous group of macular disorders caused by abnormal accumulation of lipofuscin in the retinal pigment epithelium. Lipofuscin distribution can show various shapes that define different types of macular dystrophy, including reticular (fishnet-like) dystrophy, macroreticular (spider-shaped) dystrophy and butterfly-shaped pigment dystrophy. MDPT2 is an autosomal dominant form characterized by bilateral accumulation of pigment in the macular area that resembles the wings of a butterfly.
Martinique crinkled retinal pigment epitheliopathy
A form of retinal patterned dystrophy, characterized by retinal pigment epithelium and Bruch's membrane changes resembling a 'dry desert land'. It begins around the age of 30 and progresses to retinitis pigmentosa. MDPT3 inheritance is autosomal dominant.
An autosomal dominant retinal disease characterized by dyschromatopsia, gradual progressive loss of central visual acuity, and bilateral annular atrophy of retinal pigment epithelium at the macula.
An autosomal dominant retinal disease characterized by late-onset macular degeneration, with multiple drusen-like deposits, macular geographic atrophy, and choroidal neovascularization. Patients also exhibit extensive retinal dysfunction with impaired rod function.
Best vitelliform macular dystrophy, multifocal
Early-onset vitelliform macular dystrophy
Juvenile-onset vitelliform macular dystrophy
Macular degeneration, polymorphic vitelline
An autosomal dominant form of macular degeneration that usually begins in childhood or adolescence. VMD2 is characterized by typical 'egg-yolk' macular lesions due to abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. Progression of the disease leads to destruction of the retinal pigment epithelium and vision loss.
Adult-onset vitelliform macular dystrophy
Foveomacular dystrophy, adult-onset, with or without choroidal neovascularization
A form of vitelliform macular dystrophy, a retinal disease characterized by yellow, lipofuscin-containing deposits, usually localized at the center of the macula. Patients usually become symptomatic in the fourth or fifth decade of life with a protracted disease of decreased visual acuity.
A form of macular dystrophy, a retinal disease in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea. Vitelliform macular dystrophies are characterized by yellow, lipofuscin-containing deposits, usually localized at the center of the macula. VMD4 features include late-onset moderate visual impairment, small satellite drusen-like lesions in the foveal area, and preservation of retinal pigment epithelium reflectivity.
A form of macular dystrophy, a retinal disease in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea. Vitelliform macular dystrophies are characterized by yellow, lipofuscin-containing deposits, usually localized at the center of the macula. VMD5 features include late-onset moderate visual impairment and preservation of retinal pigment epithelium reflectivity.
A mild maculopathy characterized by full-field electroretinogram responses within normal limits, normal color vision, elevation of the photoreceptor layer in the foveal region and mild nuclear sclerosis.
Alpha-cell hyperplasia with glucagonemia
An autosomal recessive disorder characterized by alpha-cell hyperplasia of the pancreas, hyperglucagonemia without glucagonoma syndrome, aminoacidemia, and occasional hypoglycemia. The disease may lead to glucagonomas and/or primitive neuroectodermal tumors.
Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia and neutrophilic dermatosis
An autosomal recessive syndrome characterized by chronic recurrent multifocal osteomyelitis that is of early onset with a lifelong course, congenital dyserythropoietic anemia that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion-dependent, and transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration).
A major psychiatric disorder that is characterized by severe mood swings, with fluctuation between two abnormal mood states (manic or major depressive episode). Mania is accompanied by symptoms of euphoria, irritability, or excitation, whereas depression is associated with low mood and decreased motivation and energy.
A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning.
Keratosis palmoplantaris transgradiens of Siemens
A rare autosomal recessive skin disorder, characterized by diffuse transgressive palmoplantar keratoderma with keratotic lesions extending onto the dorsa of the hands and the feet (transgrediens). Patients may have hyperhidrosis. Other features include perioral erythema, lichenoid plaques on the knees and the elbows, and nail abnormalities.
An autosomal dominant syndrome characterized by overgrowth, advanced bone age, macrocephaly, impaired intellectual development, behavior anomalies, and dysmorphic facial features. Patients develop marfanoid habitus, with long and slender body, very low body mass, long narrow face, and arachnodactyly.
Male pseudohermaphrodism with gynecomastia
17-beta hydroxysteroid dehydrogenase III deficiency
17-ketosteroid reductase deficiency of testis
Neutral 17-beta-hydroxysteroid oxidoreductase deficiency
Pseudohermaphroditism, male, with gynecomastia
An autosomal recessive disorder that manifests, in males, as undermasculinization characterized by hypoplastic-to-normal internal genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory ducts) but female external genitalia and the absence of a prostate. This phenotype is caused by inadequate testicular synthesis of testosterone, which, in turn, results in insufficient formation of dihydrotestosterone in the anlage of the external genitalia and prostate during fetal development. At the expected time of puberty, there is a marked increase in plasma leuteinizing hormone and, consequently, in testicular secretion of androstenedione. Hence, a diagnostic hallmark of this disorder is a decreased plasma testosterone-to-androstenedione ratio. Significant amounts of the circulating androstenedione are, however, converted to testosterone, in peripheral tissues, thereby causing virilization.
An autosomal recessive inborn error of metabolism characterized by mild elevations in succinylacetone in blood and urine, usually identified by newborn screening. Liver function and coagulation are normal. MAAID is a benign disorder.
Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively).
Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants.
Autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria.
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome
An autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, metabolic abnormalities including insulin resistance and diabetes mellitus, sclerodermatous skin, and a facial appearance characterized by mandibular hypoplasia. Sensorineural deafness occurs late in the first or second decades of life.
Mandibuloacral dysplasia progeroid syndrome
A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MDPS is an autosomal recessive disorder. Clinical features include poor growth, osteoporosis, osteopenia, acroosteolysis of distal phalanges, arterial calcification, renal glomerulosclerosis and severe hypertension.
Mandibuloacral dysplasia with type A lipodystrophy
Lipodystrophy type A associated with mandibuloacral dysplasia
Mandibuloacral dysplasia with type A lipodystrophy atypical
Tendinous calcinosis arthropathy and progeroid features
A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MADA is an autosomal recessive disease characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroid appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.
Mandibuloacral dysplasia with type B lipodystrophy
Lipodystrophy type B associated with mandibuloacral dysplasia
A form of mandibuloacral dysplasia, a rare progeroid disorder with clinical and genetic heterogeneity, characterized by growth retardation, craniofacial dysmorphic features due to distal bone resorption, musculoskeletal and skin abnormalities associated with lipodystrophy. MADB is a disease characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, joint contractures, and generalized lipodystrophy with loss of subcutaneous fat from the extremities, face, neck and trunk.
Mandibulofacial dysostosis with alopecia
A form of mandibulofacial dysostosis, a disorder characterized by malar and mandibular hypoplasia, typically associated with abnormalities of the ears and eyelids. MFDA features include maxillary dysmorphism with dysplastic zygomatic arch, hypoplastic mandible, scalp alopecia, scant eyebrows and eyelashes, severe hypoplasia or aplasia of eyelids, small cupped dysplastic ears, conductive hearing loss, cleft palate, dental anomalies, micrognathia, and limited jaw mobility.
Mandibulofacial dysostosis with microcephaly
A rare syndrome characterized by progressive microcephaly, midface and malar hypoplasia, micrognathia, microtia, dysplastic ears, preauricular skin tags, significant developmental delay, and speech delay. Many patients have major sequelae, including choanal atresia that results in respiratory difficulties, conductive hearing loss, and cleft palate.
A rare condition defined by eyelid colobomas, cryptophthalmos, and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis.
Lysosomal alpha-D-mannosidase deficiency
A lysosomal storage disease characterized by accumulation of unbranched oligosaccharide chains. This accumulation is expressed histologically as cytoplasmic vacuolation predominantly in the CNS and parenchymatous organs. Depending on the clinical findings at the age of onset, a severe infantile (type I) and a mild juvenile (type II) form of alpha-mannosidosis are recognized. There is considerable variation in the clinical expression with intellectual disability, recurrent infections, impaired hearing and Hurler-like skeletal changes being the most consistent abnormalities.
An autosomal recessive lysosomal storage disease of glycoprotein catabolism. Clinical features are heterogeneous with a wide range of symptoms and age of onset. The disease is associated with a range of neurological involvement, including various degrees of intellectual disability in most of the cases, hearing loss and speech impairment, hypotonia, epilepsy and peripheral neuropathy. Affected individuals have a profound reduction in beta A mannosidase activity in plasma, fibroblasts and leukocytes.
Branched-chain alpha-keto acid dehydrogenase deficiency
Thiamine-responsive maple syrup urine disease
A metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated.
A mild form of maple syrup urine disease, a metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated. MSUDMV is characterized by increased plasma levels of branched-chain amino acids (BCAA) apparent at birth. Treatment with a low-protein diet free of BCAA can result in normal psychomotor development and lack of metabolic episodes.
An autosomal dominant syndrome characterized by progeria-like appearance with little subcutaneous fat and triangular facies, growth retardation, short stature, hypoplastic mandible crowded with unerupted supernumerary teeth, and cerebellar intention tremor.
Marbach-Schaaf neurodevelopmental syndrome
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, speech delay, behavioral abnormalities, hypotonia, and movement disorders including dyspraxia, apraxia, and clumsiness. More variable features include high pain tolerance, sleep disturbances, and variable non-specific dysmorphic features.
A syndrome characterized by a mask-like face with blepharophimosis, micrognathia, cleft or high-arched palate, low-set ears, congenital joint contractures, kyphoscoliosis, pectus excavatum or carinatum, and arachnodactyly. Additional features include decreased muscular mass, failure to thrive, renal anomalies, hypoplastic corpus callosum, cerebellar vermis hypoplasia, enlarged cisterna magna, and psychomotor retardation.
A hereditary disorder of connective tissue that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with Marfan syndrome, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in most of the patients and is almost always bilateral. The leading cause of premature death is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. Neonatal Marfan syndrome is the most severe form resulting in death from cardiorespiratory failure in the first few years of life.
Marfanoid-progeroid-lipodystrophy syndrome
An autosomal dominant syndrome characterized by congenital lipodystrophy, a progeroid facial appearance due to lack of subcutaneous fat, and variable signs of Marfan syndrome. Clinical features include premature birth with an accelerated linear growth disproportionate to the weight gain, ectopia lentis, aortic dilatation, dural ectasia, and arachnodactyly. Mental and motor development are within normal limits.
Autosomal recessive multisystem disorder which is characterized by cerebellar ataxia due to cerebellar atrophy, with Purkinje and granule cell loss and myopathy featuring marked muscle replacement with fat and connective tissue. Other cardinal features include bilateral cataracts, hypergonadotrophic hypogonadism and mild to severe intellectual disability. Skeletal abnormalities, short stature, dysarthria, strabismus and nystagmus are also frequent findings. Mutational inactivation of this protein may result in ER stress-induced cell death signaling or malfunctioning chaperone machineries that mishandle client proteins which are critical for the organs targeted in MSS.
An autosomal dominant disorder characterized by ocular abnormalities, deafness, craniofacial anomalies, and anhidrotic ectodermal dysplasia. Clinical features include short stature; flat or retruded midface with short, depressed nose, flat nasal bridge and anteverted nares; cleft palate with or without the Pierre Robin sequence; appearance of large eyes with ocular hypertelorism; cataracts, either congenital or juvenile; esotropia; high myopia; sensorineural hearing loss; spondyloepiphyseal abnormalities; calcification of the falx cerebri; ectodermal abnormalities, including defects in sweating and dental structures.
A distinct malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, intellectual disability, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia. Additional skeletal findings include long and thin tubular bones, broad middle phalanges with relatively narrow distal phalanges, and scoliosis. Inheritance is autosomal dominant.
Congenital analgesia, autosomal dominant
Insensitivity to pain, congenital, autosomal dominant
An autosomal dominant disorder characterized by congenital pain insensitivity. Painless cutaneous thermal burns and bone fractures are present in affected individuals. Corneal reflex is absent, sweating is decreased or absent. Patients have normal cognitive abilities, and display no evidence of distal weakness.
A rare neurodevelopmental disorder characterized by intellectual disability, sensorineural hearing loss, short stature and craniofacial dysmorphisms. Patients also exhibit abnormal teeth, widely spaced nipples, abnormal dermatoglyphics, renal insufficiency, and impaired haematopoiesis.
An autosomal recessive disease characterized by congenital cataracts, intellectual disability, and hypogonadism.
An autosomal recessive disorder characterized by congenital cataracts, mildly to severely impaired intellectual development, and facial dysmorphism. Other features include brain malformations, microcephaly, and hypogonadism-hypogenitalism.
Corpus callosum hypoplasia-psychomotor retardation, adducted thumbs-spastic paraparesis-hydrocephalus
An X-linked recessive syndrome with a highly variable clinical spectrum. Main clinical features include spasticity and hyperreflexia of lower limbs, shuffling gait, intellectual disability, aphasia and adducted thumbs. The features of spasticity have been referred to as complicated spastic paraplegia type 1 (SPG1). Some patients manifest corpus callosum hypoplasia and hydrocephalus. Inter- and intrafamilial variability is very wide, such that patients with hydrocephalus, MASA, SPG1, and agenesis of corpus callosum can be present within the same family.
Defect in lectin complement activation pathway, 2
A disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.
A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign.
Mastocytosis with associated hematologic disorder
A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality.
Severe maternal illness occurring during pregnancies with affected fetuses. This disease is associated with LCHAD deficiency and characterized by sudden unexplained infant death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome).
A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Maturity-onset diabetes of the young, type 13
Maturity-onset diabetes of the young, type 14
Maturity-onset diabetes of the young 8 with exocrine dysfunction
Diabetes and pancreatic exocrine dysfunction syndrome
An autosomal dominant form of diabetes characterized by a primary defect in insulin secretion, exocrine pancreatic dysfunction, altered pancreatic morphology, recurrent abdominal pain, and fecal elastase deficiency. Disease onset is at less than 25 years of age.
Characterized by polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The mutations producing MAS lead to constitutive activation of GS alpha.
Autosomal recessive developmental disorder. It is characterized by hydrometrocolpos, postaxial polydactyly and congenital heart defects.
McLeod syndrome with chronic granulomatous disease
A multisystem disorder characterized by the absence of red blood cell Kx antigen, weak expression of Kell red blood cell antigens, acanthocytosis, and compensated hemolysis. Most carriers of this McLeod blood group phenotype have acanthocytosis and elevated serum creatine kinase levels and are prone to develop a severe neurologic disorder resembling Huntington disease. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy.
Rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities.
A disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.
A form of Meckel syndrome, a disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.
A form of Meckel syndrome, an autosomal recessive disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. Death occurs in the prenatal or perinatal period.
A condition characterized by intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium. Meconium ileus is a known clinical manifestation of cystic fibrosis.
Erythrokeratodermia variabilis Kamouraska type
Impaired intellectual development, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma
A disorder characterized by erythematous skin lesions and hyperkeratosis, severe psychomotor retardation, peripheral neuropathy, sensorineural hearing loss, together with elevated very-long-chain fatty acids and severe congenital diarrhea.
Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation.
Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.
An X-linked, thoracic aortic aneurysm syndrome characterized by early-onset, severe aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia.
Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations
An autosomal dominant neurodevelopmental disorder with onset in infancy. MCCCHCM is characterized by global developmental delay, impaired intellectual development, poor or absent speech, unsteady gait, ataxia, inability to walk, and variable brain abnormalities. Seizures and autistic features are observed in some patients. Brain imaging findings include an enlarged corpus callosum in the absence of megalencephaly, cerebellar hypoplasia, ventricular dilation, gyral abnormalities, and cortical malformations.
An autosomal dominant congenital anomaly characterized by a massively dilated urinary bladder with disrupted smooth muscle in the bladder wall. MGBL is a sex-limited trait with 95% male predominance, and incomplete penetrance. Affected males frequently die in utero.
Megacystis-microcolon-intestinal hypoperistalsis syndrome
A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS inheritance is autosomal recessive.
Megacystis-microcolon-intestinal hypoperistalsis syndrome 2
A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS2 inheritance is autosomal recessive.
Megacystis-microcolon-intestinal hypoperistalsis syndrome 3
A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS3 inheritance is autosomal recessive.
Megacystis-microcolon-intestinal hypoperistalsis syndrome 4
A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS4 inheritance is autosomal recessive.
Megacystis-microcolon-intestinal hypoperistalsis syndrome 5
A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS5 is an autosomal dominant form with significant inter- and intrafamilial variability.
Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without impaired intellectual development
Leukoencephalopathy, megalencephalic, with subcortical cysts, 2B
A neurodegenerative disorder characterized by infantile-onset of macrocephaly and mildly delayed motor development associated with white-matter abnormalities on brain magnetic resonance imaging. The phenotype is milder that MLC2A, with better preserved cerebellar white matter and no subcortical cysts outside the temporal region. On follow-up, patients show normal or almost normal motor function. Some patients have normal intelligence, whereas others have a significant cognitive deficiency.
Megalencephaly-capillary malformation-polymicrogyria syndrome
Macrocephaly-cutis marmorata telangiectatica congenita
Megalencephaly-capillary malformation syndrome
Megalencephaly-cutis marmorata telangiectatica congenita
A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria.
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
Megalencephaly mega corpus callosum and complete lack of motor development
Megalencephaly-polymicrogyria-mega corpus callosum syndrome
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome
A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3
A syndrome characterized by megalencephaly, ventriculomegaly that may lead to hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
Megaloblastic anemia due to dihydrofolate reductase deficiency
An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.
An autosomal recessive metabolic disorder characterized by megaloblastic anemia resulting from decreased folate transport into erythrocytes. Disease manifestations include hemolytic anemia, hyperhomocysteinemia, and low vitamin B12. Serum folate levels are normal, but erythrocyte folate levels are decreased. Treatment with oral folate corrects the anemia and normalizes homocysteine.
An eye disorder in which the corneal diameter is bilaterally enlarged (greater than 13 mm) without an increase in intraocular pressure. It may also be referred to as anterior megalophthalmos, since the entire anterior segment is larger than normal. Features of megalocornea in addition to a deep anterior chamber include astigmatic refractive errors, atrophy of the iris stroma, miosis secondary to decreased function of the dilator muscle, iridodonesis, and tremulousness, subluxation, or dislocation of the lens. Whereas most affected individuals exhibit normal ocular function, complications include cataract development and glaucoma following lenticular dislocation or subluxation.
An X-linked recessive syndrome characterized by intellectual disability, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity.
Microtia absent patellae micrognathia syndrome
A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.
A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.
A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. MGORS7 inheritance is autosomal recessive.
A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. MGORS8 inheritance is autosomal recessive.
A syndrome characterized by congenital pigmentary skin lesions which can occur at any site and can cover most of the body surface. These lesions may or may not be hairy. Congenital melanocytic nevi are associated with neuromelanosis (the presence of melanin-producing cells within the brain parenchyma or leptomeninges). Less commonly they are associated with malignant melanoma in childhood, both in the skin and the central nervous system. CMNS patients also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip.
A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites.
Susceptibility to melanoma and renal cell carcinoma
Most common intraocular malignancy, arising from melanocytes in the iris, ciliary body, or choroid. Metastases develop in more than 30% of case patients, almost invariably in the liver, with poor prognosis.
Characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.
A rare congenital disease characterized by the presence of giant or multiple melanocytic nevi on the skin, foci of melanin-producing cells within the brain parenchyma, and infiltration of leptomeninges by abnormal melanin deposits. Neurologic abnormalities include seizures, hydrocephalus, arachnoid cysts, tumors, and syringomyelia. Some patients may develop malignant melanoma.
Severe congenital bone disorder characterized by typical facies (exophthalmos, full cheeks, micrognathia and malalignment of teeth), flaring of the metaphyses of long bones, s-like curvature of bones of legs, irregular constrictions in the ribs, and sclerosis of base of skull.
A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma.
Male EBP disorder with neurological defects
An X-linked recessive disorder associated with a defect in sterol biosynthesis. Disease manifestations and severity are highly variable. Clinical features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities.
A common neoplasm of the central nervous system derived from arachnoidal cells. The majority of meningiomas are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Most cases are sporadic. Familial occurrence of meningioma is rare.
A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum.
An X-linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes. A mild form of the disease has been described, in which cerebellar ataxia and moderate developmental delay predominate.
Merosin-deficient congenital muscular dystrophy 1A
Characterized by difficulty walking, hypotonia, proximal weakness, hyporeflexia, and white matter hypodensity on MRI.
An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.
Metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
An autosomal recessive disorder characterized by metabolic encephalomyopathic crises, hypoglycemia, hyperammonemia, episodic rhabdomyolysis, susceptibility to life-threatening cardiac tachyarrhythmias, developmental delay, intellectual disability, and mild diffuse cerebral atrophy.
Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression
An autosomal recessive disease characterized by muscle weakness, developmental delay, lactic acidosis, and encephalopathy. The severity of the clinical manifestations is highly variable even within affected individuals of the same family, ranging from asymptomatic lactic acidosis to severe developmental regression, epilepsy, intellectual disability, metabolic crisis, and multiorgan involvement.
A rare congenital malformation of the hand characterized by the partial or complete fusion of the fourth and fifth metacarpals. The anomaly occurs as an isolated trait or part of a syndrome.
A skeletal disorder with radiologic features of both multiple exostoses and Ollier disease, characterized by the presence of exostoses, commonly of the bones of the hands and feet, and enchondromas of the metaphyses of long bones and iliac crest.
Cerebral sclerosis, diffuse, metachromatic form
Metachromatic leukodystrophy, late infantile
An autosomal recessive disease caused by abnormal intralysosomal accumulation of cerebroside-3-sulfate in central and peripheral nervous systems, as well as other organs. MLD is clinically characterized by leukodystrophy, progressive demyelination and a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Decreased arylsulfatase A activity is detected in urine, leukocytes, and fibroblasts of affected individuals. Several forms of the disease can be distinguished according to the age at onset and disease severity: late infantile, juvenile and adult forms, partial cerebroside sulfate deficiency, and pseudoarylsulfatase A deficiency. Individuals with pseudoarylsulfatase A deficiency have low arylsulfatase A activity but lack neurological manifestations and are apparently healthy.
Metachromatic leukodystrophy due to saposin B deficiency
Metachromatic leukodystrophy due to cerebroside sulfatase activator deficiency
A form of metachromatic leukodystrophy biochemically characterized by tissue accumulation of cerebroside-3-sulfate, saposin B deficiency, and normal arylsulfatase A activity. Clinical manifestations include periventricular white matter abnormalities, demyelination, and peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis.
A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
Metaphyseal chondrodysplasia, Jansen type
Metaphyseal chondrodysplasia, Murk Jansen type
A rare autosomal dominant disorder characterized by a short-limbed dwarfism associated with hypercalcemia and normal or low serum concentrations of the two parathyroid hormones.
Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly
An autosomal dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth.
Metaphyseal chondrodysplasia, Spahr type
An autosomal recessive, rare disease characterized by moderate short stature, mild genua vara, and radiographic signs of metaphyseal dysplasia, but no biochemical signs of rickets.
A severe spondyloepimetaphyseal dysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis. Radiologic features include severe platyspondyly, severe metaphyseal enlargement and shortening of long bones.
Methemoglobinemia and ambiguous genitalia
Methemoglobinemia due to deficiency of cytochrome b5
An autosomal recessive disorder characterized by sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve, male undermasculinization, absent or disturbed pubertal development, decreased levels of erythrocyte cytochrome B5, and excessive amounts of methemoglobin in blood cells resulting in cyanosis and hypoxia.
Methemoglobinemia congenital autosomal recessive
Methemoglobinemia due to deficiency of methemoglobin reductase
NADH-cytochrome b5 reductase deficiency type I
NADH-cytochrome b5 reductase deficiency type II
NADH-dependent methemoglobin reductase deficiency
A form of methemoglobinemia, a hematologic disease characterized by the presence of excessive amounts of methemoglobin in blood cells, resulting in decreased oxygen carrying capacity of the blood, cyanosis and hypoxia. There are two types of methemoglobinemia CYB5R3-related. In type 1, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type 2, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes and all body tissues. Type 2 methemoglobinemia is associated with mental deficiency and other neurologic symptoms.
Methionine adenosyltransferase deficiency
An inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic symptoms may be present in rare cases with severe loss of methionine adenosyltransferase activity.
Methylmalonate semialdehyde dehydrogenase deficiency
A metabolic disorder characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids.
Methylmalonic aciduria and homocystinuria type cblJ
A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include feeding difficulties, poor growth, hypotonia, lethargy, anemia, and developmental delay.
Methylmalonic aciduria and homocystinuria, cblC type
Methylmalonic acidemia and homocystinuria cblC type
Methylmalonic aciduria and homocystinuria vitamin B12-responsive
Vitamin B12 metabolic defect with combined deficiency of methylmalonyl-CoA mutase and homocysteine:methyltetrahydrofolate methyltransferase
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood.
Methylmalonic aciduria and homocystinuria, cblD type
Methylmalonic acidemia and homocystinuria cblD type
Methylmalonic aciduria and homocystinuria cblD-combined
Methylmalonic aciduria and homocystinuria cblD original
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include developmental delay, hyotonia, intellectual disability, seizures, megaloblastic anemia. Some patients manifest combined methylmalonic aciduria and homocystinuria (referred to as cblD original), some have only isolated homocystinuria (cblD variant 1), and others have only methylmalonic aciduria (cblD variant 2).
Methylmalonic aciduria and homocystinuria, cblF type
Methylmalonic acidemia and homocystinuria cblF type
Methylmalonic aciduria due to vitamin B12-release defect
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). It is due to accumulation of free cobalamin in lysosomes, thus hindering its conversion to cofactors. Clinical features include developmental delay, stomatitis, glossitis, seizures and methylmalonic aciduria responsive to vitamin B12.
Methylmalonic aciduria and homocystinuria, cblX type
Intellectual developmental disorder, X-linked 3
Methylmalonic aciduria and homocysteinemia , cblX type
An X-linked recessive metabolic disorder characterized by severely delayed psychomotor development apparent in infancy, failure to thrive, impaired intellectual development, and intractable epilepsy. Additional features may include microcephaly and choreoathetosis.
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
Methylmalonicaciduria due to methylmalonyl-CoA mutase deficiency
Methylmalonicaciduria vitamin B12 unresponsive
An often fatal disorder of organic acid metabolism. Common clinical features include lethargy, vomiting, failure to thrive, hypotonia, neurological deficit and early death. Two forms of the disease are distinguished by the presence (mut-) or absence (mut0) of residual enzyme activity. Mut0 patients have more severe neurological manifestations of the disease than do MUT- patients. MMAM is unresponsive to vitamin B12 therapy.
Vitamin B12 responsive methylmalonic acidemia type cbl A
Vitamin B12 responsive methylmalonic aciduria type cbl A
A disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin.
Vitamin B12 responsive methylmalonic acidemia type cbl B
Vitamin B12 responsive methylmalonic aciduria type cbl B
Methylmalonic aciduria, transient, due to transcobalamin receptor defect
Methylmalonic aciduria due to transcobalamin receptor defect
A metabolic disorder characterized by increased blood C3-acylcarnitine levels, elevated methylmalonate and homocysteine, and low uptake of transcobalamin-bound cobalamin, but normal conversion to adenosylcobalamin and methylcobalamin.
Autosomal recessive inborn error of amino acid metabolism, involving valine, threonine, isoleucine and methionine. This organic aciduria may present in the neonatal period with life-threatening metabolic acidosis, hyperammonemia, feeding difficulties, pancytopenia and coma.
Accumulation of mevalonic acid which causes a variety of symptoms such as psychomotor retardation, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, hypotonia, myopathy, and ataxia.
Microangiopathy and leukoencephalopathy, pontine, autosomal dominant
A form of cerebral small vessel disease characterized by the recurrence of ischemic strokes starting in the thirties or forties, and associated with progressive imbalance and cognitive impairment. MRI examination shows ischemic lacunas in the pons and cerebral hemispheres, and diffuse leukoencephalopathy affecting various brain regions.
Microcephalic osteodysplastic primordial dwarfism 2
Osteodysplastic primordial dwarfism type 2
Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence.
Microcephaly 1, primary, autosomal recessive
Premature chromosome condensation syndrome
A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. Some MCHP1 patients also present growth retardation, short stature, and misregulated chromosome condensation as indicated by a high number of prophase-like cells detected in routine cytogenetic preparations and poor-quality metaphase G-banding.
Microcephaly 10, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH10 is characterized by extremely small head size and death usually by 1 year of age. Neuropathologic examination shows severe loss of neurons as well as neuronal loss of polarity and abnormal dendritic maturation.
Microcephaly 11, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.
Microcephaly 12, primary, autosomal recessive
Microcephaly 13, primary, autosomal recessive
Microcephaly 14, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.
Microcephaly 16, primary, autosomal recessive
Microcephaly 17, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH17 is a severe form characterized by lissencephaly, enlarged ventricles, agenesis of the corpus callosum, cerebellar hypoplasia, and brainstem hypoplasia. Patients manifest delayed psychomotor development, intellectual disability, spasticity, axial hypotonia, and dysmorphic features.
Microcephaly 18, primary, autosomal dominant
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH18 affected individuals manifest microcephaly with mild to moderate intellectual disability.
Microcephaly 19, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH19 affected individuals manifest severe developmental delay, failure to thrive, cortical blindness, and spasticity. Brain imaging show a simplified gyral pattern, thin corpus callosum, slight ventricular dilation, and delayed myelination.
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations
A disease characterized by microcephaly, moderate to severe intellectual disability, and various type of cortical malformations in most patients. Microcephaly is defined as a head circumference more than 3 standard deviations below the age-related mean. Cortical malformations include pachygyria with cortical thickening, microgyria, lissencephaly, hypoplasia of the corpus callosum, schizencephaly. All affected individuals have delayed psychomotor development. Some patients have seizures.
Microcephaly 20, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH20 features include mild to moderate intellectual disability, autistic features, poor speech. Disease severity is highly variable.
Microcephaly 21, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH21 features include mild intellectual disability, intrauterine growth retardation, short stature, and microcephaly.
Microcephaly 22, primary, autosomal recessive
Microcephaly 23, primary, autosomal recessive
Microcephaly 24, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH24 patients additionally manifest mildly impaired intellectual development, cerebellar vermis hypoplasia, and fifth finger clinodactyly.
Microcephaly 25, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH25 patients additionally manifest global developmental delay, severe intellectual disability with speech impairment, attention deficit-hyperactivity disorder, and reduced white matter and thin corpus callosum on brain imaging.
Microcephaly 26, primary, autosomal dominant
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH26 is an autosomal dominant, progressive form apparent at birth or in early infancy. It is associated with relative short stature, variable severity of intellectual disability, and neurological features as the core symptoms. Brain imaging shows a simplified gyral pattern of the cortex and abnormal corpus callosum in some patients.
Microcephaly 27, primary, autosomal dominant
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH27 is an autosomal dominant form apparent in early childhood and associated with global developmental delay, delayed walking, inability to walk, impaired intellectual development, and poor or absent speech. Brain imaging may show enlarged ventricles or gyral abnormalities in some patients.
Microcephaly 28, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH28 is an autosomal recessive form characterized by reduced head size (down to -8 SD) and variably impaired intellectual development apparent from early childhood.
Microcephaly 29, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH29 is characterized by small head circumference apparent at birth and associated with global developmental delay, impaired intellectual development, speech delay, and behavioral abnormalities. Affected individuals also have poor overall growth with short stature, mild dysmorphic facial features, and seizures.
Microcephaly 3, primary, autosomal recessive
A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder.
Microcephaly 30, primary, autosomal recessive
A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH30 is characterized by small head, poor overall growth, and global developmental delay with variably impaired intellectual development. Affected individuals may also have variable congenital anomalies, including atrial septal defect, dysmorphic facial features, tracheal stenosis, and anomalies of the skin and teeth.
Microcephaly 4, primary, autosomal recessive
Microcephaly 5, primary, autosomal recessive
Microcephaly primary autosomal recessive 5 with simplified gyral pattern
Microcephaly 6, primary, autosomal recessive
Microcephaly 7, primary, autosomal recessive
Microcephaly 8, primary, autosomal recessive
Microcephaly 9, primary, autosomal recessive
Microcephaly and chorioretinopathy, autosomal recessive, 1
A syndrome characterized by microcephaly, cognitive impairment, underdeveloped retina and choroid, and epilepsy in some patients. The more anterior parts of the retina, near the periphery and pars plana, have a grayish hue and diminutive vasculature similar to retinopathy of prematurity. Visual impairment becomes evident during the first year of life.
Microcephaly and chorioretinopathy, autosomal recessive, 2
A severe disorder characterized by microcephaly, delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities.
Microcephaly and chorioretinopathy, autosomal recessive, 3
A disorder characterized by congenital microcephaly and chorioretinal dysplasia associated with poor vision and nystagmus. Variable ocular anomalies include microphthalmia, retinal folding, retinal detachment, optic nerve hypoplasia, absence of retinal vessels, round areas of chorioretinal atrophy, and attenuated electroretinogram. Most patients have mild developmental delay and mild learning difficulties.
Microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development
Lymphedema and retinal folds with microcephaly and microphthalmos
Lymphedema microcephaly chorioretinopathy syndrome
Microcephaly lymphedema chorioretinal dysplasia syndrome
An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.
A disorder characterized by severe congenital microcephaly and severe 2-ketoglutaric aciduria leading to death within the first year.
Microcephaly, cataracts, impaired intellectual development, and dystonia with abnormal striatum
An autosomal recessive syndrome characterized by cognitive impairment, attention deficit hyperactivity disorder, microcephaly, growth retardation, congenital cataract, and dystonia. Brain MRI shows unusual thinning of the lentiform nucleus, predominantly involving the putamen, and swelling in the caudate heads.
Microcephaly, congenital cataract, and psoriasiform dermatitis
An autosomal recessive inborn error of cholesterol metabolism characterized by accumulation of a large amount of methylsterols, particularly dimethylsterols, in affected individuals. Patients manifest psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay.
Microcephaly, developmental delay, and brittle hair syndrome
An autosomal recessive disorder characterized by developmental delay, motor and cognitive disabilities, brittle hair and nails, failure to thrive, and short stature.
Microcephaly, epilepsy, and diabetes syndrome 1
An autosomal recessive disorder characterized by microcephaly, simplified gyral pattern, severe epilepsy, and infantile diabetes.
Microcephaly, epilepsy, and diabetes syndrome 2
An autosomal recessive disorder characterized by neonatal or early-onset diabetes, severe microcephaly, and epilepsy.
Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome
An autosomal dominant syndrome characterized by primary microcephaly, ambiguous male genitalia, dysmorphic facies, polydactyly, and unilateral renal agenesis. Variable brain, cardiac, and skeletal anomalies are present, including corpus callosum agenesis or dysgenesis, lissencephaly, atrial and ventricular septal defects, patent ductus arteriosus, hypoplastic right ventricle, and joint contractures.
Microcephaly, growth deficiency, seizures, and brain malformations
An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency, microcephaly, facial dysmorphism, early-onset seizures, brain malformations such as partial agenesis of the corpus callosum and simplified gyration, and poor or absent psychomotor development.
Microcephaly, growth restriction, and increased sister chromatid exchange 2
An autosomal recessive disorder characterized by intrauterine growth restriction, poor postnatal growth with short stature and microcephaly, and increased sister chromatid exchange on cell studies.
Microcephaly, postnatal progressive, with seizures and brain atrophy
A disorder characterized by postnatal progressive microcephaly and severe developmental retardation associated with cerebral and cerebellar atrophy. Infants manifest swallowing difficulties leading to failure to thrive, jitteriness, poor visual fixation, truncal arching, seizures. There is no acquisition of developmental milestones and patients suffer from marked spasticity and profound retardation. Progressive microcephaly becomes evident few months after birth.
Microcephaly, progressive, with seizures and cerebral and cerebellar atrophy
A severe, autosomal recessive, neurodevelopmental and neurodegenerative disorder characterized by progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, resulting in profoundly delayed development and hypotonia.
Microcephaly, seizures, and developmental delay
Developmental and epileptic encephalopathy 10
Early infantile epileptic encephalopathy 10
An autosomal recessive neurodevelopmental disorder characterized by infantile-onset seizures, microcephaly, severe intellectual disability and delayed motor milestones with absent speech or only achieving a few words. Most patients also have behavioral problems with hyperactivity. Microcephaly is progressive and without neuronal migration or structural abnormalities, consistent with primary microcephaly.
Microcephaly, short stature, and impaired glucose metabolism 1
Microcephaly, short stature, and impaired glucose metabolism
An autosomal recessive disease characterized by microcephaly, intellectual disability, short stature, and disturbed glucose metabolism. Additional clinical features include delayed puberty, hypoglycemia-related seizures, hyperinsulinemic hypoglycemia, and early-onset diabetes.
Microcephaly, short stature, and impaired glucose metabolism 2
An autosomal recessive disease characterized by microcephaly, intellectual disability, short stature, and disturbed glucose metabolism.
Microcephaly, short stature, and limb abnormalities
An autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities mainly affecting the upper limb and radial ray. Mild intellectual disability and developmental delay is observed in some patients.
Microcephaly, short stature, and polymicrogyria with or without seizures
A disease characterized by many irregular small gyri in the brain surface and fusion of the molecular layer over multiple small gyri, which gives a festooned appearance to the cortical surface, without abnormal neuronal migration. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. MSSP patients have moderate to severe intellectual disability, poor speech, dysarthria and seizures.
Microcephaly-capillary malformation syndrome
A congenital disorder characterized by severe progressive microcephaly, early-onset refractory epilepsy, profound developmental delay, and multiple small capillary malformations spread diffusely on the body. Additional more variable features include dysmorphic facial features, distal limb abnormalities, and mild heart defects.
A severe autosomal recessive disorder characterized by intrauterine growth restriction, marked microcephaly, craniofacial anomalies, skeletal dysplasia, and variable malformations of the limbs, particularly the upper limbs. It usually results in death in utero or in the perinatal period.
Microcornea, myopic chorioretinal atrophy, and telecanthus
A ocular syndrome characterized by microcornea and myopic chorioretinal atrophy. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. In addition to ocular findings, some patients have telecanthus and posteriorly rotated ears.
Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 1
An autosomal dominant ocular disorder characterized by poor visual acuity in early childhood, due to congenital cataract and microcornea followed by rod-cone dystrophy, with later development of posterior staphyloma.
A severe neurodevelopmental disorder characterized by microcephaly, severe motor and intellectual disability, spasticity, and brain malformations that include gross dilation of the ventricles with complete absence of the cerebral hemispheres or severe delay in their development.
A disease trait defined as a stretched penile length of less than 2.5 standard deviations below the mean for age. Traditionally, the term micropenis refers to a penis that is otherwise normally formed. The term microphallus is used when associated hypospadias is present. The mean stretched penile length in a full-term newborn male is 3.5 cm. Measurements of less than 2-2.5 cm in a full-term newborn male meet the definition of micropenis.
Microphthalmia with cataracts and iris abnormalities
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, cataract and other abnormalities like cataract may also be present.
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
Posterior microphthalmia with retinitis pigmentosa, foveoschisis and optic disk drusen
A disorder characterized by posterior microphthalmia, retinitis pigmentosa, foveoschisis and optic disk drusen. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present.
Autosomal recessive posterior microphthalmos
A developmental ocular disorder characterized by small malformed eyes. Clinical features are extreme hyperopia due to short axial length with essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses, and thickened scleral wall. Palpebral fissures appear narrow because of relatively deep-set eyes, visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical disks, tortuous vessels, and an abnormal foveal avascular zone.
Microphthalmia, isolated, with coloboma, 10
A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
Microphthalmia, isolated, with coloboma, 3
Microphthalmia, isolated, with coloboma, 5
Microphthalmia, isolated, with coloboma, 6
Microphthalmia, isolated, with coloboma, 7
Microphthalmia, isolated, with coloboma, 8
Microphthalmia, isolated, with coloboma, 9
An autosomal recessive disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Some patients exhibit developmental delay and intellectual disability or autism.
Microphthalmia or anophthalmos with associated anomalies
A rare syndrome defined by the canonical features of unilateral or bilateral microphthalmia or anophthalmia and defects in the skeletal and genitourinary systems. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. Anomalies of the digits, teeth, and ears are hallmarks of MCOPS1. Intellectual disability ranges from mild to severe, with self-mutilating behaviors and seizures in severely affected MCOPS1 individuals.
Microphthalmia with corpus callosum agenesis and orofacial clefting
A rare clinical entity including as main characteristics microphthalmia and small optic nerves, cleft lip and palate, absence of corpus callosum, hippocampal malformations, and absence of the pineal gland. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Microphthalmia with or without pulmonary hypoplasia, diaphragmatic hernia, and/or cardiac defects
A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities.
Colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation
A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS13 patients exhibit colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation.
Microphthalmia and/or coloboma with developmental delay
A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS15 is characterized by microphthalmia and/or coloboma, with developmental delay in which speech appears to be more severely affected than motor abilities. Additional ocular anomalies that have been observed include ptosis, keyhole-shaped pupils, microcornea, sclerocornea, and anterior segment dysgenesis.
Microphthalmia, cataracts, radiculomegaly and septal heart defects
A very rare multiple congenital anomaly syndrome characterized by eye anomalies (congenital cataract, microphthalmia, or secondary glaucoma), facial abnormalities (long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, or submucous cleft palate), cardiac anomalies (atrial septal defect, ventricular septal defect, or floppy mitral valve) and dental abnormalities (canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, or variable root length). Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Anophthalmia/microphthalmia-esophageal atresia
Anophthalmia-esophageal-genital syndrome
Microphthalmia and esophageal atresia syndrome
A disease characterized by the rare association of malformations including uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with trachoesophageal fistula. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Patients manifest unilateral or bilateral microphthalmia/clinical anophthalmia and variable additional features including pituitary dysfunction, coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or agenesis of the optic nerve, agenesis of the corpus callosum, developmental delay, joint laxity, hypotonia, and seizures. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Clinical anophthalmia with micrognathia, malformed ears, digital anomalies and abnormal external genitalia
Microphthalmia with brain and digit developmental anomalies
A disease characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Microcephaly, microphthalmia, ectrodactyly of lower limbs and prognathism
A very rare congenital syndrome characterized by microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Anophthalmia, clinical, with mild facial dysmorphism and variable malformations of the lung, heart, and diaphragm
Anophthalmia/microphthalmia and pulmonary hypoplasia
Pulmonary agenesis, microphthalmia, and diaphragmatic defect
Pulmonary hypoplasia-diaphragmatic hernia-anophthalmia-cardiac defect
A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Microphthalmia/coloboma and skeletal dysplasia syndrome
Microphthalmia and/or coloboma, with or without rhizomelic skeletal dysplasia
A disease characterized by bilateral colobomatous microphthalmia or bilateral anophthalmia, associated with skeletal dysplasia in some cases. Additional ocular findings include microcornea, cataracts, corectopia and nystagmus. Intellectual disability is present in some patients.
Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma
A rare disease characterized by smaller and more spherical lenses than normal bilaterally, an increased anteroposterior thickness of the lens, and highly myopic eyes. Lens dislocation or subluxation may occur, leading to defective accommodation.
Microtia with or without hearing impairment
Microtia is a congenital deformity of the outer ear that is small and abnormally shaped. In classic microtia, the pinna is essentially absent, except for a vertical sausage-shaped skin remnant. The superior aspect of this sausage-shaped skin remnant consists of underlying unorganized cartilage, and the inferior aspect of this remnant consists of a relatively well-formed lobule.
Microtia, hearing impairment, and cleft palate
A disease characterized by microtia, mixed symmetric severe to profound hearing impairment, and partial cleft palate. Microtia is a congenital deformity of the outer ear that is small and abnormally shaped. In classic microtia, the pinna is essentially absent, except for a vertical sausage-shaped skin remnant. The superior aspect of this sausage-shaped skin remnant consists of underlying unorganized cartilage, and the inferior aspect of this remnant consists of a relatively well-formed lobule. Syndromic forms of microtia occur in conjunction with other abnormalities including cleft palate, a congenital fissure of the soft and/or hard palate due to faulty fusion.
Microvascular complications of diabetes 1
Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
Microvascular complications of diabetes 2
Microvascular complications of diabetes 3
Microvascular complications of diabetes 4
Microvascular complications of diabetes 5
Microvascular complications of diabetes 6
Microvascular complications of diabetes 7
Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
An X-linked recessive disorder with onset in early childhood, characterized by midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis. Variable clinical features include anemia, and mild early motor or speech delay.
A form of migraine transmitted in an autosomal dominant pattern. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
Migraine familial hemiplegic with progressive cerebellar ataxia
A subtype of migraine with aura associated with ictal hemiparesis and, in some families, cerebellar ataxia and atrophy. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
A subtype of migraine with aura associated with hemiparesis in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
A subtype of migraine associated with transient blindness in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
A contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly and distinct facial features. Additional congenital malformations can be part of the condition.
Myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy
A form of syndromic adrenal hypoplasia characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy.
Mirror movements 1 and/or agenesis of the corpus callosum
A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. Some MRMV1 patients have agenesis of the corpus callosum.
A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.
A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities. MRMV4 inheritance is autosomal dominant.
Constitutional mismatch repair deficiency syndrome
An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer.
A disorder characterized by episodic demyelination, sensorimotor polyneuropathy, and sensorineural hearing loss.
Diabetes neonatal with pancreatic hypoplasia intestinal atresia and gallbladder aplasia or hypoplasia
A disorder characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder. There is no dysmorphic features.
Mitochondrial complex I deficiency, mitochondrial type 1
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
Mitochondrial complex I deficiency, nuclear type 1
Complex I mitochondrial respiratory chain deficiency
Deficiency of mitochondrial NADH dehydrogenase component of complex I
NADH:Ubiquinone oxidoreductase deficiency
Mitochondrial complex I deficiency, nuclear type 10
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN10 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 11
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN11 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 12
Mitochondrial complex I deficiency, nuclear type 13
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN13 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 14
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN14 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 15
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN15 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 16
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN16 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 17
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN17 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 18
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN18 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 19
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN19 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 2
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN2 inheritance is autosomal recessive.
Mitochondrial complex I deficiency, nuclear type 20
Acyl-CoA dehydrogenase family, member 9, deficiency
Mitochondrial complex I deficiency due to ACAD9 deficiency
An autosomal recessive metabolic disorder associated with mitochondrial complex I deficiency, resulting in multisystemic and variable manifestations. Clinical features include infantile onset of acute metabolic acidosis, Reye-like episodes (brain edema and vomiting that may rapidly progress to seizures, coma and death), exercise intolerance, hypertrophic cardiomyopathy, liver failure, muscle weakness, and neurologic dysfunction.
Mitochondrial complex I deficiency, nuclear type 21
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN21 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 22
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN22 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 23
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN23 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 24
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN24 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 25
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN25 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 26
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN26 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 27
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN27 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 28
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN28 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 29
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN29 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 3
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN3 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 30
Mitochondrial complex I deficiency, nuclear type 31
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN31 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 32
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN32 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 33
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN33 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 34
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN34 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 35
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN35 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 36
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN36 is characterized by global developmental delay, hypotonia, and failure to thrive apparent from infancy or early childhood. Affected individuals usually do not acquire ambulation, show progressive spasticity, and have impaired intellectual development with absent speech. MC1DN36 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 37
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN37 features include developmental delay, cerebral atrophy, epilepsy, growth retardation, congenital myopathy with disproportion of fibers, and severely decreased activity of complex I. MC1DN37 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 39
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN39 is an autosomal recessive form characterized by intrauterine growth retardation, anemia, and postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with a fatal outcome.
Mitochondrial complex I deficiency, nuclear type 4
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN4 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 5
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN5 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 6
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN6 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 7
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN7 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 8
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN8 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex I deficiency, nuclear type 9
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN9 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial complex II deficiency, nuclear type 1
Complex 2 mitochondrial respiratory chain deficiency
Complex II mitochondrial respiratory chain deficiency
SDH-defective infantile leukoencephalopathy
A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN1 inheritance is autosomal recessive.
Mitochondrial complex II deficiency, nuclear type 2
A form of mitochondrial complex II deficiency, a disorder with heterogeneous clinical manifestations. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN2 inheritance is autosomal recessive.
Mitochondrial complex II deficiency, nuclear type 3
A form of mitochondrial complex II deficiency, a disorder with heterogeneous clinical manifestations. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN3 inheritance is autosomal recessive.
Mitochondrial complex II deficiency, nuclear type 4
A form of mitochondrial complex II deficiency, a disorder with heterogeneous clinical manifestations. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN4 is a severe, autosomal recessive form characterized by early-onset progressive neurodegeneration with leukoencephalopathy.
Mitochondrial complex III deficiency, nuclear type 1
Complex 3 mitochondrial respiratory chain deficiency
Complex III mitochondrial respiratory chain deficiency
A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance.
Mitochondrial complex III deficiency, nuclear type 10
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. MC3DN10 is an autosomal recessive form characterized by fetal bradycardia, poor feeding, hypotonia, hypertrophic cardiomyopathy, alopecia totalis, low mitochondrial complex III activity and lactic acidosis.
Mitochondrial complex III deficiency, nuclear type 11
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. MC3DN11 is an autosomal recessive form characterized by recurrent episodes of severe lactic acidosis, hyperammonemia, hypoglycemia, and encephalopathy.
Mitochondrial complex III deficiency, nuclear type 2
Mitochondrial complex III deficiency, nuclear type 3
Mitochondrial complex III deficiency, nuclear type 4
Mitochondrial complex III deficiency, nuclear type 5
Mitochondrial complex III deficiency, nuclear type 6
An autosomal recessive disorder caused by mitochondrial dysfunction. It is characterized by onset in early childhood of episodic acute lactic acidosis, ketoacidosis, and insulin-responsive hyperglycemia, usually associated with infection. Laboratory studies show decreased activity of mitochondrial complex III. Psychomotor development is normal.
Mitochondrial complex III deficiency, nuclear type 7
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. MC3DN7 is characterized by severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction. Additional clinical features include a dysmorphic facial appearance, delayed psychomotor development, autistic features, aggressive behavior, and mild sensorineural hearing loss.
Mitochondrial complex III deficiency, nuclear type 8
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance.
Mitochondrial complex III deficiency, nuclear type 9
A form of mitochondrial complex III deficiency, a disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. MC3DN9 clinical features include feeding difficulties, hypoglycemia, severe lactic acidosis, and delayed psychomotor development.
Complex 4 mitochondrial respiratory chain deficiency
Complex IV mitochondrial respiratory chain deficiency
Lethal neonatal cardiomyopathy hypertrophic due to cytochrome c oxidase deficiency
A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and intellectual disability. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome.
Mitochondrial complex IV deficiency, nuclear type 1
An autosomal recessive disorder of the mitochondrial respiratory chain characterized by early-onset, rapidly progressive encephalopathy, neurodegeneration, and loss of motor and cognitive skills. Affected individuals show hypotonia, failure to thrive, loss of the ability to sit or walk, poor communication, poor eye contact, oculomotor abnormalities, as well as deafness, ataxia, tremor, and brisk tendon reflexes. Brain imaging shows bilateral symmetric lesions in the basal ganglia. Lactate levels in serum and cerebrospinal fluid are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. Death in childhood may occur, often due to central respiratory failure.
Mitochondrial complex IV deficiency, nuclear type 10
An autosomal recessive mitochondrial disorder that manifests with neonatal neurological and respiratory distress. Clinical features include facial dysmorphism, hypotelorism, microphthalmia, an ogival palate, and severe metabolic acidosis. Death occurs in early infancy. Autoptic examination reveals brain hypertrophy, diffuse alteration of white matter myelination, numerous cavities in the parieto-occipital region, brainstem and cerebellum, as well as hepatomegaly, hypertrophic cardiomyopathy, renal hypoplasia, and adrenal hyperplasia. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 11
An autosomal recessive mitochondrial disorder with onset in childhood or adolescence. MC4DN11 is characterized by walking difficulties, cerebellar ataxia, dystonia, choreoathetotic movements and dysarthria. Additional features may include sensory axonal neuropathy, cerebellar atrophy, and mild speech delay. Cognitive function is normal. Serum lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 12
An autosomal recessive mitochondrial disorder with onset in early infancy. MC4DN12 features include poor overall growth, metabolic acidosis, profoundly delayed psychomotor development, seizures, hypotonia, and brain abnormalities. Death may occur in the first years of life. Serum lactate and creatine kinase levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 13
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4
An autosomal recessive, infantile disorder with a fatal course in the first weeks of life, characterized by hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, metabolic hypotonia, and mitochondrial complex IV deficiency.
Mitochondrial complex IV deficiency, nuclear type 14
An autosomal recessive mitochondrial disorder with onset in early childhood. MC4DN14 is characterized by developmental delay, cognitive impairment, motor delay, abnormal gait, sensorimotor demyelinating polyneuropathy, exercise intolerance, obesity, and short stature. Serum lactate levels are marginally increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 15
An autosomal recessive mitochondrial disorder with onset in infancy. MC4DN15 is characterized by global developmental delay, poor feeding, metabolic acidosis, short stature, microcephaly, proximal muscle weakness, and distal spasticity. Additional manifestations include scoliosis, primary pulmonary hypertension, refractory seizures, and inability to walk. Serum and CSF lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 16
An autosomal recessive mitochondrial disorder with onset in infancy and variable manifestations. MC4DN16 features include feeding difficulties, poor overall growth, short stature, microcephaly, developmental regression, severe hypotonia, and seizures. Cerebral and cerebellar atrophy, and abnormal lesions in the basal ganglia can be observed on brain imaging. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 17
An autosomal recessive mitochondrial disorder with highly variable clinical manifestations and severity. Clinical features vary from acute neurometabolic decompensation in late infancy to subtle neurological signs presenting in adolescence. Encephalopathic episodes are characterized by acute loss of developmental milestones including ability to walk or sit, loss of speech, episodes with somnolence and seizure, and pyramidal signs rapidly evolving into spastic tetraparesis. The clinical course subsequently tends to stabilize and in several subjects marked recovery of neurological milestones is observed over time. Brain imaging shows a cavitating leukodystrophy, predominantly involving the posterior cerebral white matter and the corpus callosum in the acute stage, after which the abnormalities partially improve and then stabilize. Patient tissues show variably decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 18
An autosomal recessive, muscle-specific, mitochondrial disorder with onset in infancy. MC4DN18 is characterized by hypotonia, limb and facial muscle weakness, and high arched palate. Some patients have respiratory insufficiency at birth and cardiomyopathy. Patient skeletal muscle shows decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 19
An autosomal recessive mitochondrial disorder with onset in infancy or early childhood. MC4DN19 is characterized by global developmental delay, impaired intellectual development, developmental regression, loss of acquired motor and language skills, and motor dysfunction. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 2
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1
Cytochrome c oxidase deficiency with fatal infantile cardioencephalomyopathy
An autosomal recessive, severe mitochondrial disorder characterized by hypotonia, global developmental delay, hypertrophic cardiomyopathy, lactic acidosis, gliosis, and neuronal loss in basal ganglia, brainstem and spinal cord. Serum lactate is increased, and laboratory studies show decreased mitochondrial complex IV protein and activity levels in various tissues, including heart and skeletal muscle. Most patients die in infancy of cardiorespiratory failure.
Mitochondrial complex IV deficiency, nuclear type 20
An autosomal recessive mitochondrial disorder with onset in early infancy. MC4DN20 is characterized by pulmonary arterial hypertension, poor feeding, failure to thrive, hypotonia, delayed development, increased serum lactate and metabolic acidosis. Death in infancy occurs due to cardiorespiratory failure. Patient tissues show variably decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 21
An autosomal recessive mitochondrial disorder with onset in infancy. MC4DN21 is characterized by congenital lactic acidosis, encephalopathy, global developmental delay, delayed speech, motor dysfunction, dystonia, and spasticity. Ataxia, peripheral neuropathy, and seizures may also occur. Patient tissues show variably decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 22
An autosomal recessive mitochondrial disorder characterized by hypertrophic cardiomyopathy, encephalopathy, fatal lactic acidosis, and isolated complex IV deficiency.
Mitochondrial complex IV deficiency, nuclear type 3
An autosomal recessive mitochondrial disorder characterized by cytochrome c oxidase deficiency. Clinical features include muscle weakness, hypotonia, ataxia, ptosis, metabolic acidosis, poor feeding, delayed motor development, anemia, sensorineural hearing loss, and cardiomyopathy.
Mitochondrial complex IV deficiency, nuclear type 4
An autosomal recessive mitochondrial disorder characterized by hypotonia, encephalopathy, metabolic acidosis, poor feeding, hepatomegaly, and hypertrophic cardiomyopathy in some patients. Death occurs in infancy. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 5
COX deficiency, Saguenay-Lac-Saint-Jean type
Cytochrome c oxidase deficiency, French Canadian type
Leigh syndrome, Saguenay-Lac-Saint-Jean type
An autosomal recessive, severe mitochondrial disease with multisystemic manifestations and early onset. Clinical features include delayed psychomotor development, impaired intellectual development with speech delay, mild dysmorphic facial features, hypotonia, ataxia, and seizures. Brain imaging shows bilaterally symmetrical necrotic lesions in subcortical brain regions. Mortality is high, due to episodes of severe metabolic acidosis and coma.
Mitochondrial complex IV deficiency, nuclear type 6
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2
An autosomal recessive multisystem disorder with variable manifestations. Some patients present in the neonatal period with encephalomyopathic features, whereas others present later in the first year of life with developmental regression. Clinical features include microcephaly, encephalopathy, hypertrophic cardiomyopathy, persistent lactic acidosis, respiratory distress, hypotonia and seizures. Serum lactate is increased, and laboratory studies show decreased mitochondrial complex IV protein and activity levels.
Mitochondrial complex IV deficiency, nuclear type 7
An autosomal recessive mitochondrial disorder characterized by encephalomyopathy resulting in variable clinical manifestations. Features include muscle weakness, gait disturbances, neurodegeneration, cognitive decline, metabolic acidosis, feeding difficulties, poor overall growth, cortical visual impairment, and hypertrophic cardiomyopathy. Serum lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 8
An autosomal recessive mitochondrial disorder characterized by slowly progressive cognitive dysfunction, dystonia or visual impairment that appear after an uneventful early childhood. Additional features include gait difficulties, spasticity, dysarthria, hypotonia, and variable intellectual disability. Brain imaging shows white matter abnormalities in the basal ganglia. Serum lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV.
Mitochondrial complex IV deficiency, nuclear type 9
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3
An autosomal recessive, infantile disorder with a fatal course in the first weeks of life, and characterized by hypertrophic cardiomyopathy and mitochondrial complex IV deficiency. Postmortem microscopic investigations show accumulation of lipid droplets in cardiomyocytes and mitochondrial proliferation.
Mitochondrial complex V deficiency, mitochondrial 1
Mitochondrial complex V (ATP synthase) deficiency mitochondrial type 1
A mitochondrial disorder with heterogeneous clinical manifestations including neuropathy, ataxia, hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy can present with negligible to extreme hypertrophy, minimal to extensive fibrosis and myocyte disarray, absent to severe left ventricular outflow tract obstruction, and distinct septal contours/morphologies with extremely varying clinical course.
Mitochondrial complex V deficiency, mitochondrial 2
Apical hypertrophic cardiomyopathy and neuropathy
Mitochondrial complex V (ATP synthase) deficiency mitochondrial type 2
Mitochondrial complex V deficiency, nuclear type 1
Complex 5 mitochondrial respiratory chain deficiency
Complex V mitochondrial respiratory chain deficiency
Mitochondrial complex V (ATP synthase) deficiency, ATPAF2 type
Mitochondrial complex V (ATP synthase) deficiency type 1
A mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid.
Mitochondrial complex V deficiency, nuclear type 2
Mitochondrial complex V (ATP synthase) deficiency TMEM70 type
Mitochondrial complex V (ATP synthase) deficiency type 2
Mitochondrial encephalo-cardio-myopathy due to TMEM70 deficiency
Mitochondrial neonatal encephalocardiomyopathy due to ATP synthase deficiency
Mitochondrial complex V deficiency, nuclear type 3
Mitochondrial complex V (ATP synthase) deficiency ATP5E type
Mitochondrial complex V (ATP synthase) deficiency type 3
Mitochondrial complex V deficiency, nuclear type 4
Mitochondrial complex V (ATP synthase) deficiency ATP5A1 type
Mitochondrial complex V (ATP synthase) deficiency type 4
Mitochondrial complex V deficiency, nuclear type 5
Mitochondrial complex V (ATP synthase) deficiency, ATP5F1D type
A mitochondrial disorder characterized by childhood onset of episodic metabolic decompensation featuring lactic acidosis and hyperammonemia accompanied by ketoacidosis or hypoglycemia. Chronic manifestations include developmental delay, easy fatiguability, and 3-methylglutaconic aciduria. The transmission pattern of MC5DN5 is consistent with autosomal recessive inheritance.
Mitochondrial complex V deficiency, nuclear type 6
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 6
An autosomal recessive mitochondrial disorder characterized by gross motor developmental delay manifesting in the first years of life, and subsequent episodic developmental regression. The episodes are associated with metabolic stress, including fever, illness, and general anesthesia. Patients develop gait difficulties or loss of ambulation, as well as other variable abnormalities, including abnormal movements, hemiplegia, and persistent lethargy. Brain imaging shows degenerative features in the basal ganglia and brainstem consistent with a diagnosis of Leigh syndrome.
Mitochondrial DNA depletion syndrome 1, MNGIE type
Mitochondrial neurogastrointestinal encephalomyopathy
Mitochondrial neurogastrointestinal encephalopathy syndrome TYMP-related
Myoneurogastrointestinal encephalomyopathy
Polyneuropathy ophthalmoplegia leukoencephalopathy and intestinal pseudoobstruction
A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.
Mitochondrial DNA depletion syndrome 10 (cardiomyopathic type)
An autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy.
An autosomal recessive mitochondrial disorder characterized by onset in childhood or adulthood of progressive external ophthalmoplegia, muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness. More variable features include spinal deformity, emaciation, and cardiac abnormalities. Skeletal muscle biopsies show deletion and depletion of mitochondrial DNA (mtDNA) with variable defects in respiratory chain enzyme activities.
Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type
Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type, autosomal dominant
Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) autosomal dominant
An autosomal dominant mitochondrial disorder characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies.
Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type
Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type, autosomal recessive
Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive
An autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and accumulation of abnormal mitochondria.
Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type)
An autosomal recessive disorder characterized by early infantile onset of encephalopathy, hypotonia, lactic acidosis, and severe global developmental delay. Cells derived from patient tissues show defects in mitochondrial oxidative phosphorylation and decreased mtDNA content.
Mitochondrial DNA depletion syndrome 14, cardioencephalomyopathic type
Mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type)
Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type)
An autosomal recessive mitochondrial disorder characterized by lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. Skeletal muscle biopsies show significant mtDNA depletion and abnormal mitochondria.
Mitochondrial DNA depletion syndrome 15, hepatocerebral type
Mitochondrial DNA depletion syndrome 15 (hepatocerebral type)
An autosomal recessive mitochondrial disorder characterized by severe intrauterine growth restriction, neonatal-onset hypoglycemia and liver dysfunction, mitochondrial DNA depletion in liver and skeletal muscle, and abnormal mitochondrial morphology observed in skeletal muscle. Hepatic pathology includes cirrhosis, steatosis and cholestasis. Progression to liver failure and death is rapid with no evidence of neurological impairment or other organ involvement.
Mitochondrial DNA depletion syndrome 16, hepatic type
An autosomal recessive disorder characterized by poor feeding, difficulty breathing, abdominal distention, an abnormal carnitine profile, metabolic acidosis and hepatic failure in the neonatal period. Severe mtDNA depletion is observed in liver and muscle biopsies.
Mitochondrial DNA depletion syndrome 16B, neuroophthalmic type
An autosomal recessive disorder characterized by childhood onset of progressive neuroophthalmic manifestations with optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia, and generalized chorea associated with mtDNA depletion.
An autosomal recessive mitochondrial disorder characterized by childhood onset of rapidly progressive encephalopathy, stroke-like episodes, lactic acidosis, hypocitrullinemia, multiple defects of oxidative phosphorylation, mitochondrial complex I and IV deficiency, and reduced mtDNA copy number.
An autosomal recessive mitochondrial disorder characterized by early-onset progressive weakness and atrophy of the distal limb muscles, loss of ambulation, and atrophy of the intrinsic hand muscles with clawed hands. Additional features include scoliosis, hypo- or hyperreflexia, and decreased pulmonary vital capacity. Examination of skeletal muscle shows mitochondrial respiratory chain deficiencies involving complexes I and IV, associated with mtDNA depletion.
An autosomal recessive mitochondrial disorder characterized by progressive and severe epileptic encephalopathy, hypotonia, poor spontaneous movements evolving to spastic quadriparesis and dyskinesias, and respiratory complex I deficiency and mitochondrial DNA depletion in skeletal muscle.
Mitochondrial DNA depletion myopathy TK2-related
Mitochondrial DNA depletion syndrome 2 myopathic type
Myopathic mitochondrial DNA depletion syndrome
A disorder due to mitochondrial dysfunction characterized by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later onset of a slowly progressive myopathy.
Mitochondrial DNA depletion syndrome 20, MNGIE type
Mitochondrial neurogastrointestinal encephalomyopathy syndrome, LIG3-related
An autosomal recessive mitochondrial disorder characterized by severe gut dysmotility, muscle weakness and atrophy, neurological abnormalities including epilepsy, migraine, stroke-like episodes, learning difficulties or cognitive decline, and neurogenic bladder. Brain imaging usually shows diffuse leukoencephalopathy and may show cerebellar atrophy. Disease onset can range from infancy to the teenage years.
Hepatocerebral mitochondrial DNA deletions syndrome autosomal recessive
Mitochondrial DNA depletion syndrome 3 hepatocerebral type
A disorder due to mitochondrial dysfunction characterized by onset in infancy of progressive liver failure, hypoglycemia, increased lactate in body fluids, and neurologic abnormalities including hypotonia, encephalopathy, peripheral neuropathy. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes and mtDNA depletion.
Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis
Alpers progressive infantile poliodystrophy
Mitochondrial DNA depletion syndrome 4A Alpers type
Neuronal degeneration of childhood with liver disease progressive
An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.
Mitochondrial DNA depletion syndrome 4B MNGIE type
Mitochondrial neurogastrointestinal encephalopathy syndrome POLG-related
An autosomal recessive progressive multisystem disorder due to mitochondrial dysfunction. It is clinically characterized by chronic gastrointestinal dysmotility and pseudo-obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness.
Encephalomyopathic mitochondrial DNA depletion syndrome with or without methylmalonic aciduria
Mitochondrial DNA depletion syndrome 5 encephalomyopathic with or without methylmalonic aciduria
Mitochondrial DNA depletion syndrome encephalomyopathic form with or without methylmalonic aciduria autosomal recessive SUCLA2-related
A disorder due to mitochondrial dysfunction. It is characterized by infantile onset of hypotonia, neurologic deterioration, a hyperkinetic-dystonic movement disorder, external ophthalmoplegia, deafness, variable renal tubular dysfunction, and mild methylmalonic aciduria in some patients.
Mitochondrial DNA depletion 6 hepatocerebral type
A disease due to mitochondrial dysfunction. It is characterized by infantile onset of progressive liver failure, often leading to death in the first year of life, peripheral neuropathy, corneal scarring, acral ulceration and osteomyelitis leading to autoamputation, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent infections.
Mitochondrial DNA depletion syndrome 7 hepatocerebral type
Ophthalmoplegia hypotonia ataxia hypoacusis and athetosis
Pure spinocerebellar ataxia Japanese type
Spinocerebellar ataxia infantile with sensory neuropathy
A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropathy. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. In some individuals liver dysfunction and multi-organ failure is present.
Encephalomyopathic mitochondrial depletion syndrome with renal tubulopathy
Mitochondrial DNA depletion syndrome 8A encephalomyopathic type with renal tubulopathy
Mitochondrial DNA depletion syndrome encephalomyopathic with renal tubulopathy autosomal recessive
A disorder due to mitochondrial dysfunction characterized by various combinations of neonatal hypotonia, neurological deterioration, respiratory distress, lactic acidosis, and renal tubulopathy.
Mitochondrial DNA depletion syndrome 8B MNGIE type
Mitochondrial neurogastrointestinal encephalopathy syndrome RRM2B-related
A disease due to mitochondrial dysfunction and characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy.
Mitochondrial DNA depletion syndrome 9 encephalomyopathic type with methylmalonic aciduria
A severe disorder due to mitochondrial dysfunction. It is characterized by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid.
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome
Genetically heterogeneous disorder, characterized by episodic vomiting, seizures, and recurrent cerebral insults resembling strokes and causing hemiparesis, hemianopsia, or cortical blindness.
Mitochondrial infantile bilateral striatal necrosis
Bilateral striatal necrosis is a neurological disorder resembling Leigh syndrome.
Mitochondrial myopathy with lactic acidosis
An autosomal recessive disorder characterized by progressive muscle weakness, hypotonia, seizures, poor weight gain, lactic acidosis, and elevated serum pyruvate concentration. Some patients manifest growth failure and moderate neural deafness.
Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy
An autosomal recessive neuromuscular disorder characterized by childhood onset of recurrent episodes of proximal weakness and myalgia often precipitated by exercise, infections or low temperature. Additional features are optic atrophy, axonal polyneuropathy, and reversible or partially reversible leukoencephalopathy.
Mitochondrial phosphate carrier deficiency
Neonatal hypertrophic cardiomyopathy, respiratory insufficiency, hypotonia, and lactic acidosis
An autosomal recessive disorder of oxidative phosphorylation. Patients have lactic acidosis, hypertrophic cardiomyopathy and muscular hypotonia and die within the first year of life.
Mitochondrial phosphoenolpyruvate carboxykinase deficiency
Metabolic disorder resulting from impaired gluconeogenesis. It is a rare disease with less than 10 cases reported in the literature. Clinical characteristics include hypotonia, hepatomegaly, failure to thrive, lactic acidosis and hypoglycemia. Autopsy reveals fatty infiltration of both the liver and kidneys. The disorder is transmitted as an autosomal recessive trait.
Mitochondrial pyruvate carrier deficiency
An autosomal recessive metabolic disorder characterized by severely delayed psychomotor development, mild dysmorphic features, hepatomegaly, marked metabolic acidosis, hyperlactacidemia with normal lactate/pyruvate, and encephalopathy. Some patients have epilepsy and peripheral neuropathy.
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency
A severe, autosomal recessive inborn error affecting valine metabolism. Disease features include brain lesions in the basal ganglia, neurodegeneration, delayed psychomotor development, hypotonia, spasticity, and increased lactic acid in serum and cerebral serum fluid.
Mitochondrial trifunctional protein deficiency
Trifunctional protein deficiency with myopathy and neuropathy
A disease biochemically characterized by loss of all enzyme activities of the mitochondrial trifunctional protein complex. Variable clinical manifestations include hypoglycemia, cardiomyopathy, delayed psychomotor development, sensorimotor axonopathy, generalized weakness, hepatic dysfunction, respiratory failure. Sudden infant death may occur. Most patients die from heart failure.
A form of mitral valve prolapse, a valvular heart disease characterized by abnormally elongated and thickened mitral valve leaflets, that typically show myxomatous degeneration with increased leaflet compliance. It is associated with mitral regurgitation. Myxomatous mitral valves have an abnormal layered architecture characterized by loose collagen in fibrosa, expanded spongiosa strongly positive for proteoglycans, and disrupted elastin in atrialis. In classic mitral valve prolapse, leaflets are at least 5 mm thick, whereas in the non-classic form, they are less than 5 mm thick. Severe classic mitral valve prolapse is strongly associated with arrhythmias, endocarditis, heart failure, and need for valve surgery. MVP2 inheritance is autosomal dominant.
An autosomal dominant form of mitral valve prolapse, a valvular heart disease characterized by abnormally elongated and thickened mitral valve leaflets, that typically show myxomatous degeneration with increased leaflet compliance. It is associated with mitral regurgitation. Myxomatous mitral valves have an abnormal layered architecture characterized by loose collagen in fibrosa, expanded spongiosa strongly positive for proteoglycans, and disrupted elastin in atrialis. In classic mitral valve prolapse, leaflets are at least 5 mm thick, whereas in the non-classic form, they are less than 5 mm thick. Severe classic mitral valve prolapse is strongly associated with arrhythmias, endocarditis, heart failure, and need for valve surgery.
Muscular dystrophy distal late-onset autosomal recessive
A late-onset muscular dystrophy involving the distal lower limb musculature. It is characterized by weakness that initially affects the gastrocnemius muscle during early adulthood.
A late-onset muscular dystrophy characterized by distal muscle weakness of the lower limbs, calf muscle discomfort and weakness, quadriceps atrophy. Muscle weakness and atrophy may be asymmetric.
Opticoacoustic nerve atrophy with dementia
An X-linked recessive disorder characterized by postlingual sensorineural deafness with onset in early childhood, dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness.
Molybdenum cofactor deficiency, complementation group A
Combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase
An autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients.
Molybdenum cofactor deficiency, complementation group B
An autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood.
Molybdenum cofactor deficiency, complementation group C
A form of molybdenum cofactor deficiency, an autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients.
A disorder clinically characterized by alopecia and follicular papules. Affected hairs have uniform elliptical nodes of normal thickness and intermittent constrictions, internodes at which the hair easily breaks. Usually only the scalp is involved, but in severe forms, the secondary sexual hair, eyebrows, eyelashes, and nails may also be affected.
Monocarboxylate transporter 1 deficiency
A metabolic disorder characterized by recurrent ketoacidosis, a pathologic state due to ketone formation exceeding ketone utilization. The clinical consequences of ketoacidosis are vomiting, osmotic diuresis, dehydration, and Kussmaul breathing. The condition may progress to decreased consciousness and, ultimately, death.
Monocarboxylate transporter 8 deficiency
Consists of a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels. Thyroid hormone deficiency can be caused by defects of hormone synthesis and action, but it has also been linked to a defect in cellular hormone transport. Affected patients are males with abnormal relative concentrations of three circulating iodothyronines, as well as severe neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects.
A disease characterized by median nerve mononeuropathy at the wrist. The clinical presentation ranges from a mild phenotype, consistent with carpal tunnel syndrome, to a severe median nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal polyneuropathy. The latter phenotype is similar to that of patients with hereditary neuropathy with liability to pressure palsies.
Monosomy 7 myelodysplasia and leukemia syndrome 1
A hematologic disorder characterized by bone marrow dyspoiesis and pancytopenia manifesting in early childhood, associated with monosomy 7 in the bone marrow. Disease severity ranges from transient thrombocytopenia or anemia, or normal peripheral blood counts with transient bone marrow abnormalities or transient monosomy 7, to frank myelodysplastic syndrome or acute myelogenous leukemia. M7MLS1 inheritance is autosomal dominant with incomplete penetrance and variable expressivity.
Monosomy 7 myelodysplasia and leukemia syndrome 2
A hematologic disorder manifesting in early childhood and characterized by bone marrow dyspoiesis, pancytopenia, myelodysplastic syndrome or acute myelogenous leukemia, associated with monosomy 7 in the bone marrow. Disease severity is highly variable. Inheritance is autosomal dominant with incomplete penetrance.
Morbid obesity and spermatogenic failure
An autosomal recessive morbid obesity syndrome characterized by hypertension, fatty liver disease, insulin resistance, and decreased sperm counts. Variable clinical manifestations are early coronary artery disease with myocardial infarction before 45 years of age, type II diabetes mellitus, and intellectual disability. Morbid obese individuals are defined as having a BMI greater than 40.
A severe developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases.
A form of mosaic variegated aneuploidy syndrome, a severe disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. MVA3 inheritance is autosomal recessive.
A form of mosaic variegated aneuploidy syndrome, a severe disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. MVA4 inheritance is autosomal recessive.
Mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition
A form of mosaic variegated aneuploidy syndrome, a severe disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. MVA7 is an autosomal recessive form characterized by increased susceptibility to benign and malignant neoplasms beginning in early childhood. Affected individuals show dysmorphic facies and may have early developmental delay.
A complex developmental disorder characterized by intellectual disability, delayed motor development, epilepsy, microcephaly and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. Affected patients show an easily recognizable facial appearance with deep set eyes and hypertelorism, medially divergent, broad eyebrows, prominent columella, pointed chin and uplifted, notched ear lobes. Some patients manifest Hirschsprung disease.
A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults.
Moyamoya disease 6 with or without achalasia
A form of Moyamoya disease, a progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. MYMY6 is characterized by severe cerebral angiopathy and onset of severe achalasia in infancy or early childhood.
A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs.
An autosomal dominant, mucocutaneous disease characterized by chronic mucosal lesions, in absence of recurrent infections.
An autosomal dominant genodermatosis mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo.
An autosomal recessive lysosomal storage disorder characterized by severe psychomotor retardation and ophthalmologic abnormalities, including corneal opacity, retinal degeneration and strabismus. Storage bodies of lipids and water-soluble substances are seen by electron microscopy in almost every cell type of the patients. Most patients are unable to speak or walk independently and reach a maximal developmental level of 1-2 years. All patients have constitutive achlorhydia associated with a secondary elevation of serum gastrin levels.
Fatal, autosomal recessive, lysosomal storage disorder characterized by severe clinical and radiologic features, peculiar fibroblast inclusions, and no excessive mucopolysacchariduria. Congenital dislocation of the hip, thoracic deformities, hernia, and hyperplastic gums are evident soon after birth.
Mucolipidosis type III complementation group A
Autosomal recessive disease of lysosomal enzyme targeting. Clinically MLIII is characterized by restricted joint mobility, skeletal dysplasia, and short stature. Mildly coarsened facial features and thickening of the skin have been described. Cardiac valvular disease and corneal clouding may also occur. Half of the reported patients show learning disabilities or intellectual disability.
Mucolipidosis type III complementation group C
Autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (GlcNAc-phosphotransferase) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Typical clinical findings include stiffness of the hands and shoulders, claw-hand deformity, scoliosis, short stature, coarse facies, and mild intellectual disability. Radiographically, severe dysostosis multiplex of the hip is characteristic and frequently disabling. The clinical diagnosis can be confirmed by finding elevated serum lysosomal enzyme levels and/or decreased lysosomal enzyme levels in cultured fibroblasts.
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS10 is an autosomal recessive childhood-onset disorder. Clinical features include disproportionate short-trunk short stature and skeletal, cardiac, and ophthalmologic abnormalities.
A severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe intellectual disability. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.
A form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility.
A mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.
An X-linked lysosomal storage disease characterized by intracellular accumulation of heparan sulfate and dermatan sulfate and their excretion in urine. Most children with MPS2 have a severe form with early somatic abnormalities including skeletal deformities, hepatosplenomegaly, and progressive cardiopulmonary deterioration. A prominent feature is neurological damage that presents as developmental delay and hyperactivity but progresses to intellectual disability and dementia. They die before 15 years of age, usually as a result of obstructive airway disease or cardiac failure. In contrast, those with a mild form of MPS2 may survive into adulthood, with attenuated somatic complications and often without intellectual disability.
A severe form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. MPS3A is characterized by earlier onset, rapid progression of symptoms and shorter survival.
N-acetyl-alpha-D-glucosaminidase deficiency
A form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life.
Acetyl-CoA:alpha-glucosaminide N-acetyltransferase deficiency
N-acetylglucosamine-6-sulfatase deficiency
A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life.
N-acetylgalactosamine-4-sulfatase deficiency
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS6 is an autosomal recessive form characterized by intracellular accumulation of dermatan sulfate. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities.
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS7 is an autosomal recessive form with a highly variable phenotype, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment.
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS9 is an autosomal recessive form characterized by high hyaluronan concentration in the serum. Clinical features include periarticular soft tissue masses, mild short stature and acetabular erosions, and absence of neurological or visceral involvement.
A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPSPS is an autosomal recessive form characterized by coarse facial features, dysostosis multiplex, hepatosplenomegaly, respiratory difficulties, intellectual disability, developmental delay, pyramidal signs, severe chronic anemia, renal involvement and cardiac defects. Laboratory analyses show proteinuria with glomerular foamy cells, excess secretion of urinary glycosaminoglycans, and extremely high levels of plasma heparan sulphate. Disease onset is in infancy. Most patients die in the first years of life due to cardiorespiratory failure.
FGFR3-related isolated coronal synostosis
Muenke non-syndromic coronal craniosynostosis
A condition characterized by premature closure of coronal suture of skull during development (coronal craniosynostosis), which affects the shape of the head and face. It may be uni- or bilateral. When bilateral, it is characterized by a skull with a small antero-posterior diameter (brachycephaly), often with a decrease in the depth of the orbits and hypoplasia of the maxillae. Unilateral closure of the coronal sutures leads to flattening of the orbit on the involved side (plagiocephaly). The intellect is normal. In addition to coronal craniosynostosis some affected individuals show skeletal abnormalities of hands and feet, sensorineural hearing loss, intellectual disability and respiratory insufficiency.
Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.
Pericardial constriction and growth failure
An autosomal recessive growth disorder characterized by severe growth failure of prenatal onset, constrictive pericardium and progressive cardiomyopathy, facial dysmorphism, and failure of sexual maturation. Additional clinical features include hepatomegaly, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, hypoplasia of various endocrine glands, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor.
Neurodevelopmental disorder, X-linked, with craniofacial abnormalities
An X-linked neurodevelopmental disorder with variable features including intellectual deficiency, microcephaly, microtia, hearing loss, developmental delay, dysmorphic features, language delay, congenital heart defect, and clinodactyly of the 5th finger.
Mullerian duct failure and hyperandrogenism
A disorder of sex development. Affected females manifest dysgenesis of Mullerian duct derivatives absent or rudimentary uterus and vagina, functional ovaries, primary amenorrhea, hyperandrogenism and hirsutism.
Multicentric carpotarsal osteolysis syndrome
Autosomal dominant multicentric osteolysis
Hereditary osteolysis of carpal bones with or without nephropathy
A rare skeletal disorder, usually presenting in early childhood with a clinical picture mimicking juvenile rheumatoid arthritis. Progressive destruction of the carpal and tarsal bone usually occurs and other bones may also be involved. Chronic renal failure is a frequent component of the syndrome. Intellectual disability and minor facial anomalies have been noted in some patients.
Multicentric osteolysis, nodulosis, and arthropathy
Nodulosis-arthropathy-osteolysis syndrome
An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy.
Multiminicore disease with external ophthalmoplegia
Minicore myopathy with external ophthalmoplegia
Multicore myopathy with external ophthalmoplegia
Clinically heterogeneous neuromuscular disorder. General features include neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable. Muscle biopsy shows multiple, poorly circumscribed, short areas of sarcomere disorganization and mitochondria depletion (areas termed minicores) in most muscle fibers. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present in multiminicore disease.
Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly
Hydranencephaly with renal aplasia-dysplasia
An autosomal recessive, congenital disease characterized by severe hydranencephaly with multinucleated neurons, renal aplasia or dysplasia, and hypoplastic kidneys. Hydranencephaly is an anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. MARCH results in death in utero or in the perinatal period.
Multiple congenital anomalies-hypotonia-seizures syndrome 1
Glycosylphosphatidylinositol biosynthesis defect 3
An autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age.
Multiple congenital anomalies-hypotonia-seizures syndrome 2
Epileptic encephalopathy, early infantile, 20
Glycosylphosphatidylinositol biosynthesis defect 4
An X-linked recessive developmental disorder characterized by dysmorphic features, neonatal hypotonia, myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Most affected individuals die in infancy.
Multiple congenital anomalies-hypotonia-seizures syndrome 3
Glycosylphosphatidylinositol biosynthesis defect 7
An autosomal recessive syndrome characterized by distinct facial features, intellectual disability, hypotonia and seizures, in combination with abnormal skeletal, endocrine, and ophthalmologic findings including impaired vision, as well as abnormal motility of the eyes.
Multiple congenital anomalies-hypotonia-seizures syndrome 4
Epileptic encephalopathy, early infantile, 77
Glycosylphosphatidylinositol biosynthesis defect 19
An autosomal recessive syndrome characterized by onset of refractory seizures in the first months of life. Additional clinical features include severe global developmental delay, dysmorphic facial features, and skeletal, renal and ophthalmic anomalies. At the cellular level, the disorder is caused by a defect in the synthesis of glycosylphosphatidylinositol (GPI).
Multiple congenital anomalies-neurodevelopmental syndrome, X-linked
Linkage-specific deubiquitylation deficiency-induced embryonic defects
An X-linked recessive, congenital disorder characterized by central nervous system, craniofacial, cardiac, skeletal, and genitourinary anomalies. Clinical features include poor growth, short stature, global developmental delay, impaired intellectual development, microcephaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and other variable abnormalities. Brain imaging typically shows ventriculomegaly and thin corpus callosum. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.
Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.
A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal.
A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. Multiple epiphyseal dysplasia type 4 is a recessively inherited form, characterized by early childhood-onset hip dysplasia and recurrent patella dislocation. Short stature is not frequent.
A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. Multiple epiphyseal dysplasia type 5 is relatively mild and clinically variable. It is primarily characterized by delayed and irregular ossification of the epiphyses and early-onset osteoarthritis.
Multiple epiphyseal dysplasia with myopia and conductive deafness
A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDMMD is an autosomal dominant disorder characterized by epiphyseal dysplasia associated with progressive myopia, retinal thinning, crenated cataracts, conductive deafness.
Epithelioma adenoides cysticum of Brooke
Hereditary multiple benign cystic epithelioma
Autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma.
A benign breast disease marked by lobuloalveolar growth with abnormally high proliferation of the epithelium, and characterized by the presence of more than 3 fibroadenomas in one breast. Fibroadenomas are adenomas containing fibrous tissue.
Multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects
An autosomal recessive disease characterized by dysmorphic facies, bilateral dislocations of the elbows, hips, and knees, clubfeet, and short stature, as well as cardiovascular defects.
Multiple mitochondrial dysfunctions syndrome 1
A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. Some patients show failure to thrive, pulmonary hypertension, hypotonia and irritability. Biochemical features include severe combined deficiency of the 2-oxoacid dehydrogenases, defective lipoic acid synthesis and reduction in activity of mitochondrial respiratory chain complexes.
Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia
Multiple mitochondrial dysfunctions syndrome 3
Multiple mitochondrial dysfunctions syndrome 4
A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death.
Multiple mitochondrial dysfunctions syndrome 5
An autosomal recessive, severe disorder characterized by early onset neurological deterioration, seizures, cerebral and cerebellar leukodystrophy, dysmyelination, cortical migrational abnormalities, lactic acidosis and early demise.
Multiple mitochondrial dysfunctions syndrome 6
An autosomal recessive, neurodegenerative disorder characterized by basal ganglia lesions, cerebellar atrophy, and neurologic regression in the first year of life. Common features include truncal hypotonia, lack of independent ambulation, poor speech, intellectual disability, and motor abnormalities, such as ataxia, dystonia, and spasticity.
A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia.
The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism.
Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases.
Multiple pterygium syndrome, Escobar variant
Multiple pterygium syndrome, non-lethal type
Nonlethal type multiple pterygium syndrome
Non-lethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis.
Multiple pterygium syndrome, lethal type
Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.
A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease.
Multiple self-healing squamous epithelioma
Self-healing squamous epithelioma type 1
A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars.
A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
Deafness-symphalangism syndrome of Herrmann
A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism.
A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism. SYNS4 inheritance is autosomal dominant.
A progressive neurodegenerative disorder clinically characterized by parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Pathologically, it is characterized by degeneration of striatonigral and olivopontocerebellar structures, and glial cytoplasmic inclusions that consist of abnormally phosphorylated alpha-synuclein or tau.
Multisystemic smooth muscle dysfunction syndrome
Mydriasis congenital with patent ductus arteriosus thoracic aortic aneurysm and vasculopathy
A syndrome characterized by dysfunction of smooth muscle cells throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension.
Pseudoobstruction, chronic idiopathic intestinal, with Barrett esophagus and cardiac abnormalities
Visceral neuromyopathy, familial, with pseudoobstruction, megaduodenum, Barrett esophagus, and cardiac abnormalities
An autosomal recessive disease characterized by visceral neuromyopathy, intestinal dysmotility and chronic intestinal pseudoobstruction, megaduodenum, long-segment Barrett esophagus, and a variety of cardiac valve or septal defects such as membranous ventricular septal defect, pulmonary and tricuspid valve regurgitation.
Metabolic disorder characterized by fasting hypoglycemia presenting in infancy or early childhood. The role of muscle glycogen is to provide critical energy during bursts of activity and sustained muscle work.
A condition characterized by increased muscle bulk and strength. Affected individuals are exceptionally strong.
Muscular dystrophy congenital due to integrin alpha-7 deficiency
Congenital myopathy due to integrin alpha-7 deficiency
A form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.
Muscular dystrophy congenital LMNA-related
Muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue
Muscular dystrophy, limb-girdle, type 2W
An autosomal recessive muscular dystrophy characterized by childhood-onset of muscle weakness progressing to a severe quadriparesis. Additionally, patients have biventricular cardiac dysfunction due to dilated cardiomyopathy, and macroglossia with a small tip resulting in a triangular tongue.
Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome
An autosomal recessive disorder characterized by early-onset progressive muscle weakness, sensorineural hearing loss, and primary amenorrhea due to ovarian insufficiency. Some patients become wheelchair-bound by the second decade, whereas others have a milder phenotype and maintain independent ambulation into adulthood. Most patients have respiratory insufficiency.
Muscular dystrophy, congenital, Davignon-Chauveau type
An autosomal recessive, severe congenital muscular dystrophy characterized by neonatal onset of muscle weakness predominantly involving axial muscles, life-threatening respiratory failure, skin abnormalities and joint hyperlaxity without contractures. Muscle biopsies show multi-minicores, caps and dystrophic lesions.
Muscular dystrophy, congenital, megaconial type
Muscular dystrophy, congenital, with mitochondrial structural abnormalities
An autosomal recessive, congenital muscular dystrophy characterized by early-onset muscle wasting, intellectual disability, and dilated cardiomyopathy in half of affected individuals. Some patients may die from cardiomyopathy in the first or second decade of life. Muscle biopsy shows peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center.
Muscular dystrophy, congenital, with cataracts and intellectual disability
An autosomal recessive form of muscular dystrophy with onset in early childhood and characterized by progressive muscle weakness. Almost all patients also have early-onset cataracts and intellectual disability of varying severity. Some patients have seizures.
Muscular dystrophy, congenital, with or without seizures
An autosomal recessive muscular dystrophy characterized by hypotonia and elevated serum creatine kinase levels apparent from birth. Patients have progressive muscle weakness, areflexia, and may develop seizures in early childhood or have abnormal epileptiform findings on electroencephalogram studies.
Muscular dystrophy, limb-girdle, autosomal dominant 1
Muscular dystrophy, limb-girdle, type 1D
Muscular dystrophy, limb-girdle, type 1E
An autosomal dominant myopathy characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region.
Muscular dystrophy, limb-girdle, autosomal dominant 2
Muscular dystrophy, limb-girdle, type 1F
An autosomal dominant myopathy characterized by proximal muscle weakness primarily affecting the lower limbs, but also affecting the upper limbs in most patients. Affected individuals also have distal muscle weakness of the hands and lower leg muscles. The disease has generally a benign clinical course but some individuals with childhood or juvenile onset manifest severe widespread myopathy, leading to wheelchair dependency and respiratory insufficiency. Muscle biopsy shows dystrophic changes with abnormal nuclei, rimmed vacuoles, and filamentous inclusions.
Muscular dystrophy, limb-girdle, autosomal dominant 3
Muscular dystrophy, limb-girdle, type 1G
An autosomal dominant degenerative myopathy characterized by slowly progressive wasting and weakness of the proximal muscles of arms and legs around the pelvic or shoulder girdles, elevated creatine kinase levels and dystrophic features on muscle biopsy. LGMDD3 is characterized by a mild late-onset and is associated with progressive fingers and toes flexion limitation. Affected individuals may also develop cataracts before age 50.
Muscular dystrophy, limb-girdle, autosomal dominant 4
Muscular dystrophy, limb-girdle, type 1I
A form of autosomal dominant limb-girdle muscular dystrophy, a myopathy characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. LGMDD4 is characterized by onset of proximal muscle weakness in young adulthood, gait difficulties, increased serum creatine kinase, myalgia, and back pain. Some patients may have upper limb involvement. Disease severity and expressivity are highly variable.
Muscular dystrophy, limb-girdle, autosomal recessive 1
Muscular dystrophy, limb-girdle, type 2A
An autosomal recessive degenerative myopathy characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. The symptoms usually begin during the first two decades of life, and the disease gradually worsens, often resulting in loss of walking ability 10 or 20 years after onset.
Muscular dystrophy, limb-girdle, autosomal recessive 10
Muscular dystrophy, limb-girdle, type 2J
An autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle muscles. Severe disability is observed within 20 years of onset.
Muscular dystrophy, limb-girdle, autosomal recessive 12
Muscular dystrophy, limb-girdle, type 2L
An autosomal recessive degenerative myopathy characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy.
Muscular dystrophy, limb-girdle, autosomal recessive 17
Muscular dystrophy, limb-girdle, type 2Q
A form of limb-girdle muscular dystrophy characterized by early childhood onset of proximal muscle weakness. Limb-girdle muscular dystrophies are characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy.
Muscular dystrophy, limb-girdle, autosomal recessive 18
Muscular dystrophy, limb-girdle, type 2S
A form of limb-girdle muscular dystrophy characterized by proximal muscle weakness with childhood onset, resulting in gait abnormalities and scapular winging. Serum creatine kinase is increased. A subset of patients may show a hyperkinetic movement disorder with chorea, ataxia, or dystonia and global developmental delay.
Muscular dystrophy, limb-girdle, autosomal recessive 2
Muscular dystrophy, limb-girdle, type 2B
An autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs.
Muscular dystrophy, limb-girdle, autosomal recessive 21
Muscular dystrophy, limb-girdle, type 2Z
A form of autosomal recessive limb-girdle muscular dystrophy, a degenerative myopathy characterized by slowly progressive wasting and weakness of the proximal muscles of arms and legs around the pelvic or shoulder girdles, elevated creatine kinase levels and dystrophic features on muscle biopsy. LGMDR21 is characterized by young-adult onset.
Muscular dystrophy, limb-girdle, autosomal recessive 23
A form of autosomal recessive limb-girdle muscular dystrophy, a myopathy characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. LGMDR23 is characterized by slowly progressive proximal muscle weakness primarily affecting the lower limbs, increased serum creatine kinase, dystrophic features, gait difficulties, and white matter abnormalities on brain imaging. Age at onset generally ranges from childhood to mid-adulthood. Some patients may have additional neurologic features, including executive deficits, seizures, and peripheral neuropathy.
Muscular dystrophy, limb-girdle, autosomal recessive 25
Cardiac arrhythmia with increased serum creatine kinase
Muscular dystrophy, limb-girdle, type 2X
An autosomal recessive muscular disorder characterized by slowly progressive onset of proximal lower limb weakness in adulthood, syncopal episodes, and markedly increased serum creatine kinase, which can increase further after strenuous exercise.
Muscular dystrophy, limb-girdle, autosomal recessive 26
An autosomal recessive muscular disorder characterized by adult onset of weakness and atrophy of proximal limb muscles, elevated serum creatine kinase levels, and dystrophic findings on muscle biopsy. There is no cardiac or respiratory involvement.
Muscular dystrophy, limb-girdle, autosomal recessive 27
An autosomal recessive muscular disorder characterized by progressive muscle weakness most prominent in the proximal lower limb and axial muscles, and resulting in walking difficulty or loss of ambulation. Additional more variable features include neck muscle weakness, scoliosis, and joint contractures. Some affected individuals manifest impaired intellectual development or speech delay, cardiomyopathy, and cardiac arrhythmia. Muscle biopsy shows non-specific dystrophic changes.
Muscular dystrophy, limb-girdle, autosomal recessive 3
Duchenne-like muscular dystrophy autosomal recessive type 2
Muscular dystrophy, limb-girdle, type 2D
Severe childhood autosomal recessive muscular dystrophy
An autosomal recessive degenerative myopathy characterized by progressive muscle wasting from early childhood with loss of independent ambulation by teenage years. Muscle biopsy shows necrosis, decreased immunostaining for alpha sarcoglycan, and adhalin deficiency.
Muscular dystrophy, limb-girdle, autosomal recessive 4
Muscular dystrophy, limb-girdle, type 2E
An autosomal recessive degenerative myopathy characterized by pelvic and shoulder muscle wasting, onset usually in childhood and variable progression rate.
Muscular dystrophy, limb-girdle, autosomal recessive 5
Duchenne-like muscular dystrophy autosomal recessive type 1
Muscular dystrophy, limb-girdle, type 2C
Severe childhood autosomal recessive muscular dystrophy North African type
An autosomal recessive degenerative myopathy characterized by rapidly progressive muscle wasting from early childhood with loss of independent ambulation around age 12 years, dystrophic pattern on muscle biopsy, absence of gamma-sarcoglycan and normal dystrophin immunostaining.
Muscular dystrophy, limb-girdle, autosomal recessive 6
Muscular dystrophy, limb-girdle, type 2F
An autosomal recessive degenerative myopathy initially affecting the proximal limb girdle musculature. Muscle from patients shows a complete loss of delta-sarcoglycan as well as of the others components of the sarcoglycan complex.
Muscular dystrophy, limb-girdle, autosomal recessive 7
Muscular dystrophy, limb-girdle, type 2G
An autosomal recessive degenerative myopathy characterized by proximal and distal muscle weakness and atrophy in the limbs, dystrophic changes on muscle biopsy, and absence of telethonin. Cardiac muscle is involved in a subset of patients.
Muscular dystrophy, limb-girdle, autosomal recessive 8
Muscular dystrophy, limb-girdle, type 2H
An autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A1
Cerebroocular dysplasia-muscular dystrophy syndrome
Muscular dystrophy due to defective glycosylation of dystroglycan 1A
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1
An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease.
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A10
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A11
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11
Walker-Warburg syndrome or muscle-eye-brain disease B3GALNT2-related
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A12
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12
Walker-Warburg syndrome or muscle-eye-brain disease POMK-related
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A13
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13
Walker-Warburg syndrome or muscle-eye-brain disease B3GNT1-related
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A14
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14
Walker-Warburg syndrome or muscle-eye-brain disease GMPPB-related
An autosomal recessive disorder characterized by congenital muscular dystrophy associated with brain anomalies, eye malformations, and profound intellectual disability. The disorder includes a severe form designated as Walker-Warburg syndrome and a less severe phenotype known as muscle-eye-brain disease. MDDGA14 features include increased muscle tone, microcephaly, cleft palate, feeding difficulties, severe muscle weakness, sensorineural hearing loss, cerebellar hypoplasia, ataxia, and retinal dysfunction.
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A2
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3
Muscle-eye-brain disease POMGNT1-related
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3
An autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, cobblestone lissencephaly, and cerebellar and pontine hypoplasia. Patients present severe congenital myopia, congenital glaucoma, pallor of the optic disks, retinal hypoplasia, intellectual disability, hydrocephalus, abnormal electroencephalograms, generalized muscle weakness and myoclonic jerks. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease.
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A4
Congenital muscular dystrophy Fukuyama type
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A5
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A7
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A8
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A9
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9
Walker-Warburg syndrome or muscle-eye brain disease, DAG1-related
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B1
Muscular dystrophy congenital POMT1-related
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 1
An autosomal recessive disorder characterized by congenital muscular dystrophy associated with intellectual disability and mild structural brain abnormalities.
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B14
Congenital muscular dystrophy GMPPB-related
A congenital muscular dystrophy characterized by severe muscle weakness apparent in infancy and intellectual disability. Some patients may have additional features, such as microcephaly, cardiac dysfunction, seizures, or cerebellar hypoplasia.
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B15
Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15
An autosomal recessive, congenital muscular disorder characterized by hyperCKemia, myopathic features observed on muscle biopsy, developmental delay, mildly impaired intellectual development with learning difficulties, epilepsy, and mild white matter abnormalities.
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B2
Muscular dystrophy congenital POMT2-related
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B3
Muscular dystrophy congenital POMGNT1-related
An autosomal recessive disorder characterized by congenital muscular dystrophy associated with intellectual disability and mild structural brain abnormalities. Clinical features include intellectual disability, white matter changes, cerebellar cysts, pontine hypoplasia, myopia, optic atrophy, decreased alpha-dystroglycan on muscle biopsy and increased serum creatine kinase.
Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B6
A congenital muscular dystrophy associated with profound intellectual disability, white matter changes and structural brain abnormalities. Skeletal muscle biopsies show reduced immunolabeling of alpha-dystroglycan.
Muscular dystrophy-dystroglycanopathy congenital with or without impaired intellectual development B5
A congenital muscular dystrophy characterized by a severe phenotype with inability to walk, muscle hypertrophy, marked elevation of serum creatine kinase, secondary deficiency of laminin alpha2, and a marked reduction in alpha-dystroglycan expression. Only a subset of affected individuals have brain involvements.
Muscular dystrophy-dystroglycanopathy congenital without impaired intellectual development B4
Muscular dystrophy congenital FKTN-related
An autosomal recessive disorder characterized by congenital muscular dystrophy and evidence of dystroglycanopathy. Features included increased serum creatine kinase, generalized weakness, mild white matter changes on brain MRI, and absence of intellectual disability.
Muscular dystrophy-dystroglycanopathy limb-girdle C1
Muscular dystrophy, limb-girdle, autosomal recessive 11
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1
An autosomal recessive degenerative myopathy associated with mild intellectual disability without any obvious structural brain abnormality. An abnormal alpha-dystroglycan pattern in observed in the muscle.
Muscular dystrophy-dystroglycanopathy limb-girdle C12
Muscular dystrophy-dystroglycanopathy, limb-girdle, POMK-related
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 12
An autosomal recessive limb-girdle congenital muscular dystrophy, characterized by muscle weakness and delayed motor development in association with cognitive impairment.
Muscular dystrophy-dystroglycanopathy limb-girdle C14
Muscular dystrophy, limb-girdle, autosomal recessive 19
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14
Muscular dystrophy-dystroglycanopathy limb-girdle GMPPB-related
An autosomal recessive form of muscular dystrophy characterized by mild proximal muscle weakness with onset in early childhood. Some patients may have additional features, such as mild intellectual disability or seizures.
Muscular dystrophy-dystroglycanopathy limb-girdle C15
Congenital disorder of glycosylation type Io
Muscular dystrophy-dystroglycanopathy, limb-girdle, DPM3-related
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15
An autosomal recessive muscular dystrophy associated with a disorder of glycosylation resulting in under-glycosylated serum glycoproteins. MDDGC15 patients have muscle weakness, increased serum creatine kinase, dystrophic changes on muscle biopsy, and reduced O-mannosylation of alpha-dystroglycan.
Muscular dystrophy-dystroglycanopathy limb-girdle C2
Muscular dystrophy, limb-girdle, autosomal recessive 14
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2
Muscular dystrophy-dystroglycanopathy limb-girdle POMT2-related
An autosomal recessive muscular dystrophy with onset after ambulation is achieved. MDDGC2 is characterized by increased serum creatine kinase and mild muscle weakness. Muscle biopsy shows dystrophic changes, inflammatory changes, and severely decreased alpha-dystroglycan. Cognition is normal.
Muscular dystrophy-dystroglycanopathy limb-girdle C3
Muscular dystrophy, limb-girdle, autosomal recessive 15
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3
Muscular dystrophy-dystroglycanopathy limb-girdle POMGNT1-related
A rare form of limb-girdle muscular dystrophy with normal cognition. Muscle biopsy shows dystrophic changes with variable staining for glycosylated alpha-dystroglycan.
Muscular dystrophy-dystroglycanopathy limb-girdle C4
Muscular dystrophy, limb-girdle, autosomal recessive 13
Muscular dystrophy due to defective glycosylation of dystroglycan 4C
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4
An autosomal recessive degenerative myopathy characterized by progressive weakness of the pelvic and shoulder girdle muscles, and elevated serum creatine kinase. MDDGC4 has no brain involvement and a remarkable clinical response to corticosteroids.
Muscular dystrophy-dystroglycanopathy limb-girdle C5
Muscular dystrophy, limb-girdle, autosomal recessive 9
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5
Muscular dystrophy-dystroglycanopathy limb-girdle FRKP-related
An autosomal recessive degenerative myopathy with age of onset ranging from childhood to adult life, and variable severity. Clinical features include proximal muscle weakness, waddling gait, calf hypertrophy, cardiomyopathy and respiratory insufficiency. A reduction of alpha-dystroglycan and laminin alpha-2 expression can be observed on skeletal muscle biopsy from MDDGC5 patients.
Muscular dystrophy-dystroglycanopathy limb-girdle C7
Muscular dystrophy, limb-girdle, autosomal recessive 20
Muscular dystrophy, limb-girdle, type 2U
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 7
A form of muscular dystrophy resulting from defective glycosylation of alpha-dystroglycan, and characterized by a limb-girdle phenotype with muscular weakness apparent after ambulation is achieved. MDDGC7 individuals do not show epilepsy, intellectual disability, structural eye/brain abnormalities, or white matter changes.
Muscular dystrophy-dystroglycanopathy limb-girdle C8
Muscular dystrophy, limb-girdle, autosomal recessive 24
Muscular dystrophy-dystroglycanopathy, limb-girdle, POMGNT2-related
An autosomal recessive muscular disease with onset in childhood, characterized by limb-girdle muscular dystrophy and intellectual disability without brain malformation. Disease severity is highly variable and some patients may be clinically asymptomatic.
Muscular dystrophy-dystroglycanopathy limb-girdle C9
Muscular dystrophy, limb-girdle, autosomal recessive 16
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9
Muscular dystrophy-dystroglycanopathy limb-girdle DAG1-related
An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with intellectual disability without structural brain anomalies.
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS10 is an autosomal recessive, post-synaptic form characterized by a typical 'limb girdle' pattern of muscle weakness with small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function.
Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS11 is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.
Limb-girdle myasthenia with tubular aggregates
Myasthenia, congenital, with tubular aggregates 1
Myasthenic syndrome, congenital, with tubular aggregates, 1
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS12 is characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.
Myasthenic syndrome, congenital, with tubular aggregates, 2
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS13 is characterized by muscle weakness mostly affecting proximal limb muscles, minimal involvement of facial, ocular and bulbar muscles, and tubular aggregates present on muscle biopsy. Symptoms include difficulty walking and frequent falls. Younger patients show hypotonia and poor head control. Neurophysiological features indicate a disorder of neuromuscular transmission on electromyography.
Myasthenic syndrome, congenital, 14, with tubular aggregates
Myasthenic syndrome, congenital, with tubular aggregates, 3
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS14 is an autosomal recessive form characterized by onset of limb-girdle muscle weakness in early childhood. The disorder is slowly progressive, and some patients may become wheelchair-bound.
Myasthenic syndrome, congenital, 15, without tubular aggregates
Myasthenic syndrome, congenital, without tubular aggregates
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness.
Congenital myasthenic syndrome due to mutation in SCN4A
Congenital myasthenic syndrome SCN4A-related
Myasthenic syndrome, congenital, acetazolamide-responsive
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS16 is characterized by fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation.
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort.
Myasthenic syndrome, congenital, 18 with intellectual disability and ataxia
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS18 is an autosomal dominant presynaptic disorder clinically characterized by early-onset muscle weakness and easy fatigability associated with delayed psychomotor development and ataxia.
Myasthenic syndrome, congenital, 1A, slow-channel
Congenital myasthenic syndrome post-synaptic slow-channel
Myasthenic syndrome, congenital, slow-channel
A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS1A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
Myasthenic syndrome, congenital, 1B, fast-channel
Myasthenic syndrome, congenital, fast-channel
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS1B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Myasthenic syndrome, congenital, 20, presynaptic
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS20 is an autosomal recessive, pre-synaptic form characterized by severe hypotonia and episodic apnea soon after birth, generalized limb fatigability and weakness, delayed walking, ptosis, poor sucking and swallowing.
Myasthenic syndrome, congenital, 21, presynaptic
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS21 is an autosomal recessive, pre-synaptic form characterized by ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water. Learning difficulties and left ventricular dysfunction may be present in some patients.
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS22 is an autosomal recessive form characterized by neonatal hypotonia.
Myasthenic syndrome, congenital, 23, presynaptic
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS23 inheritance is autosomal recessive.
Myasthenic syndrome, congenital, 24, presynaptic
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS24 inheritance is autosomal recessive.
Myasthenic syndrome, congenital, 25, presynaptic
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS25 is an autosomal recessive form characterized by hypotonia and generalized muscle weakness apparent from birth. Affected individuals have feeding difficulties and delayed motor development, usually never achieving independent ambulation. Additional variable features include eye movement abnormalities, joint contractures, and rigid spine.
Myasthenic syndrome, congenital, 2A, slow-channel
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. CMS2C is clinically characterized by early-onset muscle weakness with variable severity.
Myasthenic syndrome, congenital, 3A, slow-channel
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
Myasthenic syndrome, congenital, 3B, fast-channel
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.
Myasthenic syndrome, congenital, 4A, slow-channel
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.
Myasthenic syndrome, congenital, 4B, fast-channel
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency
Congenital myasthenic syndrome post-synaptic associated with acetylcholine receptor deficiency
Congenital myasthenic syndrome with facial dysmorphism associated with acetylcholine receptor deficiency
Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.
Endplate acetylcholinesterase deficiency
End-plate acetylcholinesterase deficiency
Myasthenic syndrome, congenital, Engel type
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS5 inheritance is autosomal recessive.
Myasthenic syndrome, congenital, 6, presynaptic
Congenital myasthenic syndrome pre-synaptic associated with episodic apnea
Myasthenic syndrome, congenital, associated with episodic apnea
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS6 affected individuals have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement. CMS6 inheritance is autosomal recessive.
Myasthenic syndrome, congenital, 7A, presynaptic, and distal motor neuropathy, autosomal dominant
Myasthenic syndrome, presynaptic, congenital, with or without motor neuropathy
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS7A is an autosomal dominant, presynaptic disorder resembling Lambert-Eaton myasthenic syndrome. Affected individuals have a variable degree of proximal and distal limb weakness, muscle fatigue that improves with rest, mild gait difficulties, and reduced or absent deep tendon reflexes.
Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive
An autosomal recessive form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS7B is characterized by defects at the pre-synaptic neuromuscular junction and severe generalized muscle weakness apparent from birth. Decreased fetal movements may be apparent in utero. Affected infants have generalized hypotonia, head lag, and facial muscle weakness with ptosis. Some patients may have respiratory involvement.
Congenital myasthenic syndrome due to agrin deficiency
Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects
Myasthenic syndrome, congenital, with pre- and postsynaptic defects
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS8 is an autosomal recessive disease characterized by prominent defects of both the pre- and postsynaptic regions. Affected individuals have onset of muscle weakness in early childhood; the severity of the weakness and muscles affected is variable.
Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS9 is a disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.
A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML).
A disorder characterized by replacement of the bone marrow by fibrous tissue, occurring in association with a myeloproliferative disorder. Clinical manifestations may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension.
Agnogenic myeloid metaplasia with myelofibrosis
A chronic myeloproliferative disorder characterized by replacement of the bone marrow by fibrous tissue, extramedullary hematopoiesis, anemia, leukoerythroblastosis and hepatosplenomegaly.
A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis.
Myeloproliferative disorder chronic with eosinophilia
A hematologic disorder characterized by malignant eosinophils proliferation.
Myeloproliferative/lymphoproliferative neoplasms, familial
Myeloproliferative/lymphoproliferative neoplasms, familial (multiple types)
A familial cancer predisposition syndrome with incomplete penetrance, characterized by increased susceptibility to myeloid neoplasms and rarely to lymphoid malignancies. MPLPF inheritance is autosomal dominant.
Growth-mental deficiency syndrome of Myhre
A syndrome characterized by pre- and postnatal growth deficiency, intellectual disability, generalized muscle hypertrophy and striking muscular build, decreased joint mobility, cryptorchidism, and unusual facies. Dysmorphic facial features include microcephaly, midface hypoplasia, prognathism, and blepharophimosis. Typical skeletal anomalies are short stature, square body shape, broad ribs, iliac hypoplasia, brachydactyly, flattened vertebrae, and thickened calvaria. Other features, such as congenital heart disease, may also occur.
A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia.
A form of epilepsy characterized by myoclonic-atonic and absence seizures, appearing in early childhood. Patients have delayed development before the onset of seizures and show varying degrees of intellectual disability following seizure onset.
An autosomal dominant neurologic condition characterized by adult onset of cortical myoclonus manifest as involuntary jerks or movements affecting the face and limbs. Affected individuals can also experience falls without seizure activity or loss of consciousness.
An autosomal dominant neurologic disorder characterized by upper limb isolated myoclonus without seizures or cognitive impairment. MYOCL2 is a non-progressive disease with onset in the first decade of life.
An autosomal dominant neurologic disorder characterized by severe, infantile-onset myoclonic seizures, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest. Brain imaging shows a progressive leukoencephalopathy. Some patients may die in infancy.
Myoectodermal gonadal dysgenesis syndrome
Brosnan-Kennerknecht-Guran-Koc syndrome BKGK
Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy
An autosomal recessive disorder characterized by 46,XY complete gonadal dysgenesis and extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay.
A rare mesenchymal disorder characterized by the development of benign tumors in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about half of the patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life. Visceral lesions are associated with high morbidity and mortality.
Myoglobinuria, acute recurrent, autosomal recessive
Familial paroxysmal paralytic myoglobinuria
Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness and followed by excretion of myoglobin in the urine. Renal failure may occasionally occur.
A condition characterized by spontaneous involuntary contraction of muscle fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Isolated spontaneous muscle twitches occur in many persons and have no grave significance.
Myopathy due to myoadenylate deaminase deficiency
Adenosine monophosphate deaminase deficiency muscle type
A metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue.
Myopathy with exercise intolerance Swedish type
Hereditary myopathy with lactic acidosis
Myoglobinuria due to abnormal glycolysis
Myopathy with deficiency of succinate dehydrogenase and aconitase
Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism.
An autosomal recessive disorder characterized by early-onset proximal muscle weakness with a static course and moderately to grossly elevated serum creatine kinase levels accompanied by learning difficulties. Most patients develop subtle extrapyramidal motor signs that progress to a debilitating disorder of involuntary movement with variable features, including chorea, tremor, dystonic posturing and orofacial dyskinesia. Additional variable features include ataxia, microcephaly, ophthalmoplegia, ptosis, optic atrophy and axonal peripheral neuropathy.
Myopathy with lactic acidosis and sideroblastic anemia 1
Mitochondrial myopathy and sideroblastic anemia
A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest progressive muscle weakness, exercise intolerance, lactic acidosis, sideroblastic anemia and delayed growth.
Myopathy with lactic acidosis and sideroblastic anemia 2
A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest sideroblastic anemia, progressive lethargy, muscle weakness, and exercise intolerance associated with persistent lactic acidemia.
Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis
An autosomal recessive muscular disorder characterized by mild muscle weakness, early fatigue after mild to moderate physical exertion, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and elevated serum creatine kinase levels. Rarely, affected individuals may demonstrate cardiac involvement, including left ventricular dysfunction or rhythm abnormalities.
Myopathy, actin, congenital, with excess of thin myofilaments
A congenital muscular disorder characterized at histological level by areas of sarcoplasm devoid of normal myofibrils and mitochondria, and replaced with dense masses of thin filaments. Central cores, rods, ragged red fibers, and necrosis are absent.
Myopathy, autosomal recessive, with rigid spine and distal joint contractures
Muscular dystrophy, limb-girdle, type 2Y
An autosomal recessive degenerative myopathy characterized by muscle weakness initially involving the proximal lower limbs, followed by distal upper and lower limb muscle weakness and atrophy. Other features include joint contractures, rigid spine, and restricted pulmonary function. Cardiac involvement has been observed in some patients. Disease onset is in the first or second decades of life.
Centronuclear myopathy autosomal dominant
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Centronuclear myopathy autosomal recessive
A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM5 features include severe neonatal hypotonia with respiratory insufficiency, difficulty feeding, and delayed motor development. Some patients die in infancy, and some develop dilated cardiomyopathy.
Myopathy, centronuclear, 6, with fiber-type disproportion
A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal recessive, slowly progressive form with onset in infancy or early childhood.
Myopathy, congenital proximal, with minicore lesions
An autosomal recessive, slowly progressive muscular disorder characterized by primarily proximal muscle weakness, neonatal hypotonia leading to delayed motor development, mildly delayed walking in childhood, and difficulty running or climbing. Cardiac function is unaffected, but most patients have obstructive sleep apnea. Muscle biopsy shows type 1 fiber predominance with disorganized Z-lines and minicores that disrupt the myofibrillar striation pattern.
Congenital myopathy with cleft palate and malignant hyperthermia
An autosomal recessive disease characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia provoked by anesthesia.
A lethal, autosomal recessive, congenital myopathy characterized by fetal akinesia, neonatal hypotonia, severe muscle weakness, loss of beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma and disruption of sarcomeres with disorganization of the Z band.
An autosomal recessive skeletal muscle disorder characterized clinically by severe hypotonia apparent at birth, motor delay, and walking difficulties. The course of the disease is non-progressive, and affected individuals achieve independent ambulation and tend to show improvement of muscle weakness throughout childhood and early adulthood.
Myopathy, congenital, progressive, with scoliosis
An autosomal recessive muscular disorder characterized by infantile onset of progressive muscular atrophy, hypotonia, ptosis, scoliosis and dysmorphic facial features. Disease severity is variable, ranging from mild to severe.
Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies
Myopathy, congenital, due to MYOD1 deficiency
An autosomal recessive muscular disorder characterized by hypotonia and respiratory insufficiency apparent soon after birth, high diaphragmatic dome on imaging, poor overall growth, pectus excavatum, dysmorphic facies, and renal anomalies in some affected individuals. Additional variable features include delayed motor development, mildly decreased endurance, distal arthrogryposis, and lung hypoplasia resulting in early death.
Myopathy, congenital, with fast-twitch type II fiber atrophy
Myopathy, congenital, with fast-twitch (type II) fiber atrophy
An autosomal recessive congenital myopathy characterized by decreased fetal movements, severe muscle weakness and respiratory failure. Additional features include delayed motor development, areflexia, facial weakness, normal eye movements, head lag, and mild contractures. Skeletal muscle biopsy shows variation in fiber size with atrophy of the fast-twitch type II fibers.
Myopathy, congenital, with fiber-type disproportion
Congenital fiber-type disproportion myopathy
A genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions.
Myopathy, congenital, with neonatal respiratory insufficiency
An autosomal dominant myopathy characterized by neonatal onset of hypotonia, muscle weakness, and respiratory muscle involvement resulting in severe respiratory insufficiency. The disorder improves over time, although forced vital capacity remains decreased. Other features include facial weakness, often with ptosis or external ophthalmoplegia, jaw or distal joint contractures, scoliosis, and osteopenia.
Myopathy, congenital, with respiratory insufficiency and bone fractures
An autosomal recessive muscular disorder characterized by severe hypotonia apparent at birth, poor feeding, ulnar deviation of the hands, laterally deviated feet, fractures of the long bones, respiratory insufficiency due to muscle weakness, and death in infancy.
Myopathy, congenital, with structured cores and Z-line abnormalities
An autosomal dominant muscular disorder characterized by progressive early-onset muscle weakness, gait difficulties, loss of ambulation, and respiratory insufficiency. Morphological and ultrastructural analyses of muscle biopsies reveal type 1 fiber predominance, multiple structured cores forming a circular arrangement beneath the sarcolemma, and jagged Z-lines.
An autosomal dominant muscular disorder characterized by muscle weakness, hypotonia associated with high-frequency postural tremor of the limbs, mildly delayed walking, and steppage gait. Additional features include skeletal deformities such as scoliosis, thoracic asymmetry and spinal rigidity. Some patients show mild facial dysmorphic features. Cognitive functions are normal.
Myopathy distal early-onset autosomal dominant
A muscular disorder characterized by early-onset selective weakness of the great toe and ankle dorsiflexors, followed by weakness of the finger extensors. Mild proximal weakness occasionally develops years later after the onset of the disease.
A slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation.
A form of distal myopathy, a group of muscular disorders characterized by progressive muscular weakness and muscle atrophy beginning in the hands, the legs or the feet. MPD5 is an autosomal recessive form, predominantly affecting the lower limbs.
Myopathy, distal, 6, adult onset, autosomal dominant
An autosomal dominant muscular disorder characterized by adult onset of asymmetric distal muscle weakness, primarily affecting the lower limbs and resulting in gait difficulties. Some patients develop involvement of proximal and upper limb muscles.
Myopathy, distal, 7, adult-onset, X-linked
An X-linked recessive, slowly progressive muscular disorder characterized by adult onset of distal muscle weakness predominantly, affecting the lower limbs. Some patients also have proximal muscle weakness. Histopathological and electron microscopic analysis of patient muscle biopsies reveals myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics.
A disorder characterized by progressive muscular atrophy and muscle weakness beginning in the hands, the legs, or the feet. Muscle atrophy may be restricted to the small muscles of the hands and feet.
An autosomal dominant myopathy with adult onset, characterized by muscle weakness of the distal upper and lower limbs, walking difficulties, and proximal weakness of the shoulder girdle muscles. Muscle biopsy shows rimmed vacuoles.
Myopathy, early-onset, areflexia, respiratory distress, and dysphagia
An autosomal recessive congenital myopathy characterized by onset at birth, or early in infancy, of respiratory distress caused by diaphragmatic weakness. Additional features are dysphagia resulting in poor feeding, failure to thrive, poor head control, facial weakness, cleft palate, contractures and scoliosis. Affected individuals become ventilator-dependent, and most require feeding by gastrostomy. The disorder results in severe muscle weakness and most patients never achieve walking. Death from respiratory failure in childhood occurs in about half of patients. Muscle biopsies from affected individuals show myopathic changes, replacement of myofibers with fatty tissue, small and incompletely fused muscle fibers, and variation in fiber size. Short regions of sarcomeric disorganization with few or no mitochondria (minicores) have been observed in some cases.
Myopathy, epilepsy, and progressive cerebral atrophy
An autosomal recessive disorder characterized by severe, early lethal neurodegeneration, myasthenic and myopathic features, progressive cerebral atrophy with myelination defects, and intractable epilepsy.
Myopathy, isolated mitochondrial, autosomal dominant
A mitochondrial myopathy presenting with severe exercise intolerance, progressive proximal weakness, and lactic acidemia. The disorder is slowly progressive, with later involvement of facial muscles, muscles of the upper limbs, and distal muscles.
Myopathy, lactic acidosis, and sideroblastic anemia 3
A rare mitochondrial disorder characterized by sideroblastic anemia, muscle weakness, and exercise intolerance associated with persistent lactic acidemia. Additional MLASA3 features are failure to thrive, hearing loss, epilepsy, stroke-like episodes, and severe developmental delay.
Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay
Combined mitochondrial complex deficiency
Myopathy with cataract and combined respiratory chain deficiency
A disease characterized by progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay.
A neuromuscular disorder characterized by muscle weakness and atrophy, ataxia, poor growth, delayed motor development, dysdiadochokinesia, dysmetria and additional neurologic features. Some patients show skeletal and endocrine anomalies, as well as behavioral psychiatric manifestations. MMYAT transmission pattern is consistent with autosomal dominant inheritance in some families, and autosomal recessive inheritance in others.
Arrhythmogenic right ventricular cardiomyopathy 7
Autosomal dominant inclusion body myopathy 1
Desmin-related myopathy with arrhythmogenic right ventricular cardiomyopathy
Dilated cardiomyopathy 1F and limb-girdle muscular dystrophy type 1D
Dilated cardiomyopathy with conduction defect and muscular dystrophy
Familial arrhythmogenic right ventricular dysplasia 7
Muscular dystrophy, limb-girdle, type 2R
Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM1 is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM10 is an autosomal recessive disorder characterized by muscle pain, cramping, exercise fatigue, and progressive muscle rigidity.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM11 is an autosomal recessive form characterized by onset of slowly progressive proximal muscle weakness in the first decade of life. More variable features may include decreased respiratory forced vital capacity, variable cardiac features, and calf hypertrophy. Skeletal muscle biopsy shows myopathic changes with variation in fiber size, type 1 fiber predominance, centralized nuclei, eccentrically placed core-like lesions, and distortion of the myofibrillary pattern with Z-line streaming and abnormal myofibrillar aggregates or inclusions.
Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM12 is an autosomal recessive, severe form characterized by progressive myopathy with onset shortly after birth, tremor or clonus at birth, and cardiomyopathy usually leading to death by 6 months of age. Skeletal and cardiac muscle tissues show fiber-type disproportion with small type I and normal sized type II fibers, and myofibrillar disorganization.
Myofibrillar myopathy alpha-B crystallin-related
Myofibrillar myopathy with or without cataract and/or cardiomyopathy
Myopathy cardioskeletal desmin-related with cataract
Myopathy desmin-related associated with mutation in the CRYAB gene
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM2 is characterized by weakness of the proximal and distal limb muscles, weakness of the neck, velopharynx and trunk muscles, hypertrophic cardiomyopathy, and cataract in a subset of patients.
Muscular dystrophy, limb-girdle, type 1A
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM3 is characterized by progressive skeletal muscle weakness greater distally than proximally, tight heel cords, hyporeflexia, cardiomyopathy and peripheral neuropathy in some patients. Affected muscle exhibits disorganization and streaming of the Z-line, presence of large hyaline structures, excessive accumulation of myotilin and other ectopically expressed proteins and prominent congophilic deposits.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM4 is characterized by distal and proximal muscle weakness with signs of cardiomyopathy and neuropathy.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM5 is characterized by onset in adulthood, clinical features of a limb-girdle myopathy, and focal myofibrillar destruction.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM6 is characterized by early-onset of severe, progressive, diffuse muscle weakness associated with cardiomyopathy, severe respiratory insufficiency during adolescence, and a rigid spine in some patients.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM7 is an autosomal recessive form, clinically characterized by early childhood onset of slowly progressive muscle weakness and mild atrophy primarily affecting the lower limbs, associated with joint contractures.
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM8 is an autosomal recessive form, clinically characterized by slowly progressive symmetrical weakness affecting both proximal and distal muscles, with normal to moderately elevated creatine kinase. Mild facial weakness, a high palate, nasal speech, and swallowing difficulties are typical features, mild restrictive lung disease is common, and late-onset cardiac involvement may be present.
Myopathy, myofibrillar, 9, with early respiratory failure
Hereditary myopathy with early respiratory failure
Myopathy, distal, with early respiratory failure, autosomal dominant
Myopathy, proximal, with early respiratory muscle involvement
An autosomal dominant myopathy characterized by adulthood onset of weakness in proximal, distal, axial and respiratory muscles. Pelvic girdle weakness, foot drop and neck weakness are the main symptoms at onset, but ultimately the weakness usually involves the proximal compartment of both upper and lower limbs. Additional features include variable degrees of Achilles tendon contractures, spinal rigidity and muscle hypertrophy. Respiratory involvement often leads to requirement for non-invasive ventilation support.
Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related
MFM fatal infantile hypertonic alpha-B crystallin-related
A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFMFIH-CRYAB has onset in the first weeks of life after a normal neonatal period. Affected infants show rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years.
Myopathy, myosin storage, autosomal dominant
Hyaline body myopathy autosomal dominant
A rare congenital myopathy characterized by subsarcolemmal hyalinized bodies in type 1 muscle fibers.
Myopathy, myosin storage, autosomal recessive
Myopathy, hyaline body, autosomal recessive
An autosomal recessive form of myosin storage myopathy, a muscle disease characterized by subsarcolemmal accumulation of hyalinized bodies in type 1 muscle fibers. MSMB clinical features include muscle weakness, type II respiratory failure and cardiac failure, due to hypertrophic cardiomyopathy.
Myopathy, proximal, with ophthalmoplegia
Inclusion body myopathy 3, autosomal dominant
Myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles
A muscular disorder characterized by mild-to-moderate muscle weakness, ophthalmoplegia, and contractures at birth in some patients. Muscle biopsies from patients show predominance of type 1 fibers and small or absent type 2A fibers. The disease is non-progressive or it progresses very slowly. Inheritance is autosomal dominant or recessive.
An autosomal dominant muscular disorder characterized by progressive muscle weakness with initial scapulo-humeral-peroneal and distal distribution. Over time, muscle weakness progresses to proximal muscle groups. Clinical characteristics include scapular winging, mild lower facial weakness, foot drop due to foot eversion and dorsiflexion weakness, and selective muscle atrophy. Age at onset and disease progression are variable.
A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness.
A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. TAM2 patients have myopathy and pupillary abnormalities.
Myopathy, vacuolar, with CASQ1 aggregates
An autosomal dominant mild muscle disorder characterized by adult onset of muscle cramping and weakness as well as increased levels of serum creatine kinase. The disorder is not progressive, and some patients may be asymptomatic.
Myopathy, X-linked, with excessive autophagy
A muscle disorder characterized by childhood early onset of a slowly progressive proximal limb muscle weakness (especially in legs) and elevation of serum creatine kinase, without evidence of cardiac, respiratory or central nervous system involvement. Histopathological analysis reveals diseased muscle fibers that are not necrotic, but show abnormal autophagic vacuolation as a manifestation of excessive autophagic activity in skeletal muscle cells.
Myopathy, X-linked, with postural muscle atrophy
A progressive muscular dystrophy with onset in adulthood. Affected individuals develop a proximal myopathy characterized by specific atrophy of postural muscles, limited neck flexion, bent spine, contractures of the Achilles tendon, respiratory problems, and cardiomyopathy. Patients may show muscle hypertrophy in the early stages of the disorder.
A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far.
A form of myopia, a refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. MYP26 is characterized by typical tigroid fundus changes commonly seen in early onset high myopia, and an unusual pattern of X-linked female-limited inheritance.
A form of myopia, a refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. MYP27 patients are affected by early-onset high myopia with increased axial lengths. Fundus changes include optic nerve head crescent and tigroid appearance of the posterior retina.
A form of myopia, a refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. MYP28 patients are affected by early-onset high myopia in the first decade of life. Retinal detachment may occur, and early-onset cataract has been reported.
Myopia, high, with cataract and vitreoretinal degeneration
A disorder characterized by severe myopia with variable expressivity of cataract and vitreoretinal degeneration. Some patients manifest lens subluxation, lens instability and retinal detachment.
A condition characterized by chronic inflammation of skeletal muscle with hyperplasia of the interstitial connective tissue. The clinical picture includes slender muscles with firm 'woody' consistency and restriction of movement of many joints because of muscle contractures.
A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal dominant form (Thomsen disease) is less common and less severe than the autosomal recessive one (Becker disease). A milder form of autosomal dominant myotonia is characterized by isolated myotonia without muscle weakness, hypotrophy, or hypertrophy (myotonia levior).
A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal recessive form (Becker disease) is more severe than the autosomal dominant one (Thomsen disease).
Myotonia congenita acetazolamide-responsive
A phenotypically highly variable myotonia aggravated by potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. Myotonia SCN4A-related includes myotonia permanens and myotonia fluctuans. In myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by exercise.
A soft tissue tumor that tends to occur in the limbs (especially the thigh) of patients ranging in age from 35 to 55 years. It is defined by the presence of a hypocellular spindle cell proliferation set in a myxoid background, often with mucin pooling. Lipoblasts tend to be small and often monovacuolated and to cluster around vessels or at the periphery of the lesion.
A metabolic disorder resulting in truncal ataxia, marked developmental delay, seizures, and secondary microcephaly.
Hyperammonemia due to N-acetylglutamate synthetase deficiency
Rare autosomal recessively inherited metabolic disorder leading to severe neonatal or late-onset hyperammonemia without increased excretion of orotic acid. Clinical symptoms are somnolence, tachypnea, feeding difficulties, a severe neurologic presentation characterized by uncontrollable movements, developmental delay, visual impairment, failure to thrive and hyperammonemia precipitated by the introduction of high-protein diet or febrile illness.
An enzymatic deficiency resulting in postnatal growth failure with severe delays and dysmorphic features. It is clinically characterized by wrinkled forehead, prominent eyes, widely opened anterior and posterior fontanels, downsloping palpebral fissures, thickened lids, large ears, flared nares, hypoplastic alae, short columella, protruding upper lip, and microretrognathia. There are also delayed closing of fontanels and broad great toes. Skin is characterized by redundancy or laxity with minimal subcutaneous fat, cutaneous capillary malformations, and very fine hair and eyebrows. Death results from cardiogenic shock following arrhythmia.
Neurodevelopmental disorder with microcephaly and dysmorphic facies
An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show congenital microcephaly and dysmorphic facial features, including round face, small palpebral fissures, highly arched eyebrows, and short nose.
Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies
An autosomal dominant disorder characterized by global developmental delay apparent from birth, impaired intellectual development, speech delay, dysmorphic facial features, and additional anomalies including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities.
Naegeli-Franceschetti-Jadassohn syndrome
A rare autosomal dominant form of ectodermal dysplasia. The cardinal features are absence of dermatoglyphics (fingerprints), reticular cutaneous hyperpigmentation (starting at about the age of 2 years without a preceding inflammatory stage), palmoplantar keratoderma, hypohidrosis with diminished sweat gland function and discomfort provoked by heat, nail dystrophy, and tooth enamel defects.
Nail disorder, non-syndromic congenital, 1
Nail disorder, non-syndromic congenital, 10
An autosomal recessive nail disorder characterized by a variable degree of onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals. No other anomalies of ectodermal tissues, including hair, teeth, sweat glands, or skin, are noted, and individuals with dysplastic nails have normal hearing and normal psychomotor development.
Nail disorder, non-syndromic congenital, 3
A nail disorder characterized by a white appearance of the nail plate (true leukonychia), the nail bed (pseudoleukonychia), or neither (apparent leukonychia). Leukonychia may involve all of the nail (leukonychia totalis) or only part of the nail (leukonychia partialis), or can appear as one or more transverse bands (leukonychia striata) or white spots (leukonychia punctata).
Nail disorder, non-syndromic congenital, 4
A nail disorder characterized by congenital anonychia or its milder phenotypic variant hyponychia. Anonychia/hyponychia is the absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies.
Nail disorder, non-syndromic congenital, 8
Isolated toenail dystrophy without skin fragility
A nail disorder characterized by isolated toenail dystrophy. The nail changes are most severe in the great toes and consist of the nail plate being buried in the nail bed with a deformed and narrow free edge.
Disease that cause abnormal skeletal patterning and renal dysplasia.
Rare X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, intellectual disability. Distinctive dental anomalies are seen in affected males, including supernumerary incisors and crown shaped permanent teeth. Characteristic facial features are anteverted pinnae, long face, and prominent nasal bridge and nose. Carrier females display milder variable symptoms of disease with lens opacities often involving the posterior Y sutures, and on occasion dental anomalies and the characteristic facial features described.
Rare autosomal recessive disorder of eye development characterized by extreme hyperopia and small functional eyes.
A rare disorder of eye development characterized by extreme hyperopia (farsightedness) and small functional eyes. The cornea and lens are normal in size and shape. Hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina.
Neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed.
A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and papillary adenocarcinoma.
Cardiomyopathy, arrhythmogenic right ventricular, with skin, hair, and nail abnormalities
Keratosis palmoplantaris with arrythmogenic cardiomyopathy
Palmoplantar keratoderma with arrhythmogenic right ventricular cardiomyopathy and woolly hair
Woolly hair, palmoplantar keratoderma, and cardiac abnormalities
An autosomal recessive disorder characterized by the association of diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiac abnormalities such as dilated cardiomyopathy and arrhythmogenic right ventricular dysplasia.
Nemaline myopathy 1 autosomal dominant or recessive
A form of nemaline myopathy with autosomal dominant or recessive inheritance. Nemaline myopathies are disorders characterized by muscle weakness of varying onset and severity, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Autosomal dominant NEM1 is characterized by a moderate phenotype with onset between birth and early second decade of life. Weakness is diffuse and symmetric with slow progression often with need for a wheelchair in adulthood. The autosomal recessive form has onset at birth with moderate to severe hypotonia and diffuse weakness. In the most severe cases, death can occur before 2 years. Less severe cases have delayed major motor milestones, and these patients may walk, but often need a wheelchair before 10 years.
An autosomal recessive severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM10 is characterized by early-onset generalized muscle weakness and hypotonia with respiratory insufficiency and feeding difficulties. Additional features include arthrogryposis or congenital contractures, ophthalmoplegia, a history of prematurity, reduced fetal movements, and polyhydramnios. Most patients die of respiratory failure in early infancy.
Nemaline myopathy 11, autosomal recessive
An autosomal recessive form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM11 is characterized by slowly progressive muscle weakness and atrophy, mainly affecting the lower limbs and neck. Some patients may have mild cardiac or respiratory involvement, but they do not have respiratory failure.
A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination.
Nemaline myopathy 3 with intranuclear rods
A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 4 presents from infancy to childhood with hypotonia and moderate-to-severe proximal weakness with minimal or no progression. Major motor milestones are delayed but independent ambulation is usually achieved, although a wheelchair may be needed in later life.
A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 5 is a severe and progressive form common among Old Order Amish. Affected infants display tremors with hypotonia and mild contractures of the shoulders and hips. Proximal contractures progressively weaken and a pectus carinatum deformity develops before children die of respiratory insufficiency, usually in the second year.
A form of nemaline myopathy characterized by childhood onset of slowly progressive proximal muscle weakness, exercise intolerance, and slow movements with stiff muscles. Patients are unable to run or correct themselves from falling over.
Nemaline myopathy 7, autosomal recessive
A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 7 presents at birth with hypotonia and generalized weakness. Major motor milestones are delayed, but independent ambulation is achieved.
Nemaline myopathy 8, autosomal recessive
A severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM8 is characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils.
An autosomal recessive form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM9 phenotype is highly variable, ranging from death in infancy due to lack of antigravity movements, to slowly progressive distal muscle weakness with preserved ambulation later in childhood.
Nephrogenic syndrome of inappropriate antidiuresis
Characterized by an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolarity, and natriuresis.
A form of nephrolithiasis, a condition in which urinary supersaturation leads to stone formation in the urinary system. Patients manifest acute renal colic with severe pain originating in the flank. Patients with small, non-obstructing stones or those with staghorn calculi may be asymptomatic. The majority of renal calculi contain calcium. CAON is characterized by calcium oxalate kidney stones.
Nephrolithiasis, X-linked recessive, with renal failure
An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XRN patients present with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia.
Nephrolithiasis/osteoporosis, hypophosphatemic, 1
A disease characterized by decreased renal phosphate absorption, renal phosphate wasting, hypophosphatemia, hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis.
Nephrolithiasis/osteoporosis, hypophosphatemic, 2
An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years.
A disorder characterized by the association of nephronophthisis with hepatic fibrosis. Nephronophthisis is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical features are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms, especially ocular lesions, are frequent.
An autosomal recessive disorder resulting in end-stage renal disease. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Some patients manifest extra-renal features including retinal, skeletal and central nervous system defects.
An autosomal recessive disorder resulting in end-stage renal disease. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
An autosomal recessive disorder manifesting as infantile-onset kidney disease, cerebellar vermis hypoplasia, and situs inversus. Nephronophthisis is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
An autosomal recessive disorder characterized by the association of nephronophthisis with Leber congenital amaurosis and retinal degeneration, often resulting in blindness during childhood. Additional features include seizures, cerebellar vermis hypoplasia, facial dysmorphism, bronchiectasis and liver failure. Nephronophthisis is a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure.
A form of nephronophthisis, a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure. Some patients have cystic kidneys of normal size and no extrarenal manifestations, whereas others have enlarged renal size and severe extrarenal defects, including hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs inversus, and periportal liver fibrosis.
An autosomal recessive disorder characterized by chronic tubulointerstitial nephritis resulting in end-stage renal disease in early childhood. Extrarenal manifestations, including intellectual disability or liver changes, may occur in some patients.
A form of nephronophthisis, an autosomal recessive disorder characterized by chronic tubulointerstitial nephritis resulting in end-stage renal disease. NPHP19 patients also manifest hepatosplenomegaly, hepatic fibrosis, destruction of the bile ducts, focal bile ductal proliferation, ductal plate malformation, and cholestasis.
An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by early onset and rapid progression. Phenotypic manifestations include enlarged kidneys, chronic tubulo-interstitial nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also display situs inversus. Pathologically, it differs from later-onset nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes, and by the presence of cortical microcysts.
A form of nephronophthisis, an autosomal recessive chronic tubulo-interstitial nephritis that progresses to end-stage renal failure. Some patients have cystic kidneys of normal size and no extrarenal manifestations, whereas others have enlarged renal size and severe extrarenal defects, including hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs inversus, and periportal liver fibrosis. NPHP20 patients do not show extrarenal manifestations or evidence of a ciliopathy, such as situs inversus or polydactyly.
An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by polyuria, polydipsia, anemia. Onset of terminal renal failure occurr significantly later (median age, 19 years) than in juvenile nephronophthisis. Renal pathology is characterized by alterations of tubular basement membranes, tubular atrophy and dilation, sclerosing tubulointerstitial nephropathy, and renal cyst development predominantly at the corticomedullary junction.
An autosomal recessive inherited disease resulting in end-stage renal disease at age ranging between 6 and 35 years. It is a progressive tubulo-interstitial kidney disorder characterized by polydipsia, polyuria, anemia and growth retardation. The most prominent histological features are modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
An autosomal recessive disorder resulting in end-stage renal disease during childhood or adolescence. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
An autosomal recessive disorder with features of nephronophthisis, a cystic kidney disease leading to end-stage renal failure. Nephronophthisis is histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical manifestation are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms are frequent. In NPHPL1 patients, extrarenal symptoms include hypertension, essential tremor, sensorineural hearing loss and gout. Severely affected individuals can manifest a mitochondrial disorder with isolated complex I deficiency activity in muscle, seizures, intellectual disability and hypertrophic dilated cardiomyopathy.
A disorder with features of nephronophthisis, a cystic kidney disease leading to end-stage renal failure. Nephronophthisis is histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical manifestation are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms are frequent. NPHPL2 is an autosomal recessive form characterized by onset of progressive renal insufficiency in the first decades of life.
Congenital nephrotic syndrome of the Finnish type
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure.
A form of nephrotic syndrome, a renal disease clinically characterized by focal segmental glomerulosclerosis, progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. NPHS10 is a steroid-sensitive form characterized by onset in childhood and remission without end-stage kidney disease.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. NPHS11 is an autosomal recessive, steroid-resistant and progressive form with onset in the first decade of life.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. NPHS12 inheritance is autosomal recessive.
Sphingosine phosphate lyase insufficiency syndrome
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS14 is an autosomal recessive syndromic, steroid-resistant form that progresses to end-stage renal failure. Some NPHS14 patients manifest ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS15 is an autosomal recessive form with onset in the first months of life. Disease severity is variable. Some patients show rapid progression to end-stage renal failure.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS16 inheritance is autosomal recessive.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS17 is an autosomal recessive, steroid-resistant progressive form with onset in the first decade of life.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS18 is an autosomal recessive, steroid-resistant progressive form with onset in the first decade of life.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS19 is an autosomal recessive, steroid-resistant form with onset in the first or second decade of life, resulting in chronic kidney disease.
Autosomal recessive steroid-resistant nephrotic syndrome
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. The disorder is resistant to steroid treatment and progresses to end-stage renal failure in the first or second decades. Some patients show later onset of the disorder.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS20 is an X-linked, steroid-resistant form with onset at birth or in the first years of life in affected males. Death in childhood may occur in absence of renal transplantation. Carrier females may be unaffected or have a mild disease with proteinuria.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS21 is an autosomal recessive, rapidly progressive, steroid-resistant form characterized by onset of kidney dysfunction in the first year of life. Some patients may have variable extra-renal manifestations.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS22 is an autosomal recessive, steroid-resistant form characterized by onset of progressive kidney dysfunction in infancy.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS23 is an autosomal recessive form characterized by onset of proteinuria in the first or second decade of life, and variable outcome. Some patients have normal renal function after many years, whereas others may progress to chronic kidney disease.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS24 is an autosomal recessive, slowly progressive form. Most patients eventually develop end-stage renal disease.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS26 is an autosomal recessive form characterized by onset of proteinuria in the first months or years of life. Some patients respond to steroids, whereas others show steroid resistance and progression to end-stage renal disease.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.
Nephrotic syndrome 5 with or without ocular abnormalities
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. NPHS5 is characterized by very early onset of progressive renal failure. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.
Nephrotic syndrome type 7 with membranoproliferative glomerulonephritis
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. NPHS7 is an autosomal recessive form characterized by onset of proteinuria usually in the first decade of life. The disorder is progressive, and some patients develop end-stage renal disease within several years. Renal biopsy typically shows membranoproliferative glomerulonephritis.
A form of nephrotic syndrome, a renal disease clinically characterized by progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show diffuse mesangial sclerosis, with small glomeruli, hypercellularity, increased extracellular matrix, and contracted/collapsed glomerular tufts surrounded by immature or abnormal podocytes.
A form of nephrotic syndrome, a renal disease clinically characterized by progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show focal segmental glomerulosclerosis.
Neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment
An autosomal dominant neurodegenerative disorder with variable manifestations. Main features are delayed psychomotor development, progressive spasticity, intellectual disability, speech delay, and learning disabilities. Some patients never achieve ambulation. Additional variable features are cortical visual impairment, often associated with optic atrophy, axonal peripheral neuropathy, seizures, dysautonomia, ataxia, and dystonia. Brain imaging often shows progressive cerebellar atrophy and thin corpus callosum. Disease onset is in infancy or early childhood.
Progeria syndrome childhood-onset with osteolysis
An atypical progeroid syndrome characterized by normal development in the first years of life, later followed by the emergence of generalized lipoatrophy, severe osteoporosis, and marked osteolysis. The atrophic facial subcutaneous fat pad and the marked osteolysis of the maxilla and mandible result in a typical pseudosenile facial appearance with micrognathia, prominent subcutaneous venous patterning, a convex nasal ridge, and proptosis. Cognitive development is completely normal. Patients do not have cardiovascular dysfunction, atherosclerosis, or metabolic anomalies.
Erythroderma, ichthyosiform, with hypotrichosis and hyper-IgE
An autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration.
A lethal, autosomal recessive multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, limb deformities, hypoplastic lungs, edema, and central nervous system anomalies including lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum. Abnormal facial features include severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears.
A form of Neu-Laxova syndrome, a lethal, autosomal recessive multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, limb deformities, hypoplastic lungs, edema, and central nervous system anomalies. These include lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum. Abnormal facial features include severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears.
Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components.
The most common NTDs are open spina bifida (myelomeningocele) and anencephaly.
A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.
An autosomal recessive syndrome characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with a supernumerary hypoplastic digit between the fourth and fifth digits of the hands and/or feet. Other features include eye abnormalities, hearing impairment, and electroencephalogram anomalies.
Neurodegeneration due to cerebral folate transport deficiency
An autosomal recessive neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy.
Neurodegeneration with ataxia and late-onset optic atrophy
An autosomal dominant disorder characterized by slowly progressive cerebellar and gait ataxia, optic atrophy, and myopathy or myalgia. Additional features can include cardiomyopathy, psychiatric disturbances, and peripheral sensory impairment. Disease onset is usually in mid-adulthood.
Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset
A neurodegenerative disorder characterized by gait abnormalities, ataxia, dysarthria, dystonia, vertical gaze palsy, and cognitive decline. Disease onset is in childhood or adolescence. NADGP transmission pattern is consistent with autosomal recessive inheritance.
Neurodegeneration with brain iron accumulation 1
Pantothenate kinase-associated neurodegeneration
PKAN neuroaxonal dystrophy juvenile-onset
Autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. Clinical manifestations include progressive muscle spasticity, hyperreflexia, muscle rigidity, dystonia, dysarthria, and intellectual deterioration which progresses to severe dementia over several years. It is clinically classified into classic, atypical, and intermediate phenotypes. Classic forms present with onset in first decade, rapid progression, loss of independent ambulation within 15 years. Atypical forms have onset in second decade, slow progression, maintenance of independent ambulation up to 40 years later. Intermediate forms manifest onset in first decade with slow progression or onset in second decade with rapid progression. Patients with early onset tend to also develop pigmentary retinopathy, whereas those with later onset tend to also have speech disorders and psychiatric features. All patients have the 'eye of the tiger' sign on brain MRI.
Neurodegeneration with brain iron accumulation 2A
A neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years.
Neurodegeneration with brain iron accumulation 2B
Neurodegeneration with brain iron accumulation PLA2G6-related
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by progressive extrapyramidal dysfunction leading to rigidity, dystonia, dysarthria and sensorimotor impairment.
Neurodegeneration with brain iron accumulation 3
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild non-progressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.
Neurodegeneration with brain iron accumulation 4
Mitochondrial membrane protein associated neurodegeneration
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA4 results in speech difficulty, extrapyramidal signs, oromandibular and generalized dystonia, and parkinsonism. Most patients have progressive involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor plantar responses.
Neurodegeneration with brain iron accumulation 5
Beta-propeller protein-associated neurodegeneration
Static encephalopathy of childhood with neurodegeneration in adulthood
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA5 is characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability.
Neurodegeneration with brain iron accumulation 6
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by progressive motor and cognitive dysfunction beginning in childhood or young adulthood. Patients show extrapyramidal motor signs, such as spasticity, dystonia, and parkinsonism.
Neurodegeneration with brain iron accumulation 7
A neurodegenerative disorder associated with iron accumulation, primarily in the basal ganglia. Clinical features include speech and motor delay, truncal hypotonia, progressive cerebellar ataxia, and loss of ambulation. NBIA7 transmission pattern is consistent with autosomal recessive inheritance.
Neurodegeneration with brain iron accumulation 8
A neurodegenerative disorder associated with iron accumulation, primarily in the basal ganglia. Disease onset is in early childhood. Clinical features include speech delay, progressive cerebellar ataxia, unbalanced gait, and loss of ambulation. NBIA8 transmission pattern is consistent with autosomal recessive inheritance.
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures
An autosomal recessive neurodegenerative disorder characterized by pediatric onset of progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections.
Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline
An autosomal recessive neurodegenerative disease characterized by progressive ataxia, tremor, cognitive decline, dysphagia, optic atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrates cerebellar atrophy and leukoencephalopathy.
Neurodegeneration, childhood-onset, with brain atrophy
An autosomal dominant neurodegenerative disease with onset in childhood, characterized by progressive cortical atrophy, developmental delay, developmental regression, loss of motor skills and ambulation, absence of language, and intellectual disability.
Neurodegeneration, childhood-onset, with cerebellar atrophy
An autosomal recessive disorder characterized by early onset of progressive neurodegeneration affecting the central and peripheral nervous systems. Clinical features include global developmental delay, impaired intellectual development, poor or absent speech, and motor abnormalities. Brain imaging shows cerebellar atrophy. Death in childhood may occur.
Neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities
An autosomal dominant, progressive, neurodegenerative disorder characterized by severe global developmental delay, impaired intellectual development, poor or absent speech, hypotonia, impaired motor development, respiratory insufficiency, and feeding difficulties. Most patients have visual defects, including cortical visual blindness, nystagmus, and esotropia. Brain imaging shows abnormalities affecting the brainstem, cerebellum, and corticospinal tracts. Disease onset is in infancy or early childhood.
Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
An autosomal recessive disorder characterized primarily by global developmental delay and variably impaired intellectual development with speech delay apparent from infancy. Affected individuals have hypotonia, poor feeding, poor overall growth, and respiratory distress early in life. Other features include visual impairment due to optic atrophy, sensorineural hearing loss, and neuromuscular abnormalities. Features suggestive of a mitochondrial disorder include cataracts, cardiomyopathy, diabetes mellitus, combined oxidative phosphorylation deficiency, and increased lactate. Some patients develop seizures, some have dysmorphic facial features, and some have non-specific abnormalities on brain imaging. Death in childhood may occur.
Neurodegeneration, childhood-onset, with progressive microcephaly
An autosomal recessive disorder characterized by global developmental delay apparent from infancy. Most severely affected individuals have severe and progressive microcephaly, early-onset seizures, lack of visual tracking, and almost no developmental milestones, resulting in early death. Less severely affected individuals have a small head circumference and severely impaired intellectual development with poor speech and motor delay. Additional features may include poor overall growth, axial hypotonia, limb hypertonia with spasticity, undescended testes, and cerebral atrophy with neuronal loss.
Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia
An autosomal recessive disorder characterized by severe neurological and extra-neurological manifestations. Clinical features include early-onset global developmental delay, absent speech, dystonia, spasticity, choreoathetoid movement disorder, seizures, and microcytic hypochromic anaemia unresponsive to iron supplementation.
Neurodevelopmental disorder and language delay with or without structural brain abnormalities
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay with onset in infancy and additional variable features including hypotonia, epilepsy, brain abnormalities such as ventriculomegaly and a small corpus callosum, and autism spectrum disorder.
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity
An autosomal recessive disorder characterized by global developmental delay, brain abnormalities, mainly ventriculomegaly and/or brain atrophy, intellectual disability, absent speech, peripheral spasticity, and microcephaly. Additional variable features include early-onset seizures, optic atrophy, and dysmorphic facial features. Early death may occur.
Neurodevelopmental disorder with absent language and variable seizures
A disorder characterized by neurodevelopmental abnormalities, including moderate to profound intellectual disability, with autistic features, seizures, severe impairments in speech, and gross motor delay.
Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly
An autosomal recessive neurodevelopmental disorder characterized by intellectual disability, microcephaly, ataxia, and muscular hypotonia.
Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter
An autosomal dominant neurodevelopmental disorder apparent in infancy and characterized by severe intellectual disability with absent speech, epilepsy, and hypotonia. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly can be present. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem.
Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia
An autosomal recessive disorder characterized by global developmental delay with severely impaired intellectual development, impaired motor development, axial and peripheral hypotonia, poor speech and significant behavioral abnormalities, including autism spectrum disorder, hyperactivity, mood disorders, aggression, hand and face stereotypies, sleep disturbances, anxiety, self-injurious behavior, and bruxism.
Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, and speech delay apparent from infancy or early childhood. Most patients have dysmorphic facial features, and white matter abnormalities on brain imaging. More variable features may include teeth anomalies, distal joint contractures, spasticity, peripheral neuropathy, and behavioral problems.
Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies
An autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, impaired intellectual development, hypotonia, brain anomalies including cortical volume loss, corpus callosum dysgenesis and cerebellar hypoplasia, and variable dysmorphic features. Patients may have platyspondyly, scoliosis, and cardiac anomalies.
Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis
Glycosylphosphatidylinositol biosynthesis defect 21
An autosomal recessive disorder characterized by global developmental delay, severe-to-profound intellectual disability, muscular hypotonia, seizures, brain anomalies, including thin corpus callosum and cerebellar atrophy, scoliosis, and mild facial dysmorphism.
Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, moderate to severe intellectual disability, spastic paraparesis, ataxia, and/or peripheral neuropathy. Patients also exhibit dysmorphic features and congenital microcephaly. Most affected individuals develop progressive hypertrophic cardiomyopathy in childhood or have cardiac developmental anomalies. Brain imaging shows corpus callosum abnormalities in all patients, and perisylvian polymicrogyria-like pattern in some individuals.
Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies
An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay with motor impairment, cognitive delays, absent or severely limited speech, dysmorphic features, hypotonia and cataracts.
Neurodevelopmental disorder with central and peripheral motor dysfunction
An autosomal recessive neurodevelopmental disorder with early onset and a highly variable phenotype. Disease features include hypotonia apparent from birth, poor feeding, global developmental delay with absence of reaction to touch and no eye contact, infantile-onset progressive ataxia and demyelinating peripheral neuropathy.
Neurodevelopmental disorder with central hypotonia and dysmorphic facies
An autosomal dominant disease characterized by global developmental delay, impaired intellectual development, seizures, distinctive facial features, scoliosis, delayed closure of the anterior fontanel, and non-specific brain abnormalities.
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction
An autosomal recessive disorder characterized by global developmental delay with predominantly motor abnormalities, axial hypotonia with decreased or absent reflexes, gait ataxia and appendicular spasticity. Affected individuals have cognitive impairment and speech delay. Brain imaging shows cerebellar atrophy.
Neurodevelopmental disorder with cerebellar atrophy and with or without seizures
An autosomal recessive disorder characterized by psychomotor developmental delay manifesting in infancy, cerebellar atrophy, decreased myelination, and seizures in most patients. Additional features include intellectual disability, ataxia or dyspraxia, hypertonia, hyperreflexia, poor or absent speech, microcephaly, subtle dysmorphisms, and visual impairment in some patients.
Neurodevelopmental disorder with cerebellar hypoplasia and spasticity
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, profound intellectual disability, seizures, absent speech, spasticity, facial and limb dysmorphism, and subtle structural brain abnormalities including cerebellar hypoplasia.
Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism
An autosomal recessive disorder characterized by global developmental delay apparent from birth, moderate-to-severe intellectual disability, poor or absent speech, and hypotonia. Most patients have variable dysmorphic facial features. Brain imaging shows corpus callosum agenesis, mild ventriculomegaly, simplified gyral pattern, and cerebral atrophy.
Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities
An autosomal dominant disorder characterized by global developmental delay, variable intellectual disability, poor language acquisition, and dysmorphic facial features including a prominent nasal bridge and coarse features. Some patients manifest autism spectrum disorder. Musculoskeletal features may be present and include widened and thickened hands and fingers, joint hypermobility, clinodactyly of the fifth fingers, and toe syndactyly.
Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects
An autosomal dominant disorder characterized by global developmental delay, severely impaired intellectual development with poor or absent speech, characteristic dysmorphic facial features, and variable skeletal abnormalities. Additional features include feeding difficulties, inability to walk or walking with an abnormal gait, and cerebellar or other abnormalities on brain imaging.
Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia
An autosomal recessive disorder characterized by global developmental delay, intellectual disability, facial dysmorphism, and abnormalities of the cerebellum observed on brain imaging. Disease severity is variable. Some affected individuals have poor overall growth with microcephaly, delayed walking, spasticity, and poor or absent speech. Others may achieve more significant developmental milestones. Additional variable manifestations may include cardiac ventricular septal defect, spasticity, cataracts, optic nerve hypoplasia, seizures, and joint contractures.
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
An autosomal dominant neurodevelopmental disorder characterized by variable degrees of developmental delay, intellectual disability, speech delay, postnatal microcephaly, dysmorphic features, and mild abnormalities of the hands and feet.
Neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies
An autosomal dominant disorder characterized by intellectual disability, developmental delay, poor language acquisition, behavioral abnormalities, growth failure, feeding difficulties, microcephaly, facial dysmorphism, and mild skeletal anomalies of the hands and feet.
Neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia
An autosomal recessive disorder characterized by moderate to severe global developmental delay, facial dysmorphism, and ischiopubic synchondrosis hypoplasia. Affected individuals show infection-triggered lymphopenia, and loss of developmental milestones associated with epileptic spasms. Diminished white matter volume, enlarged ventricles, and thin corpus callosum are visible on brain imaging.
Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities
An autosomal dominant disorder characterized by global developmental delay with impaired intellectual development and poor or absent speech, corpus callosum structural defects and cerebellar hypoplasia on brain imaging, poor overall growth, facial dysmorphism, and skeletal defects. Variable additional findings include hypotonia, seizures, and ocular defects.
Neurodevelopmental disorder with dysmorphic facies and thin corpus callosum
An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development with poor or absent speech and language, and autistic-like behaviors. Corpus callosum anomalies are visible on brain imaging. Most patients have dysmorphic features including tall forehead, down-slanting palpebral fissures, ear anomalies and broad nasal bridge. Other variably present clinical features include seizures, sleeping difficulties and precocious puberty.
Neurodevelopmental disorder with dysmorphic facies and variable seizures
An autosomal recessive disorder characterized by global developmental delay apparent in early childhood, mildly impaired intellectual development, speech delay, behavioral abnormalities, and non-specific dysmorphic facial features. Some patients may have seizures, brain imaging abnormalities, mild skeletal defects, and renal abnormalities.
Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia
An autosomal recessive disorder characterized by global developmental delay, mildly to severely impaired intellectual development, poor speech and language acquisition. Some patients may have early normal development with onset of the disorder in the first years of life. More variable neurologic abnormalities include hypotonia, seizures, apnea, mild signs of autonomic or peripheral neuropathy, and autism.
Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities
A neurodevelopmental disorder characterized by severe global developmental delay, intellectual disability, poor or absent language, behavioral abnormalities, severe sleep disturbance, seizures, cerebral malformations, and craniofacial dysmorphism. Progressive cerebellar atrophy is also observed. Additional features may include genitourinary tract anomalies, hearing loss, and mild distal skeletal defects.
Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities
Glycosylphosphatidylinositol biosynthesis defect 9
An autosomal recessive disorder characterized by severely delayed global development, with hypotonia, impaired intellectual development, and poor or absent speech. Most patients have spasticity with limb hypertonia and brisk tendon reflexes. Additional features include non-specific dysmorphic facial features, structural brain abnormalities, and cortical visual impairment.
Neurodevelopmental disorder with dystonia and seizures
An autosomal recessive disorder characterized by global developmental delay, inability to walk or speak, profoundly impaired intellectual development, and early-onset dystonia. Additional features may include other extrapyramidal movements, seizures or seizure-like activity, and cerebellar hypoplasia on brain imaging.
Neurodevelopmental disorder with epilepsy and brain atrophy
An autosomal recessive disorder characterized by global developmental delay, early-onset progressive myoclonus epilepsy and ataxia. Brain imaging shows progressive atrophy.
Neurodevelopmental disorder with epilepsy and hemochromatosis
An X-liked recessive disorder characterized by severe developmental delay, intellectual disability, early-onset epilepsy, and early systemic iron overload resulting in juvenile-onset hemochromatosis. Variable additional features may include joint contractures, visual or hearing impairment, and skin abnormalities.
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum
An autosomal recessive disorder characterized by severe psychomotor delay, intellectual disability, hypotonia, epilepsy, and corpus callosum hypoplasia. Some patients show mild cerebellar hypoplasia and atrophy.
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
A neurodevelopmental disorder characterized by microcephaly, profound developmental delay, intellectual disability, cataracts, severe epilepsy including infantile spasms, irritability, failure to thrive, and stereotypic hand movements. Brain imaging reveals delayed myelination and cerebral atrophy.
Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy
An autosomal recessive disorder characterized by severely impaired global development apparent soon after birth, early-onset seizures, lack of psychomotor development, spastic quadriparesis, progressive cortical and cerebellar atrophy, and dysmorphic features, including microcephaly. Death in childhood may occur.
Neurodevelopmental disorder with eye movement abnormalities and ataxia
An autosomal dominant disorder apparent from infancy and characterized by global developmental delay, intellectual disability, speech difficulties, ataxia, seizures, and abnormalities of eye movement.
Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly
An autosomal recessive disorder with onset in infancy and characterized by global developmental delay, intellectual disability, dysmorphic facial features, coarse facies, and behavioral problems. Affected individuals may have variable findings on brain imaging, such as cortical atrophy, thin corpus callosum and enlarged ventricles. Laboratory studies show nuclear lobulation defects in a subset of neutrophils, indicating a pseudo-Pelger-Huet anomaly.
Neurodevelopmental disorder with feeding difficulties, thin corpus callosum, and foot deformity
An autosomal recessive disorder characterized by impaired intellectual development, microcephaly, delayed psychomotor development, pyramidal signs, thin corpus callosum, and foot deformity.
Neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked
A neurodevelopmental disorder characterized by hypotonia, abnormal gait, developmental delay, intellectual disability especially affecting expressive language, and autistic behavior. Additional features include facial dysmorphism,ocular anomalies, and gastrointestinal issues. Rare patients have seizures. Disease severity is variable. Males tend to be more severely affected than females.
Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities
An autosomal recessive neurodevelopmental disorder characterized by developmental delay, intellectual disability, and absent speech. Patients have microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Neurodevelopmental disorder with hearing loss and spasticity
An autosomal recessive neurodevelopmental disorder characterized by hearing loss, global developmental delay, impaired intellectual development, hypotonia, spastic-dystonic cerebral palsy, focal or generalized epilepsy, and microcephaly.
Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities
An autosomal recessive disorder characterized by intellectual disability, intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss.
Neurodevelopmental disorder with hyperkinetic movements and dyskinesia
An autosomal recessive disorder characterized by severe global developmental delay, axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements.
Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements
An autosomal dominant disorder characterized by axial hypotonia apparent at birth, global developmental delay, intellectual disability, seizures, and autistic features. Involuntary hyperkinetic movements are present in some patients.
Neurodevelopmental disorder with hypotonia and brain abnormalities
An autosomal dominant disorder characterized by onset in infancy or early childhood, global developmental delay, hypotonia, impaired intellectual development, and poor or absent speech. Additional variable manifestations may be present, including feeding difficulties, seizures, behavioral abnormalities, and non-specific dysmorphic facial features. Brain imaging shows variable abnormalities, including corpus callosum and cerebellar defects, and decreased white matter volume.
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures
Glycosylphosphatidylinositol biosynthesis defect 22
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, intellectual disability, hypotonia, cerebellar ataxia, cerebellar atrophy, delayed motor skills, poor or absent speech, and epilepsy in most patients. Some patients manifest facial dysmorphism. Disease onset is in infancy.
Neurodevelopmental disorder with hypotonia and dysmorphic facies
An autosomal dominant disorder characterized by global developmental delay, hypotonia, and variably impaired intellectual development, often with speech delay and delayed walking. Most patients have dysmorphic facial features. Clinical features are highly variable and may include congenital cardiac defects, non-specific renal anomalies, joint contractures or joint hyperextensibility, dry skin, and cryptorchidism.
Neurodevelopmental disorder with hypotonia and gross motor and speech delay
An autosomal recessive disorder characterized by severe global developmental delay apparent from infancy, axial hypotonia, limited or absent ability to walk, impaired intellectual development, and poor or absent speech. Additional features may include seizures, behavioral problems, distal skeletal anomalies, and facial dysmorphism.
Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
An autosomal dominant neurodevelopmental disorder characterized by profound infantile-onset hypotonia, developmental delay with poor speech, delayed walking, and impaired intellectual development. Additional variable features include feeding difficulties, dysmorphic features, and visual defects.
Neurodevelopmental disorder with hypotonia, craniofacial abnormalities, and seizures
Psychomotor retardation, epilepsy, and craniofacial dysmorphism
An autosomal recessive disease characterized by severe psychomotor retardation, intractable seizures, dysmorphic features, and a lumpy skull surface. Patients are hypotonic and have poor feeding in the neonatal period.
Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities
An autosomal recessive neurodevelopmental disorder characterized by severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures may be present in affected individuals.
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities
An autosomal recessive disorder characterized by global developmental delay, severely impaired intellectual development, hypotonia, coarse facial features, and muscle weakness, often resulting in the inability to walk or sit. Additional features include feeding difficulties, respiratory distress, scoliosis, poor visual function, and rotary nystagmus. Brain imaging shows variable abnormalities, including enlarged ventricles, decreased white matter volume, white matter changes, thin corpus callosum, and cerebellar hypoplasia.
Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures
Dyskinesia, seizures, and intellectual developmental disorder
An autosomal recessive disorder characterized by psychomotor delay, epilepsy, intellectual disability, speech impairment and dyskinesia of the limbs. Patients also manifest autistic features and other behavioral abnormalities.
Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities
An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, delayed or absent speech, hypotonia, behavioral abnormalities, and epilepsy that ranges from self-limiting to intractable. More variable features include non-specific dysmorphic facial features, distal skeletal anomalies, and brain imaging abnormalities.
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
An autosomal dominant disorder characterized by global developmental delay apparent from infancy, intellectual disability, poor or absent speech, behavioral abnormalities, and hypotonia with delayed walking or inability to walk. Additional features include epilepsy, mild skeletal defects, and non-specific dysmorphic features.
Neurodevelopmental disorder with hypotonia, microcephaly, and seizures
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay with axial hypotonia, inability to sit or walk, impaired intellectual development with absent language, and early-onset intractable seizures in most patients. Additional features include poor overall growth, microcephaly, dysmorphic features, poor eye contact due to cortical blindness, and non-specific brain abnormalities.
Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation
An autosomal recessive disorder characterized by profound neurodevelopmental disability, muscular hypotonia, feeding abnormalities, recurrent fever episodes, infantile spasms, and moderate dysmorphic facial features. Brain imaging shows thin corpus or dysplastic corpus callosum, and additional unspecific abnormalities including gray matter heterotopias, ectopic posterior pituitary, signal abnormalities in basal ganglia, and stratum subependymale.
Neurodevelopmental disorder with hypotonia, neuropathy, and deafness
Myopathy, congenital, with neuropathy and deafness
An autosomal recessive disorder characterized by congenital myopathy with hypotonia and muscle weakness manifesting after birth and progressing to generalized muscle atrophy, central deafness with absent brainstem-evoked potentials, and a combined axonal and demyelinating motor neuropathy.
Neurodevelopmental disorder with hypotonia, seizures, and absent language
A neurodevelopmental disorder characterized by severely delayed psychomotor development, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly. Brain imaging show cerebral atrophy, enlarged ventricles, and white matter abnormalities.
Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language
An autosomal dominant disorder characterized by impaired intellectual development, absent speech, hypotonia, poor eye contact and stereotypic movements. Dysmorphic features include high broad forehead with variable small chin, short nose with anteverted nares, large open mouth, upslanted palpebral fissures and prominent eyebrows. Some patients have seizures.
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia
An autosomal recessive disease characterized by global developmental delay, hypotonia, ataxic gait, hyporeflexia, poor or absent speech, and variable and mild dysmorphic features.
Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
An autosomal dominant disorder characterized by axial hypotonia and global developmental delay. Affected individuals show impaired intellectual development, delayed walking, poor speech, and behavioral abnormalities. Some patients have a more severe phenotype with early-onset seizures resembling epileptic encephalopathy, inability to walk or speak, and hypomyelination on brain imaging.
Neurodevelopmental disorder with impaired speech and hyperkinetic movements
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, delayed walking, poor or absent speech, and a hyperkinetic movement disorder with dystonia, tremor, ataxia, or chorea. Some patients develop seizures.
Neurodevelopmental disorder with infantile epileptic spasms
An autosomal dominant neurodevelopmental disorder characterized by onset of severe and frequent epileptic spasms within the first year of life. Affected individuals have global developmental delay with delayed walking and poor or absent speech. More variable features may include poor overall growth, high-arched palate, and delayed myelination on brain imaging.
Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies
An autosomal recessive disorder characterized by characterized by mild to moderate intellectual disability, dysmorphic facial features, intention tremor, dyspraxia, and vertical strabismus.
Neurodevelopmental disorder with involuntary movements
A neurodevelopmental disorder manifesting with a wide range of clinical symptoms. Clinical features range from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior and epileptic encephalopathy, to a milder phenotype featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia, and mild epilepsy. Hyperkinetic movements are often exacerbated by specific triggers, such as illness, emotion and high ambient temperature. Some patients have brain abnormalities, such as cerebral atrophy or thin corpus callosum.
Neurodevelopmental disorder with language delay and seizures
An autosomal recessive disorder characterized by global developmental delay, intellectual disability, speech delay, and seizures. Additional features may include axial hypotonia, peripheral hypertonia, hypothyroidism, and non-specific dysmorphic features or brain imaging abnormalities.
Neurodevelopmental disorder with language impairment and behavioral abnormalities
A neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and behavioral abnormalities, such as autism spectrum disorder, repetitive behaviors, and hyperactivity. Some patients develop seizures and manifest developmental regression.
Neurodevelopmental disorder with microcephaly and gray sclerae
An autosomal recessive disorder characterized by global developmental delay, hypotonia, profoundly impaired intellectual development with poor or absent language, mild microcephaly, abnormal visual fixation, and seizures in most patients. Affected individuals also have gray sclerae.
Neurodevelopmental disorder with microcephaly and structural brain anomalies
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, microcephaly, dysmorphic facial features, and cerebral malformations including simplification of cerebral gyration, agenesis of the corpus callosum, and brainstem and white matter hypoplasia.
Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies
An autosomal recessive disorder characterized by severe global developmental delay, severely impaired intellectual development with poor or absent speech, severe encephalopathy, microcephaly with simplified gyral pattern, hypomyelination, thin corpus callosum, mild cerebellar hypoplasia, brainstem hypoplasia, congenital arthrogryposis, dysmorphic features, and respiratory problems often leading to early demise.
Neurodevelopmental disorder with microcephaly, ataxia, and seizures
An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness.
Neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities
An autosomal recessive, severe neurodevelopmental disorder characterized by global developmental delay since infancy, microcephaly, poor or absent speech, and inability to walk or spasticity. Additional features include renal abnormalities, congenital cataracts, gastroesophageal reflux disease, seizures with onset in infancy or childhood, hyporeflexia, and non-specific white matter abnormalities on brain imaging.
Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
An autosomal recessive disorder characterized by global developmental delay, intellectual disability, facial dysmorphism, and microcephaly.
Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity
An autosomal recessive neurodevelopmental disorder characterized by developmental delay, severe to profound intellectual disability, congenital microcephaly, cortical polymicrogyria, lissencephaly, reduced central white matter volume, and drug-resistant epilepsy, lack of speech, absent ambulation and a progressive neurodegenerative course in most patients. Early death may occur in some patients.
Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy
An autosomal recessive neurodevelopmental disorder characterized by microcephaly, global developmental delay, hypotonia, intellectual disability, autistic features such as poor social interaction, language impairment and repetitive automatism behaviors, and generalized tonic-clonic seizures. Brain imaging shows cortical atrophy, thin corpus callosum, and cerebellar and brainstem atrophy.
Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
An autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy, and characterized by microcephaly, short stature, severe global developmental delay, progressive spasticity, and epilepsy. Brain imaging shows delayed myelination, hypomyelination, enlarged ventricles, and cerebellar atrophy.
Neurodevelopmental disorder with microcephaly, hypotonia, and absent language
An autosomal recessive disorder characterized by microcephaly, intellectual disability with absent speech, severe developmental delay, short stature, and hypotonia. Affected individuals also manifest aggressive behavior and have hearing loss.
Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies
An autosomal recessive neurodevelopmental and degenerative disorder characterized by primary microcephaly, profound global developmental delay, and severe intellectual disability. Additional clinical features include dysmorphic features, truncal hypotonia, peripheral spasticity, and lack of independent ambulation or speech acquisition. Brain imaging shows cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and delayed myelination.
Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures
An autosomal recessive disorder characterized by global developmental delay and impaired intellectual development apparent from infancy. Affected individuals have hypotonia, poor or absent motor skills, feeding difficulties with poor overall growth, microcephaly, mild dysmorphic features, and early-onset seizures. Additional variable features include nystagmus, cortical blindness, and spasticity.
Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay apparent in infancy, moderate to profound intellectual disability, poor or absent speech and language, delayed walking with variable gait abnormalities, and progressive microcephaly. Additional variable features include hypotonia, early-onset seizures, and a peripheral demyelinating or axonal peripheral sensorimotor neuropathy.
Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay apparent in infancy, delayed walking, ataxia, spasticity, impaired intellectual development with poor or absent speech and language, progressive microcephaly, and early-onset seizures in most patients. Facial dysmorphism and a demyelinating peripheral neuropathy may also be observed.
Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures
An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay, impaired intellectual development, microcephaly, early-onset seizures, and movement abnormalities.
Neurodevelopmental disorder with microcephaly, seizures, and brain atrophy
An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay, developmental regression with loss of milestones, severe microcephaly, and brain abnormalities, primarily cerebral atrophy and hypoplasia of the corpus callosum. Affected individuals develop seizures in the first year of life. Death in childhood may occur.
Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
An autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, intellectual disability, severe microcephaly, and cortical atrophy.
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis
An autosomal recessive disorder with onset at birth, characterized by severe global developmental delay, profoundly impaired intellectual development, progressive microcephaly, seizures, and transient neonatal cholestasis. Brain imaging shows agenesis or hypoplasia of the corpus callosum. Death in early childhood may occur.
Neurodevelopmental disorder with microcephaly, short stature, and speech delay
An autosomal recessive disorder characterized by global developmental delay, short stature, severely impaired intellectual development, microcephaly, poor or absent speech, and behavioral abnormalities including autistic features and aggressive behavior.
Neurodevelopmental disorder with midbrain and hindbrain malformations
An autosomal recessive neurodevelopmental disorder characterized by intellectual disability, speech delay, mild microcephaly, midbrain-hindbrain malformations, and variable dysmorphic features.
Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, speech delay, delayed walking, and behavioral abnormalities. Some patients develop spastic tetraplegia with inability to walk independently and never gain proper speech. Affected individuals may have variable additional features, including poor overall growth, hypotonia, tremor, ocular anomalies, seizures, and non-specific dysmorphic facial features.
Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features
An autosomal dominant neurodevelopmental disorder characterized by infantile-onset global developmental delay, severe to profound intellectual disability, mildly delayed walking with broad-based and unsteady gait, and absence of meaningful language. Patients have features of autism, with repetitive behaviors and poor communication, but usually are socially reactive and have a happy demeanor. More variable neurologic features include mild seizures, spasticity, and peripheral neuropathy.
Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties
An autosomal dominant disorder characterized by severe neonatal hypotonia, respiratory and feeding difficulties, encephalopathy, and severe developmental delay. Additional common features may include seizures, exaggerated startle reflex, abnormal movements, and dysmorphic facial features.
Neurodevelopmental disorder with neuromuscular and skeletal abnormalities
An autosomal recessive disorder characterized by developmental delay apparent from infancy or early childhood, intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity. Disease severity is highly variable. Most affected individuals have skeletal defects and dysmorphic facial features. Some may have ocular or auditory problems, behavioral abnormalities, and non-specific findings on brain imaging.
Neurodevelopmental disorder with non-specific brain abnormalities and with or without seizures
Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures
An autosomal dominant disorder characterized by developmental delay, intellectual disability, seizures, autism spectrum disorder, behavioral abnormalities, and variable non-specific brain malformations.
Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart
An autosomal dominant syndrome characterized by developmental delay, intellectual disability, brain anomalies, and neurological abnormalities including seizures, hypotonia, and behavioral problems such as autism spectrum disorders. Brain anomalies include abnormalities and/or thinning of the corpus callosum, diminished white matter volume, abnormal cerebellar vermis, and ventriculomegaly. Congenital defects of the eye, heart and genitourinary system are present in half of the patients.
Neurodevelopmental disorder with or without autism or seizures
An autosomal dominant disorder manifesting in infancy and characterized by global developmental delay, variably impaired intellectual development, and speech delay. Some patients have seizures, others have autistic features or behavioral abnormalities. Additional variable features include cardiac defects, failure to thrive, or brain imaging anomalies.
Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities
An early-onset neurodevelopmental disorder characterized by intellectual disability, motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and structural brain abnormalities including cerebral atrophy, cerebellar atrophy, and/or thin corpus callosum.
Neurodevelopmental disorder with or without early-onset generalized epilepsy
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, variably impaired intellectual development, speech delay, and behavioral abnormalities including autism or autistic features, attention deficits and hyperactivity, or aggressive behavior. About half of patients develop early-onset generalized epilepsy with different seizure types. The disease is apparent from infancy or early childhood.
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
An autosomal dominant neurodevelopmental disorder characterized by severe intellectual disability and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients.
Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive
An autosomal recessive neurodevelopmental disorder characterized by severe intellectual disability and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients.
Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy
Glycosylphosphatidylinositol biosynthesis defect 13
Intellectual developmental disorder, autosomal recessive 53
An autosomal recessive disorder characterized by delayed psychomotor development, hypotonia, and early-onset seizures in most patients. Additional variable features are cerebellar atrophy, ataxia, and non-specific dysmorphic features. Some patients may have the Emm-null blood group phenotype.
Neurodevelopmental disorder with or without seizures and gait abnormalities
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay apparent from infancy or early childhood, mild to profound intellectual disability, hypertonia early in life, which progresses to spasticity and impaired gait later, and behavioral abnormalities. Some patients may develop seizures of variable severity early in life.
Neurodevelopmental disorder with or without variable brain abnormalities
A disorder characterized by global developmental delay, impaired intellectual development, delayed walking, poor or absent speech, and variable brain anomalies including perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum.
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities
An autosomal dominant disorder characterized by motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Other variable features include autism spectrum disorder or autistic features and epilepsy.
Neurodevelopmental disorder with poor growth and skeletal anomalies
An autosomal recessive disorder characterized by global developmental delay and impaired intellectual development apparent from infancy. Affected individuals present with progressive microcephaly, hypotonia, delayed walking, poor or absent speech, intellectual disability, and variable skeletal anomalies. Variable features include seizures, non-specific dysmorphic facial features, oculomotor apraxia, and non-specific brain imaging abnormalities.
Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies
An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay, brain malformation, microcephaly, growth deficiency, and distinct facial dysmorphism. Disease severity is variable and death in infancy may occur.
Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss
An autosomal recessive disorder characterized by failure to thrive, severe developmental delay, intellectual disability, spastic tetraplegia with central hypotonia, chorea, hearing loss, micropenis and undescended testes, as well as mild elevation of liver enzymes.
Neurodevelopmental disorder with poor language and loss of hand skills
An autosomal dominant disorder characterized by psychomotor developmental stagnation or regression. NDPLHS manifest in the first years of life as loss of purposeful hand movements, loss of language, and intellectual disability.
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound intellectual disability and severely impaired or absent motor function. More variable features include seizures and optic atrophy.
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities
Microcephaly 15, primary, autosomal recessive
An autosomal recessive disorder characterized by impaired intellectual development with poor speech, progressive microcephaly, and appendicular spasticity. Brain imaging usually shows abnormalities, including enlarged ventricles, white matter defects, and atrophy or hypoplasia of brain tissue. Some patients have a more severe phenotype with seizures, lack of developmental milestones, and early death.
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
An autosomal recessive neurodevelopmental disorder characterized by developmental delay manifesting in infancy, inability to walk independently, mild to severe intellectual disability, poor overall growth, progressive microcephaly, and axial hypotonia. Additional variable features include brainstem and cerebellar involvement, seizures, joint contractures, ocular disturbances, episodic respiratory failure, and facial dysmorphism.
Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures
An autosomal dominant disorder characterized by global developmental delay or neurodevelopmental regression, hypotonia, progressive ataxia, intellectual disability, seizures, and abnormal movements.
Neurodevelopmental disorder with seizures and brain abnormalities
An autosomal recessive neurologic disorder characterized by global developmental delay and onset of seizures in the first months of life, and structural brain defects on brain imaging. Additional features may include pigmentary retinopathy with poor visual fixation and spasticity.
Neurodevelopmental disorder with seizures and brain atrophy
An autosomal recessive disorder characterized by brain atrophy, seizures, and developmental delay. Disease severity is variable. Severely affected individuals develop symptoms in utero, which may lead to spontaneous abortion. Patients at the mildest end of the phenotypic spectrum have onset of seizures later in childhood and show developmental delay with mildly impaired intellectual development and minimal brain atrophy.
Neurodevelopmental disorder with seizures and gingival overgrowth
An autosomal recessive disorder with variable clinical manifestations including delayed development, hypotonia, seizures, gingival hypertrophy associated with a prominent mandible or cherubism in the first years of life. Some patients have early normal development followed by developmental regression. Additional variable features are coarse facial features, optic atrophy, sensorineural hearing loss, and ataxia. Brain imaging may show cerebellar or cerebral atrophy and enlarged ventricles.
Neurodevelopmental disorder with seizures and non-epileptic hyperkinetic movements
Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements
An autosomal recessive, complex and progressive neurologic disorder characterized by severe neurodevelopmental delay and developmental regression, epileptic encephalopathy, postnatal microcephaly, hypotonia, and non-epileptic hyperkinetic movement disorder, including myoclonus dystonia, choreoathetosis, or generalized dyskinesia. Disease onset in infancy or first years of life.
Neurodevelopmental disorder with seizures and speech and walking impairment
An autosomal recessive disorder characterized by global developmental delay with intellectual disability and poor speech acquisition, and walking difficulties due to hypotonia, hypertonia, spasticity, or poor coordination. Additional features include seizures, mild dysmorphic features, and variable short stature.
Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, hypotonia, severe to profound intellectual disability, early-onset epilepsy, and microcephaly. Neuroimaging shows cerebral atrophy, thin corpus callosum and hypomyelination in a majority of cases. Death in childhood may occur.
Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities
An autosomal recessive disorder characterized by global developmental delay, severe to profound intellectual disability, progressive microcephaly, refractory early-onset epilepsy, white matter abnormalities, and periventricular calcifications.
Neurodevelopmental disorder with severe motor impairment and absent language
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, intellectual disability, severe speech impairment and gait abnormalities.
Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy
An autosomal recessive disorder with onset soon after birth or in early infancy. Affected individuals do not show developmental progress, are unable to sit or walk, do not acquire speech, have poor visual fixation, and show poor overall growth associated with feeding problems. Additional variable features include seizures, spasticity, and joint contractures. Brain imaging shows hypomyelination, thin corpus callosum, and cerebral and cerebellar atrophy.
Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties
An autosomal recessive disorder characterized by distinct craniofacial features, multisystem dysfunction, profound neurodevelopmental delays, and neonatal death.
Neurodevelopmental disorder with spastic diplegia and visual defects
An autosomal dominant disorder characterized by global developmental delay, severe intellectual disability with absent or very limited speech, microcephaly, spasticity, and visual abnormalities.
Neurodevelopmental disorder with spastic paraplegia and microcephaly
An autosomal recessive syndrome characterized by severe psychomotor developmental delay, dysarthria, walking difficulties, moderately to severely impaired intellectual development, poor or absent speech, and progressive microcephaly.
Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures
An autosomal recessive disorder characterized by profound developmental delay, progressive spastic quadriplegia and contractures, early-onset refractory epilepsy in most patients, and brain malformations. Neuroimaging shows ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter.
Neurodevelopmental disorder with spasticity and poor growth
An autosomal recessive disorder apparent soon after birth or in early infancy. NEDSG is characterized by axial hypotonia, delayed psychomotor development, poor feeding, failure to thrive, peripheral spasticity with hyperreflexia, poor overall growth, and microcephaly in most patients. Additional variable features include contractures, facial dysmorphisms, and ocular movement abnormalities.
Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, and poor or absent speech. More severely affected individuals do not achieve independent ambulation, whereas others develop some speech and can walk, or show regression later in childhood. Additional features include axial hypotonia, peripheral spasticity, dystonia, cataracts, and seizures. Brain imaging usually shows cerebellar hypoplasia, thin corpus callosum, cerebral atrophy, and hypomyelination.
Neurodevelopmental disorder with spasticity, hypomyelinating leukodystrophy, and brain abnormalities
Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
A severe autosomal recessive disorder characterized by global developmental delay with impaired intellectual development and poor or absent speech, axial hypotonia, and peripheral spasticity and hyperreflexia. Brain imaging shows hypomyelination with decreased white matter volume, cerebral and cerebellar atrophy, and thin corpus callosum. Polymicrogyria may be observed in rare cases. Some patients have a primary immunodeficiency or gastrointestinal disturbances similar to inflammatory bowel disease.
Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
An autosomal recessive disorder characterized by developmental delay apparent in infancy, impaired intellectual development with poor or absent speech, epilepsy, variable microcephaly, hypotonia, and spastic cerebral palsy. Brain abnormalities include simplified gyral pattern, defects of the operculum, and vermian hypoplasia. Death in early childhood may occur.
Neurodevelopmental disorder with speech delay and variable ocular anomalies
An autosomal recessive disorder characterized by global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism, and ophthalmological abnormalities. Brain imaging is usually normal, but abnormalities of the corpus callosum have been reported.
Neurodevelopmental disorder with speech impairment and dysmorphic facies
An autosomal dominant disorder characterized by global developmental delay, intellectual disability, speech delay, subtle facial dysmorphism, and behavioral and psychiatric problems.
Neurodevelopmental disorder with speech impairment and with or without seizures
An autosomal dominant disorder with variable manifestations. Severely affected individuals have profound global developmental delay, hypotonia, delayed or absent walking, absent speech, feeding difficulties, cortical visual impairment, and onset of hyperexcitability and seizures in the first months or years of life. Some patients manifest a milder phenotype characterized by mild to moderate cognitive impairment and mild speech delay, usually without seizures.
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, poor language, seizures, dysmorphic features, and thin corpus callosum.
Neurodevelopmental disorder with visual defects and brain anomalies
A disorder characterized by global developmental delay, speech delay, intellectual disability, structural brain abnormalities, and visual impairments including retinitis pigmentosa and optic atrophy.
Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures
An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals.
Neurodevelopmental disorder, non-progressive, with spasticity and transient opisthotonus
An autosomal recessive disorder characterized by delayed motor milestones, delayed walking, speech delay, axial hypotonia, and peripheral spasticity apparent from infancy or early childhood. Affected individuals often show transient opisthotonic posturing in infancy, and later show abnormal involuntary movements. Variably impaired intellectual development, and brain myelination defects are present in some patients.
Neurodevelopmental, jaw, eye, and digital syndrome
An autosomal dominant syndrome characterized by variable features including mild-to-severe developmental delay, speech delay, autistic and/or stereotypical behaviors, ocular anomalies, under- or overdeveloped jaw, and digital anomalies such as brachydactyly, clinodactyly, syndactyly, and contractures.
Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities
An autosomal dominant disorder characterized by dysmorphic craniofacial features, mild developmental delay, mildly impaired intellectual development or learning difficulties, speech delay, and behavioral abnormalities. About half of patients have congenital anomalies of the kidney and urinary tract and/or congenital cardiac defects, including septal defects.
Neurofacioskeletal syndrome with or without renal agenesis
Neurodevelopmental disorder with corpus callosum agenesis, craniofacial dysmorphism, and skeletal anomalies, with or without renal agenesis
An autosomal recessive syndrome characterized by developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, flexion contractures, brachydactyly of hands and feet with broad fingertips and toes, and dysmorphic features such as coarse face, upslanted palpebral fissures, broad nasal tip and wide mouth. Some patients manifest unilateral or bilateral renal agenesis.
A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors.
Genetic disorder characterized by bilateral vestibular schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas, and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management difficult, and patients suffer great morbidity and mortality.
Characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis.
Neurogenic scapuloperoneal syndrome Kaeser type
Autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy. A large clinical variability is observed ranging from scapuloperoneal, limb grindle and distal phenotypes with variable cardiac or respiratory involvement. Facial weakness, dysphagia and gynaecomastia are frequent additional symptoms. Affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Histological and immunohistochemical examination of muscle biopsy specimens reveal a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin.
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1
A progressive multisystem disease characterized by a variety of neurologic, endocrine, and, in some patients, pancreatic features. Variable clinical symptoms include global developmental delay, hypotonia, hearing loss, ataxia, hyporeflexia, facial dysmorphism, hypothyroidism, and pancreatic insufficiency.
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2
An autosomal recessive disorder with variable clinical manifestations and severity. Main features include cholestatic hepatitis, poor feeding, poor overall growth, and hypoglycemia apparent from infancy. Most patients have variable global developmental delay, sensorineural deafness, retinal abnormalities with visual defects, and hypotonia. Some patients have endocrine abnormalities. Brain imaging often shows dysmyelination, thin corpus callosum, cerebral atrophy, and white matter abnormalities. Death in early childhood may occur.
Neuromuscular disease and ocular or auditory anomalies with or without seizures
An autosomal dominant neuromuscular disorder characterized by variable features including myopathy, neuropathy, hypotonia, joint contractures, growth delay, chorioretinal lacunae, sensorineuronal deafness, agenesis of the corpus callosum, and seizures.
Neuromyotonia and axonal neuropathy, autosomal recessive
An autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves.
An autosomal dominant, slowly progressive, neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. Clinical manifestations are variable and include pyramidal and extrapyramidal symptoms, cerebellar ataxia, cognitive decline and dementia, peripheral neuropathy, and autonomic dysfunction.
Neuronopathy, distal hereditary motor, 10
Neuronopathy, distal hereditary motor, type X
A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. HMN10 is an autosomal dominant form characterized by length-dependent motor neuropathy primarily affecting the lower limbs, and onset of distal muscle weakness and atrophy in early childhood resulting in walking difficulties and gait abnormalities. Some affected individuals have pyramidal signs, including hyperreflexia. More variable features may include mild intellectual disability, minor gyration defects on brain imaging, foot deformities, and connective tissue defects.
Neuronopathy, distal hereditary motor, 2A
Distal hereditary motor neuropathy type IIA
Spinal muscular atrophy distal adult autosomal dominant IIA
A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.
Neuronopathy, distal hereditary motor, 2B
Distal hereditary motor neuropathy type IIB
Neuronopathy, distal hereditary motor, 2C
Distal hereditary motor neuropathy type IIC
Neuronopathy, distal hereditary motor, 2D
Autosomal dominant spinal muscular atrophy distal calf-predominant
Distal hereditary motor neuropathy type IID
A disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles. Some patients may lose independent ambulation later in the disease course. Sensory impairment is typically not present, and cognition and bulbar function are normal.
Neuronopathy, distal hereditary motor, 5A
Distal hereditary motor neuronopathy type VA
Distal hereditary motor neuropathy type V
Distal hereditary motor neuropathy type VA
Spinal muscular atrophy distal with upper limb predominance
A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.
Neuronopathy, distal hereditary motor, 5B
Distal hereditary motor neuropathy type VB
A disorder characterized by distal muscular atrophy mainly affecting the upper extremities, in contrast to other distal motor neuronopathies. These constitute a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN5B is characterized by onset in the first or second decade of distal muscle weakness and atrophy, primarily affecting the intrinsic hand muscles, but also affecting the lower legs, resulting in abnormal gait and pes cavus.
Neuronopathy, distal hereditary motor, 5C
Distal hereditary motor neuronopathy type VC
Neuronopathy, distal hereditary motor, type VC
Spinal muscular atrophy, distal, type 5C
Spinal muscular atrophy, distal, type VC
A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. HMN5C is characterized by distal muscular atrophy primarily affecting the upper limbs. Lower limb involvement may occur at the same time or later. Clinical features are highly variable even within families, and include poor fine hand motor skills, difficulty walking, foot deformities, spasticity and hyperreflexia. Some HMN5C patients show axonal peripheral neuropathy and distal sensory impairment. HMN5C inheritance is autosomal dominant with incomplete penetrance.
Neuronopathy, distal hereditary motor, 6
Distal hereditary motor neuropathy type VI
Severe infantile axonal neuronopathy with respiratory failure
Severe infantile axonal neuropathy with respiratory failure
Spinal muscular atrophy distal autosomal recessive 1
Spinal muscular atrophy with respiratory distress 1
Neuronopathy, distal hereditary motor, 7A
Distal hereditary motor neuronopathy type VIIA
Distal hereditary motor neuropathy type VIIA
Distal hereditary motor neuropathy with vocal cord paralysis
Distal spinal muscular atrophy with vocal cord paralysis
A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN7A is characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve.
Neuronopathy, distal hereditary motor, 7B
Distal hereditary motor neuropathy type VIIB
Distal hereditary motor neuropathy with vocal cord paralysis type VIIB
Lower motor neuron disease dynactin type
Neuronopathy, distal hereditary motor, 8
Distal spinal muscular atrophy, congenital non-progressive
Neuropathy, distal hereditary motor, type VIII
Spinal muscular atrophy congenital benign with contractures
A clinically variable, neuromuscular disorder characterized by congenital lower motor neuron disorder restricted to the lower part of the body. Clinical manifestations include non-progressive muscular atrophy, thigh muscle atrophy, weak thigh adductors, weak knee and foot extensors, minimal jaw muscle and neck flexor weakness, flexion contractures of knees and pes equinovarus. Tendon reflexes are normal.
Neuronopathy, distal hereditary motor, 9
Neuronopathy, distal hereditary motor, type IX
Neuropathy, distal hereditary motor, type IX
An autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both the lower and upper limbs.
An autosomal dominant syndrome characterized by developmental delay, impaired intellectual development, and variable eye abnormalities including anophthalmia, microphthalmia, and coloboma. Other common systemic features include congenital heart and kidney defects, hypotonia, failure to thrive, and microcephaly.
An autosomal dominant multisystem disorder characterized by significant neurological impairment with structural brain defects and seizures, poor feeding, poor postnatal growth, ocular anomalies, dysmorphic facial features, and variable skeletal, cardiac and genitourinary defects. Death in infancy may occur.
Neuropathy, ataxia, and retinitis pigmentosa
Neurogenic muscle weakness, ataxia, and retinitis pigmentosa
A syndrome characterized by variable combination of developmental delay, psychomotor retardation, hearing loss, optic atrophy and retinitis pigmentosa, dementia, seizures, ataxia, proximal neurogenic muscle weakness, and sensory neuropathy.
Neuropathy, congenital hypomyelinating, 1, autosomal recessive
Congenital hypomyelinating neuropathy autosomal recessive
Neuropathy, congenital hypomyelinating or amyelinating
A severe degenerating neuropathy that results from a congenital impairment in myelin formation. It is clinically characterized by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (as low as 3m/s). Some patients manifest nearly complete absence of spontaneous limb movements, respiratory distress at birth, and complete absence of myelin shown by electron microscopy of peripheral nerves.
Neuropathy, congenital hypomyelinating, 2
Hypomyelinating neuropathy, congenital, 2
A form of congenital hypomyelinating neuropathy, a neurologic disorder characterized by early-onset hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (NCV) resulting from improper myelination of axons. In its extreme form, it may present with severe joint contractures or arthrogryposis multiplex congenita and respiratory insufficiency. In less severe cases patients may achieve walking. Patients lack both active myelin breakdown and well-organized onion bulbs on sural nerve biopsies, have absence of inflammation, and show hypomyelination of most or all fibers. CHN2 inheritance is autosomal dominant.
Neuropathy, congenital hypomyelinating, 3
A form of congenital hypomyelinating neuropathy, a neurologic disorder characterized by early-onset hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (NCV) resulting from improper myelination of axons. In its extreme form, it may present with severe joint contractures or arthrogryposis multiplex congenita and respiratory insufficiency. In less severe cases patients may achieve walking. Patients lack both active myelin breakdown and well-organized onion bulbs on sural nerve biopsies, have absence of inflammation, and show hypomyelination of most or all fibers. CHN3 is a severe autosomal recessive form characterized by onset of neurogenic muscle impairment in utero. Affected individuals have profoundly impaired psychomotor development and may die in infancy or early childhood.
Neuropathy, hereditary motor and sensory, 6A, with optic atrophy
Hereditary motor and sensory neuropathy type VI
Hereditary motor and sensory neuropathy type VIA
An autosomal dominant neurologic disorder characterized by optic atrophy and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities.
Neuropathy, hereditary motor and sensory, 6B, with optic atrophy
Hereditary motor and sensory neuropathy type VIB
Neuropathy, hereditary motor and sensory, type VIB
An autosomal recessive neurologic disorder characterized by early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities.
Neuropathy, hereditary motor and sensory, 6C, with optic atrophy
Hereditary motor and sensory neuropathy type VIC
Neuropathy, hereditary motor and sensory, type VIC
Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy
An autosomal recessive neurologic disorder characterized by childhood onset of axonal, sensorimotor polyneuropathy affecting mainly the lower limbs, and adult-onset optic atrophy. Clinical features include progressive distal muscle weakness and atrophy, significant standing and walking difficulties, areflexia, neurogenic pain and progressive visual impairment.
Neuropathy, hereditary motor and sensory, Okinawa type
Hereditary motor and sensory neuropathy, proximal type
Hereditary motor and sensory neuropathy Okinawa
A neurodegenerative disorder characterized by young adult onset of proximal muscle weakness and atrophy, muscle cramps, and fasciculations, with later onset of distal sensory impairment. The disorder is slowly progressive and clinically resembles amyotrophic lateral sclerosis.
Neuropathy, hereditary motor and sensory, Russe type
Charcot-Marie-Tooth disease autosomal recessive type 4G
An autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.
Neuropathy, hereditary motor, with myopathic features
An autosomal recessive, neuromyopathic disorder that manifests in childhood or adulthood with proximal and distal muscle weakness predominantly of the lower limbs. Affected individuals have difficulty climbing stairs and problems standing on the heels. Most patients have foot deformities, and some may have leg muscle atrophy. Muscle biopsy and electrophysiologic studies are consistent with both a myopathic process and an axonal motor neuropathy.
Neuropathy, hereditary sensory and autonomic, 1A
Hereditary sensory radicular neuropathy autosomal dominant type 1A
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1A is an autosomal dominant axonal form with onset in the second or third decades. Initial symptoms are loss of pain, touch, heat, and cold sensation over the feet, followed by distal muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers and distal amputations.
Neuropathy, hereditary sensory and autonomic, 1C
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1C symptoms include loss of touch and vibration in the feet, dysesthesia and severe panmodal sensory loss in the upper and lower limbs, distal lower limb sensory loss with ulceration and osteomyelitis, and distal muscle weakness.
Neuropathy, hereditary sensory and autonomic, 2A
Hereditary sensory and autonomic neuropathy type IIA
Hereditary sensory radicular neuropathy autosomal recessive
Progressive sensory neuropathy of children
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves.
Neuropathy, hereditary sensory and autonomic, 2B
Hereditary sensory and autonomic neuropathy type IIB
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2B is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation. Onset occurs in the first or second decade, with impaired nociception and progressive mutilating ulceration of the hands and feet with osteomyelitis and acroosteolysis. Amputations of the hands and feet are common. Autonomic dysfunction includes hyperhidrosis, urinary incontinence, and slow pupillary light response.
Neuropathy, hereditary sensory and autonomic, 3
Hereditary sensory and autonomic neuropathy type III
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN3 patients manifest a variety of symptoms such as alacrima, decreased taste, decreased sensitivity to pain and temperature, vasomotor instability, hypoactive or absent deep tendon reflexes, vomiting crises, and gastrointestinal dysfunction.
Neuropathy, hereditary sensory and autonomic, 5
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable.
Neuropathy, hereditary sensory and autonomic, 6
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN6 is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection.
Neuropathy, hereditary sensory and autonomic, 7
Congenital insensitivity to pain with gastrointestinal dysfunction and hyperhidrosis
Hereditary sensory and autonomic neuropathy type VII
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN7 is characterized by congenital inability to experience pain resulting in self-mutilations, slow-healing wounds, and multiple painless fractures. mild muscle weakness, delayed motor development, slightly reduced motor and sensory nerve conduction velocities, hyperhidrosis and gastrointestinal dysfunction.
Neuropathy, hereditary sensory and autonomic, 8
Hereditary sensory and autonomic neuropathy type VIII
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN8 patients manifest congenital insensitivity to pain resulting in ulceration to the fingers, tongue, lips, and other distal appendages. Some patients may also have decreased sweating and tear production.
Neuropathy, hereditary sensory and autonomic, 9, with developmental delay
Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay
Spastic paraplegia 49, autosomal recessive
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN9 is characterized by global developmental delay and intellectual disability, axial and appendicular hypotonia, dysarthria, and an abnormal gait that is often described as ataxic. Other features may include peripheral neuropathy, hyporeflexia, and autonomic dysfunction. Affected individuals also have dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, which may be fatal.
A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement.
Neuropathy hereditary sensory with hearing loss and dementia
A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.
An autosomal dominant sensory neuropathy affecting the lower limbs. Distal sensory impairment becomes apparent during the second or third decade of life, resulting in painless ulceration of the feet with poor healing, which can progress to osteomyelitis, bone destruction, and amputation. There is no autonomic involvement, spasticity, or cognitive impairment.
A neurodegenerative disorder characterized by onset in the first decade of progressive distal sensory loss leading to ulceration and amputation of the fingers and toes. Affected individuals also develop distal muscle weakness, primarily affecting the lower limbs.
Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessive
A disease characterized by spastic paraplegia and progressive distal sensory neuropathy leading to mutilating ulcerations of the upper and lower limbs.
Neutral lipid storage disease with myopathy
Neutral lipid storage disease without ichthyosis
Neutral lipid storage disorder (NLSD) with myopathy but without ichthyosis. NLSDs are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Individuals with NLSDM did not show obesity, in spite of a defect in triglyceride degradation in fibroblasts and in marked triglyceride storage in liver, muscles, and other visceral cells.
Neutropenia, severe congenital 1, autosomal dominant
A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Neutropenia, severe congenital 2, autosomal dominant
Neutropenia, severe congenital 3, autosomal recessive
A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. Some patients affected by severe congenital neutropenia type 3 have neurological manifestations such as psychomotor retardation and seizures.
Neutropenia, severe congenital 4, autosomal recessive
Neutropenia, severe congenital 5, autosomal recessive
An autosomal recessive primary immunodeficiency disorder characterized primarily by neutropenia and neutrophil dysfunction, a lack of response to G-CSF, life-threatening infections, bone marrow fibrosis, and renal extramedullary hematopoiesis.
Neutropenia, severe congenital 6, autosomal recessive
Neutropenia, severe congenital 7, autosomal recessive
A form of severe congenital neutropenia, a disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Neutropenia, severe congenital 8, autosomal dominant
Neutropenia, severe congenital 9, autosomal dominant
A form of severe congenital neutropenia, a disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. SCN9 is characterized by onset of neutropenia in the first years of life. Rare patients may exhibit additional features such as seizures, learning difficulties, or cataracts. Patients with SCN9 do not have 3-methylglutaconic aciduria.
Neutropenia, severe congenital, X-linked
A rare type of epidermal nevus characterized by closely arranged, dilated, plugged follicular ostia in a honeycomb pattern. The plugged ostia contain lamellated keratinaceous material, and their appearance resembles black dots. NC may be non-pyogenic with an acne-like appearance or associated with the formation of cysts, papules, pustules, and abscesses. Most commonly it affects the face and neck area and, by exception, other anatomical regions, including genital area, palms, and soles. NC lesions might present with various patterns of distribution: unilateral, bilateral, linear, interrupted, segmental, or blaschkoid.
A congenital hyperpigmented patch, which progressively evolves, developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanoma.
A rare disorder characterized by severe intellectual disability with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, prominent finger joints and broad distal phalanges. Some of the features are progressive with time.
Niemann-Pick disease acute neuronopathic form
Niemann-Pick disease acute neurovisceral form
Niemann-Pick disease classical infantile form
Niemann-Pick disease intermediate protracted neurovisceral
An early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, intellectual disability, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B.
Niemann-Pick disease adult non-neuronopathic form
Niemann-Pick disease intermediate with visceral involvement and rapid progression
A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood.
Neurovisceral storage disease with vertical supranuclear ophthalmoplegia
Niemann-Pick disease chronic neuronopathic form
Niemann-Pick disease subacute juvenile form
Niemann-Pick disease with cholesterol esterification block
Niemann-Pick disease without sphingomyelinase deficiency
A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C1 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. An allelic variant of Niemann-Pick disease type C1 is found in people with Nova Scotia ancestry. Patients with the Nova Scotian clinical variant are less severely affected.
A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C2 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood.
Night blindness, congenital stationary, 1A
Congenital stationary night blindness with myopia
X-linked congenital stationary night blindness
A non-progressive retinal disorder characterized by impaired night vision. Congenital stationary night blindness type 1A is characterized by impaired scotopic vision, myopia, hyperopia, nystagmus and reduced visual acuity.
Night blindness, congenital stationary, 1B
Complete congenital stationary night blindness autosomal recessive
A non-progressive retinal disorder characterized by impaired night vision. Congenital stationary night blindness type 1B is an autosomal recessive form associated with a negative electroretinogram waveform. Patients are night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system. ERGs in response to single brief flashes of light have clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicate a markedly reduced on response and a nearly normal OFF response. There is no subjective delay in the perception of suddenly appearing white vs black objects on a gray background.
Night blindness, congenital stationary, 1C
A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia.
Night blindness, congenital stationary, 1D
An autosomal recessive form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision. CSNB1D is characterized by a Riggs type of electroretinogram (proportionally reduced a- and b-waves). Patients have visual acuity within the normal range and no symptoms of myopia and/or nystagmus.
Night blindness, congenital stationary, 1E
An autosomal recessive, non-progressive retinal disorder characterized by impaired night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. Affected individuals have an ERG waveform that lacks the b-wave because of failure to transmit the photoreceptor signal through the retinal depolarizing bipolar cells.
Night blindness, congenital stationary, 1F
Complete congenital stationary night blindness 1F autosomal recessive
An autosomal recessive form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia.
Night blindness, congenital stationary, 1G
An autosomal recessive form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision or in dim light, with good vision only on bright days.
Night blindness, congenital stationary, 1H
A form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision or in dim light, with good vision only on bright days. CSNB1H patients present with childhood-onset night blindness and middle age-onset photophobia, but have near-normal vision and do not exhibit nystagmus or high myopia. CSNB1H inheritance is autosomal recessive.
Night blindness, congenital stationary, 1I
A form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision or in dim light, with good vision only on bright days. CSNB1I patients present with night blindness from infancy or early childhood. Visual acuity is preserved, but some patients have color vision and/or visual field defects. Progression to mild retinitis pigmentosa may occur. CSNB1I inheritance is autosomal recessive.
Night blindness, congenital stationary, 2A
Congenital stationary night blindness type 2
Night blindness, congenital stationary, autosomal dominant 1
Rhodopsin-related congenital stationary night blindness
Night blindness, congenital stationary, autosomal dominant 2
Congenital stationary night blindness Rambusch type
Night blindness, congenital stationary, autosomal dominant 3
Congenital stationary night blindness Nougaret type
Night blindness, congenital stationary, Oguchi type 1
A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is an autosomal recessive form associated with fundus discoloration and abnormally slow dark adaptation.
Night blindness, congenital stationary, Oguchi type 2
A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is associated with fundus discoloration and abnormally slow dark adaptation.
A disorder characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, immunodeficiency and predisposition to cancer, particularly to lymphoid malignancies.
Nijmegen breakage syndrome-like disorder
Microcephaly and spontaneous chromosome instability without immunodeficiency
A disorder similar to Nijmegen breakage syndrome and characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, short stature and bird-like face. Immunodeficiency is absent.
Chondrodysplasia-pseudohermaphroditism syndrome
An autosomal recessive syndrome characterized by progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Additional variable features include early infantile-onset seizures, intrauterine and postnatal growth retardation, generalized chondrodysplasia, and micromelia. 46,XY gonadal dysgenesis may be present.
An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, global developmental delay, speech impairment, and behavioral abnormalities including autism spectrum disorder and aggressive behavior. Other features include a thin corpus callosum, and mild facial dysmorphism. Disease onset is in infancy or early childhood.
A condition characterized by accumulation of triglycerides in the liver. It is associated with adverse metabolic consequences, including insulin resistance and dyslipidemia. In a subset of individuals, hepatic steatosis promotes an inflammatory response in the liver, referred to as steatohepatitis, which can progress to cirrhosis and liver cancer. NAFLD is the most common form of liver disease in Western countries.
Non-arteritic anterior ischemic optic neuropathy
An ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.
Autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms.
Non-phenylketonuria hyperphenylalaninemia
Mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.
Non-syndromic cleft lip with or without cleft palate 10
A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
Non-syndromic cleft lip with or without cleft palate 11
A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. OFC15 inheritance is autosomal dominant.
Non-syndromic cleft lip with or without cleft palate 5
Non-syndromic cleft lip with or without cleft palate 6
Non-syndromic cleft lip with or without cleft palate 7
Inclusion body myopathy, hereditary, autosomal recessive
Inclusion body myopathy, quadriceps-sparing
Inclusion body myopathy 2, autosomal recessive
Myopathy, distal, with or without rimmed vacuoles
Autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens.
Noonan-like/multiple giant cell lesion syndrome
Noonan syndrome-like disorder with multiple giant cell lesions
Noonan syndrome with pigmented villonodular synovitis
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS10 inheritance is autosomal dominant.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS11 inheritance is autosomal dominant.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS12 inheritance is autosomal dominant. There is considerable variability in severity.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. NS14 inheritance is autosomal recessive.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS2 inheritance is autosomal recessive.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. Some patients with NS4 have polyarticular villonodular synovitis.
Noonan syndrome-like disorder with loose anagen hair 1
A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair.
Noonan syndrome-like disorder with loose anagen hair 2
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia.
Recessive disorder characterized by very early childhood blindness due to degenerative and proliferative changes of the neuroretina. Approximately 50% of patients show some form of progressive mental disorder, often with psychotic features, and about one-third of patients develop sensorineural deafness in the second decade. In addition, some patients have more complex phenotypes, including growth failure and seizure.
North American Indian childhood cirrhosis
Severe autosomal recessive intrahepatic cholestasis, originally described in Ojibway-Cree children from northwestern Quebec. NAIC typically presents with transient neonatal jaundice, in a child who is otherwise healthy, and progresses to biliary cirrhosis and portal hypertension. Biochemical and histopathological features suggest involvement of the bile ducts rather than of the bile canaliculi. They include elevated gamma glutamyltransferase and alkaline phosphatase levels, and, typically, marked fibrosis around bile ducts. Clinically, NAIC is distinct from other nonsyndromic familial cholestases because of its marked cholangiopathic features and severe degree of fibrosis on liver histology.
Nystagmus infantile periodic alternating X-linked
A condition defined as conjugated, spontaneous and involuntary ocular oscillations that appear at birth or during the first three months of life. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding.
A neurodevelopmental disorder characterized by global developmental delay, speech delay, intellectual disability and a subtle facial gestalt. Additional common features include autism, seizures, hypotonia and functional gastrointestinal abnormalities.
A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.
An autosomal dominant disorder characterized by early-onset obesity, overgrowth, hyperinsulinemia, and hypopigmentation of the skin. Some affected individuals experience hyperphagia and exhibit reduced energy expenditure.
Obesity, early-onset, with adrenal insufficiency and red hair
An autosomal recessive disorder characterized by early-onset obesity due to severe hyperphagia, pigmentary abnormalities, mainly pale skin and red hair, and secondary hypocortisolism.
Obesity, hyperphagia, and developmental delay
A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language.
Ehlers-Danlos syndrome occipital horn type
An X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities include occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga.
An inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. It is typically characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina.
Schorderet-Munier-Franceschetti syndrome
A syndrome characterized by microphthalmia, microcornea, anterior segment dysgenesis, cataract, ocular coloboma, retinal pigment epithelium abnormalities, rod-cone dystrophy, and anomalies of the external ear.
A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances.
Oculodentodigital dysplasia, autosomal recessive
Autosomal recessive oculodentoosseous dysplasia
Aplasia cutis congenita with epibulbar dermoids
A syndrome characterized by the association of epibulbar dermoids and aplasia cutis congenita. Affected individuals show multiple, asymmetric, atrophic, non-scarring and hairless regions that may be associated with hamartomas. Ectodermal changes include linear hyperpigmentation that may follow the lines of Blaschko and rarely epidermal nevus-like lesions. Epibulbar dermoids may be uni-or bilateral. Additional ocular anomalies such as skin tags of the upper eyelid, rarely optic nerve or retinal changes, and microphthalmia can be present. The phenotypic expression is highly variable, and various other abnormalities have occasionally been reported including growth failure, lymphedema, cardiovascular defects, as well as neurodevelopmental symptoms like developmental delay, epilepsy, learning difficulties, and behavioral abnormalities. Benign tumor-like lesions such as nonossifying fibromas of the long bones and giant cell granulomas of the jaws have repeatedly been observed and appear to be age-dependent, becoming a common manifestation in individuals aged 5 years or older.
Oculogastrointestinal neurodevelopmental syndrome
An autosomal recessive neurodevelopmental disorder characterized by growth deficits, microcephaly, global developmental delay, hearing loss, and microphthalmia and/or coloboma. Other congenital anomalies include imperforate anus, horseshoe kidney, and structural cardiac defects. Some patients have been reported with normal motor and cognitive development.
An autosomal recessive disorder characterized by ptosis and elevation of the eyelid on ipsilateral abduction. OCABSN features are consistent with abnormal innervation of the levator palpebrae superioris muscle, which raises the eyelid, and the lateral rectus muscle, which controls lateral eye movement.
A form of late-onset slowly progressive myopathy characterized by eyelid ptosis, dysphagia and, sometimes by other cranial and limb-muscle involvement.
Faciooculolaryngopharyngeal myopathy with distal and respiratory involvement
A form of oculopharyngodistal myopathy, a muscle disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles in the muscle fibers and myopathic changes of differing severity. OPDM1 inheritance pattern is autosomal dominant.
A form of oculopharyngodistal myopathy, a muscle disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles in the muscle fibers and myopathic changes of differing severity. OPDM2 inheritance pattern is autosomal dominant.
A form of oculopharyngodistal myopathy, a rare hereditary muscle disease characterized by progressive distal limb weakness, ptosis, ophthalmoplegia, bulbar muscle weakness and rimmed vacuoles on muscle biopsy. In addition to muscular features, OPDM3 patients may develop pigmentary retinopathy, peripheral neuropathy, or hearing loss. Cognition is usually not affected, but there may be deficits or psychiatric manifestations. Brain imaging tends to show a leukoencephalopathy, often with a characteristic linear signal along the corticomedullary junction on brain imaging. OPDM3 is a slowly progressive form with an autosomal dominant transmission pattern, and variable age at onset ranging from childhood to late adulthood.
A form of oculopharyngodistal myopathy, a muscle disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles in the muscle fibers and myopathic changes of differing severity. OPDM4 is an autosomal dominant form characterized by slow progression and onset of symptoms in the second or third decades.
Cataracts, early-onset, with skeletal and dental anomalies
An autosomal recessive syndrome characterized by congenital cataracts, short stature, dysmorphic features with coarse facies, dental anomalies, multiple skeletal abnormalities, and neurological manifestations. Other recurrent features include hearing loss, secondary glaucoma, and nephrocalcinosis.
Ectodermal dysplasia 16, hypo- or hyperhidrotic/hair/tooth/nail type
A rare autosomal recessive ectodermal dysplasia characterized by dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin.
Spondylometaphyseal dysplasia with dentinogenesis imperfecta
An autosomal recessive disorder of skeletal and dental development characterized by mesomelic shortening of tubular bones, ligamentous laxity, scoliosis, and dentinogenesis imperfecta involving both primary and secondary dentition. Radiologic features include trident pelvis, posteriorly flattened vertebrae, and brachydactyly with cone-shaped epiphyses.
Odontochondrodysplasia 2 with hearing loss and diabetes
An autosomal recessive disorder characterized by dentinogenesis imperfecta, delayed tooth eruption, growth retardation with proportionate short stature, skeletal abnormalities, and dysmorphic facies in association with insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability.
Say-Barber-Biesecker variant of Ohdo syndrome
Say-Barber-Biesecker-Young-Simpson syndrome
A syndrome characterized by distinctive facial appearance with severe blepharophimosis, an immobile mask-like face, a bulbous nasal tip, and a small mouth with a thin upper lip. The condition presents in infancy with severe hypotonia and feeding problems. Associated skeletal problems include joint laxity, abnormally long thumbs and great toes, and dislocated or hypoplastic patellae. Structural cardiac defects are present in around 50% of cases, and dental anomalies, including small and pointed teeth, are common. Optic atrophy and conductive or sensorineural deafness are repeatedly reported. Many affected individuals have abnormalities of thyroid structure or function. SBBYSS is usually associated with severe intellectual disability, delayed motor milestones, and significantly impaired speech.
A syndrome characterized by intellectual disability, feeding problems, and distinctive facial appearance with coarse facial features, severe blepharophimosis, ptosis, a bulbous nose, micrognathia and a small mouth. Dental hypoplasia and deafness can be considered as common manifestations of the syndrome. Male patients show cryptorchidism and scrotal hypoplasia.
An autosomal dominant neurodevelopmental disorder characterized by developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and variable dysmorphic features.
Affected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types.
Congenital trichomegaly, pigmentary retinal degeneration, and short stature
Trichomegaly, retina pigmentary degeneration, dwarfism
Trichomegaly retina pigmentary degeneration dwarfism
A rare autosomal recessive, congenital syndrome characterized by trichomegaly, severe chorioretinal atrophy and multiple pituitary hormone deficiencies. It results in intellectual impairment and dwarfism, if untreated. Clinical features include hypogonadotropic hypogonadism during puberty, pigmentary retinal degeneration, ataxia, spastic paraplegia, and peripheral neuropathy.
Mutilating palmoplantar keratoderma with periorificial keratotic plaques
An autosomal dominant, rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes.
Palmoplantar keratoderma, mutilating, with periorificial keratotic plaques 2
A form of Olmsted syndrome, a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes. OLMS2 is an autosomal dominant form with onset in the first months of life or in early childhood.
Mutilating palmoplantar keratoderma with periorificial keratotic plaques, X-linked
A rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes.
Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.
Micromelic dysplasia congenital with dislocation of radius
A rare autosomal recessive skeletal dysplasia characterized by facial dysmorphism and severe congenital micromelia with shortening and distal tapering of the humeri and femora, to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin.
A rare autosomal dominant skeletal dysplasia characterized by short humeri, radial head dislocation, short first metacarpals, facial dysmorphism and genitourinary anomalies.
Omphalocele due to duplication of 1p31.3
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. It appears as a skin-covered protrusion at the umbilicus during crying, coughing, or straining.
Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome
Glycosylphosphatidylinositol biosynthesis defect 24
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, seizures or tonic posturing, dysmorphic facial features, and hypoplastic terminal phalanges and nails.
An infertility disorder caused by defective oocyte maturation that results in abnormal eggs lacking a zona pellucida. Affected females have normal menstrual cycles and sex hormone levels, no obstruction in the fallopian tubes or abnormalities of the uterus or adnexa.
An autosomal recessive infertility disorder due to abnormal fertilization of mature oocytes, with development of multiple pronuclei or absent pronucleus, and early embryonic arrest.
An autosomal recessive disorder characterized by decreased or absent fertility and poor embryonic outcomes with assisted reproductive technology.
An autosomal recessive disorder characterized by infertility due to early embryonic arrest.
An autosomal recessive female infertility disorder characterized by embryonic development arrest and embryo implantation failure.
A primary infertility disorder caused by defective oocyte maturation. Oocytes are arrested at metaphase I, and have an abnormal or no detectable spindle on polarization microscopy. OOMD2 inheritance can be autosomal dominant or autosomal recessive.
An autosomal dominant infertility disorder characterized by abnormal oocytes that lack the zona pellucida, and oocytes degeneration.
An infertility disorder characterized by oocyte maturation arrest that can occur at different stages of maturation. Some oocytes exhibit maturation arrest at the germinal vesicle stage and others at the metaphase I stage. Oocytes progressing to polar body I either undergo fertilization failure or, in those that are fertilized, early embryonic arrest.
An autosomal recessive infertility disorder characterized by oocyte inability to exit metaphase II, resulting in fertilization failure.
An autosomal recessive infertility disorder characterized by oocyte fertilization failure, due to defective sperm-binding to an abnormally thin zona pellucida in patient oocytes.
An autosomal dominant infertility disorder due to oocyte degeneration and death, which may occur before or after fertilization.
An autosomal recessive infertility disorder due to failure of the fertilized ovum to undergo zygotic cleavage.
An autosomal recessive infertility disorder due to oocyte meiotic arrest at metaphase I. Abnormal zygotic cleavage has been observed in some patients.
A rare disorder presenting with ocular anomalies, ranging from mild microphthalmia to true anophthalmia, and limb anomalies. Limb malformations include fused 4th and 5th metacarpals and short 5th finger in hands, and oligodactyly in foot (four toes). Most patients have bilateral anophthalmia/ microphthalmia, but unilateral abnormality is also noted. Other malformations are rare, but venous or vertebral anomaly was recognized each in single cases.
Ophthalmoplegia, external, with rib and vertebral anomalies
An autosomal recessive disorder characterized by congenital nonprogressive external ophthalmoplegia, ptosis, scoliosis, torticollis, and vertebral and rib anomalies.
Hypertelorism with esophageal abnormality and hypospadias
A congenital midline malformation syndrome characterized by hypertelorism, genital-urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects.
X-linked disorder characterized by intellectual disability, relative macrocephaly, hypotonia and constipation.
A rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with very delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges.
A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA1 is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disk pallor, color vision deficits, and centrocecal scotoma of variable density.
Optic atrophy 10 with or without ataxia, impaired intellectual development, and seizures
An autosomal recessive disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA10 patients may also manifest mild ataxia, mild intellectual disability and, rarely, generalized seizures.
An autosomal recessive disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA11 patients also manifest delayed psychomotor development, intellectual disability, ataxia, and leukoencephalopathy on brain imaging.
An autosomal dominant disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA12 patients manifest slowly progressive visual impairment with onset usually in the first decade. Some patients may exhibit additional features including impaired intellectual development, dystonia, movement disorders, or ataxia.
Optic atrophy 13 with retinal and foveal abnormalities
An autosomal dominant disease characterized by visual impairment in association with bilateral optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. Many OPA13 patients also exhibit retinal pigmentary defects, attenuated retinal vasculature, macular dystrophy, and foveopathy. Some patients may develop additional systemic features, including sensorineural deafness and progressive nephropathy resulting in renal failure.
Autosomal dominant optic atrophy and cataract
A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA3 is associated with cataract and a neurologic disorder characterized by extrapyramidal signs and ataxia.
A form of optic atrophy, a disease characterized by progressive visual loss in association with a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA5 is an autosomal dominant non-syndromic form that manifests as slowly progressive visual loss with variable onset from the first to third decades. Additional ocular abnormalities may include central scotoma and dyschromatopsia.
Optic atrophy 7 with or without auditory neuropathy
A hereditary condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA7 is an autosomal recessive juvenile-onset optic atrophy characterized by severe bilateral deficiency in visual acuity, optic disk pallor, and central scotoma. Some patients manifest hearing loss.
A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.
Optic disk anomalies with retinal and/or macular dystrophy
An ocular disorder characterized by optic nerve dysplasia, optic disk anomalies, chorioretinal dystrophy and macular atrophy. Some patients have microphthalmia.
Ornithine carbamoyltransferase deficiency
Hyperammonemia due to ornithine carbamoyltransferase deficiency
An X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms.
Cleft lip with or without cleft palate, nonsyndromic, 8
Non-syndromic cleft lip with or without cleft palate 8
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD1 is X-linked dominant syndrome, lethal in males. Craniofacial findings consist of facial asymmetry, hypertelorism, median cleft, or pseudocleft of the upper lip, hypoplasia of the alae nasi, oral clefts and abnormal frenulea, tongue anomalies (clefting, cysts, hamartoma), and anomalous dentition involving missing or extra teeth. Asymmetric brachydactyly and/or syndactyly of the fingers and toes occur frequently. Approximately 50% of OFD1 females have some degree of intellectual disability. Some patients have structural central nervous system anomalies such as agenesis of the corpus callosum, cerebellar agenesis, or a Dandy-Walker malformation. Patients with OFD1 can develop fibrocystic disease of the liver and pancreas, in addition to polycystic kidneys.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD14 patients show severe microcephaly, cerebral malformations the molar tooth sign, and intellectual disability in addition to canonical OFDS features.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD15 features include facial dysmorphism, lobulated tongue, clefting of the alveolar ridges, left hand postaxial polydactyly, broad right hallux and left hallux duplication, and intermittent respiratory difficulty. Brain anomalies include vermis hypoplasia with molar tooth sign, agenesis of corpus callosum, and ventricular dilation. OFD15 inheritance is autosomal recessive.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD16 features include postaxial polydactyly of the hands and feet, multiple tongue cysts, and dysmorphic features, including frontal narrowing, short palpebral fissures, flat nasal bridge, retrognathia, and low-set ears. Neurologic features include delayed psychomotor development and severe cognitive impairment. OFD16 inheritance is autosomal recessive.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD17 inheritance is autosomal recessive.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD18 is an autosomal recessive form characterized by short stature, brachymesophalangy, pre- and postaxial polysyndactyly, and stocky femoral necks, as well as oral anomalies and dysmorphic facial features.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD19 is an autosomal recessive form characterized by tongue nodules, dental and digital anomalies, narrow high-arched or cleft palate, and retrognathia. Some patients have notching of the upper or lower lip.
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD4 patients have tongue nodules, multiple frenulae, broad flat nose, hypertelorism, and short rib polydactyly with tibial dysplasia (Majewski syndrome). The presence of severe tibial aplasia differentiates OFD4 from OFD1. Additional features of cystic dysplastic kidneys and brain malformation, including occipital encephalocele, are observed in severely affected patients.
Polydactyly, postaxial, with median cleft of upper lip
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD5 patients show the core features of cleft palate, lobulated tongue, and polydactyly. Additional features include frontal bossing and intellectual disability.
Polydactyly, cleft lip/palate or lingual lump, and psychomotor retardation
A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD6 is characterized by metacarpal abnormalities with central polydactyly, cerebellar abnormalities including the molar tooth sign, tongue hamartomas, additional frenula, and upper lip notch.
Orotate phosphoribosyltransferase and orotidylic decarboxylase deficiency
Orotidylic pyrophosphorylase and orotidylic decarboxylase deficiency
Uridine monophosphate synthase deficiency
A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies.
A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia.
An autosomal recessive disorder characterized by severe orthostatic hypotension apparent from infancy or early childhood, low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. Some patients may also have renal dysfunction and reduced life expectancy. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope.
Syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high.
Ossification of the posterior longitudinal ligament of the spine
A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis.
A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement.
Osteoarthritis of distal interphalangeal joints
A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. In the hand, osteoarthritis can develop in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints. Patients with osteoarthritis may have one, a few, or all of these sites affected.
Osteoarthritis with mild chondrodysplasia
Osteoarthritis is a common disease that produces joint pain and stiffness together with radiologic evidence of progressive degeneration of joint cartilage.
Osteochondrodysplasia, brachydactyly, and overlapping malformed digits
An autosomal recessive disorder characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum.
Osteochondrodysplasia, complex lethal, Symoens-Barnes-Gistelinck type
An autosomal recessive, lethal syndrome characterized by severe hypomineralization of the entire skeleton, severe osteopenia, microcephaly, multiple intra-uterine fractures, and multiple congenital developmental anomalies affecting the brain, lungs, and kidneys.
Bowing of tibia with pseudarthrosis and pectus excavatum
A congenital disorder of osteogenesis characterized by non-neoplastic, radiolucent lesions that affect the cortical bone immediately under the periosteum. It usually manifests as a painless swelling or anterior bowing of the long bones, most commonly the tibia and fibula.
Osteogenesis imperfecta with blue sclerae
An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI1 is a non-deforming form with normal height or mild short stature, and no dentinogenesis imperfecta.
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI10 is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclerae.
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI11 is an autosomal recessive form.
Osteogenesis imperfecta Sillence type III
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI12 is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, no dentinogenesis imperfecta, normal hearing, and white sclerae.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI13 is characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, severe bone deformity, and recurrent fractures affecting both upper and lower limbs.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI14 is characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI15 is characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclerae. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients.
Chromosome 11p11.2 deletion syndrome, 91.3-KB
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI16 is a severe form.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI18 is a severe form characterized by congenital bowing of the lower limb, wormian bones, blue sclerae, vertebral collapses and multiple fractures in the first years of life.
An X-linked form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI19 is characterized by prenatal fractures, short stature, white sclerae, variable scoliosis and pectal deformity, striking tibial anterior angulation and generalized osteopenia.
Osteogenesis imperfecta congenita perinatal lethal form
Osteogenesis imperfecta type II autosomal dominant
An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI2 is characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI20 is a progressive deforming form characterized by osteopenia, skeletal deformity, healed fractures, and newly-acquired fractures. Death due to respiratory failure can occur in some patients.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI21 is a progressively deforming form characterized by multiple fractures appearing at birth or early childhood.
An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI22 is a severe form of the disease.
Progressively deforming osteogenesis imperfecta with normal sclerae
An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI3 is characterized by progressively deforming bones, very short stature, a triangular face, severe scoliosis, grayish sclera and dentinogenesis imperfecta.
Osteogenesis imperfecta with normal sclerae
An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI4 is characterized by moderately short stature, mild to moderate scoliosis, grayish or white sclera and dentinogenesis imperfecta.
An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI5 patients manifest moderate to severe bone fragility, calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation.
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI6 is a severe, autosomal recessive form compatible with OI type III in the Sillence classification.
Osteogenesis imperfecta perinatal lethal autosomal recessive
Osteogenesis imperfecta type II autosomal recessive
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI7 is an autosomal recessive, severe form. Multiple fractures are present at birth and patients have short stature, short humeri and femora, coxa vara, and white sclera. Dentinogenesis imperfecta is absent. Death can occur in the perinatal period due to secondary respiratory insufficiency.
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI8 is characterized by disproportionate short stature, severe osteoporosis, shortening of the long bones, white sclerae, a round face and a short barrel-shaped chest.
Osteogenesis imperfecta Sillence type II/III without abnormality of type I collagen
A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI9 is a severe autosomal recessive form of the disorder.
A sarcoma originating in bone-forming cells, affecting the ends of long bones.
Characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.
An autosomal recessive disorder characterized by cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Some patients also display mild developmental delay and intellectual disability.
Osteopathia striata with cranial sclerosis
Hyperostosis generalisata with striations
An X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, facial palsy, conductive hearing loss, mild learning disabilities, sclerosis of the long bones and skull. Longitudinal striations are visible on radiographs of the long bones, pelvis, and scapulae (osteopathia striata). In males this entity is usually associated with fetal or neonatal lethality. Occasional surviving males have, in addition to hyperostosis, cardiac, intestinal, and genitourinary malformations.
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate.
Autosomal dominant Albers-Schonberg disease
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. It is characterized by sclerosis, predominantly involving the spine, the pelvis and the skull base.
A form of osteopetrosis, a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and an autosomal dominant form occurring in adolescence or adulthood. OPTA3 is characterized by typical features of osteopetrosis such as fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density. Some patients exhibit localized osteosclerosis and generalized osteopenia.
Autosomal recessive Albers-Schonberg disease
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB2 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development.
Carbonic anhydrase II deficiency syndrome
Osteopetrosis with renal tubular acidosis
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with intellectual disability.
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB5 patients manifest primary central nervous system involvement in addition to the classical stigmata of severe bone sclerosis, growth failure, anemia, thrombocytopenia and visual impairment with optic atrophy.
Autosomal recessive osteopetrosis intermediate form
Osteoclast-poor osteopetrosis with hypogammaglobulinemia
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB7 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. OPTB7 is associated with hypogammaglobulinemia.
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB8 is clinically characterized by dense bones with no distinction between outer and inner plates, due to extensive encroachment of cortical bone into the medullary space, increased head circumference, broad open fontanelle, frontal bossing, and hepatosplenomegaly. Osteoclasts number is low and their bone resorptive capacity is impaired.
A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs.
Osteoporosis, childhood- or juvenile-onset, with developmental delay
An autosomal dominant disorder characterized by decreased bone mass and deterioration of bone microarchitecture, fragile bones, recurrent fractures following minor trauma, and developmental delay of variable severity.
A disease characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures. Additional clinical manifestations may include microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, intellectual disability and hypotonia.
An autosomal recessive skeletal dysplasia characterized by osteosclerosis at multiple skeletal sites, predominantly at the metaphyses of the long bones and vertebral bodies.
An inflammation of the middle ear resulting in earache, fever, hearing disturbance, and vertigo.
A disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability.
Otofaciocervical syndrome 2, with T-cell deficiency
An autosomal recessive disorder characterized by facial dysmorphism, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability. Some patients also exhibit altered thymus development with T-cell immunodeficiency.
X-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild intellectual disability, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto-palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Remodeling of the cytoskeleton is central to the modulation of cell shape and migration. FLNA is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers. Males with OPD1 have cleft palate, malformations of the ossicles causing deafness and milder bone and limb defects than those associated with OPD2. Obligate female carriers of mutations causing both OPD1 and OPD2 have variable (often milder) expression of a similar phenotypic spectrum.
Congenital bone disorder that is characterized by abnormally modeled, bowed bones, small or absent first digits and, more variably, cleft palate, posterior fossa brain anomalies, omphalocele and cardiac defects.
Otospondylomegaepiphyseal dysplasia, autosomal dominant
Pierre Robin syndrome with fetal chondrodysplasia
An autosomal dominant form of otospondylomegaepiphyseal dysplasia, a disorder characterized by sensorineural deafness, enlarged epiphyses, mild platyspondyly, and disproportionate shortness of the limbs. Total body length is normal. Typical facial features are mid-face hypoplasia, short upturned nose and depressed nasal bridge. Most patients have Pierre Robin sequence including an opening in the roof of the mouth (cleft palate) and a small lower jaw (micrognathia). Ocular symptoms are absent. Some patients have early-onset osteoarthritis.
Otospondylomegaepiphyseal dysplasia, autosomal recessive
Chondrodystrophy with sensorineural deafness
An autosomal recessive form of otospondylomegaepiphyseal dysplasia, a disorder characterized by sensorineural deafness, enlarged epiphyses, mild platyspondyly, and disproportionate shortness of the limbs. Total body length is normal. Typical facial features are mid-face hypoplasia, short upturned nose and depressed nasal bridge. Most patients have Pierre Robin sequence including an opening in the roof of the mouth (cleft palate) and a small lower jaw (micrognathia). Ocular symptoms are absent. Some patients have early-onset osteoarthritis.
Ovalocytosis, Malaysian-Melanesian-Filipino type
An autosomal dominant hematologic disorder characterized by ovalocytic erythrocytes that are rigid and exhibit reduced expression of many erythrocyte antigens. Clinical manifestations include mild hemolysis, intermittent jaundice and gallstones. However, the disorder is most often asymptomatic.
The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
Hypergonadotropic ovarian dysgenesis autosomal recessive
Hypergonadotropic ovarian dysgenesis with normal karyotype
An autosomal recessive disease characterized by primary amenorrhea, variable development of secondary sex characteristics, poorly developed streak ovaries, and high serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
An autosomal recessive form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads.
Ovarian failure hypergonadotropic due to ovarian dysgenesis
X-linked hypergonadotropic ovarian dysgenesis
A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads.
A form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG4 is an autosomal recessive condition.
A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG5 is an autosomal recessive condition.
A form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG6 is an autosomal recessive condition.
A form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG7 is an autosomal recessive condition.
An autosomal dominant form of ovarian dysgenesis, a disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads.
Disorder which occurs either spontaneously or most often as an iatrogenic complication of ovarian stimulation treatments for in vitro fertilization. The clinical manifestations vary from abdominal distention and discomfort to potentially life-threatening, massive ovarian enlargement and capillary leak with fluid sequestration. Pathologic features of this syndrome include the presence of multiple serous and hemorrhagic follicular cysts lined by luteinized cells, a condition called hyperreactio luteinalis.
Hereditary, overhydrated, cation-leak stomatocytosis
Potassium sodium disorder of erythrocyte
An autosomal dominant disorder of red cell membrane permeability to monovalent cations, characterized by macrocytic hemolytic anemia of fluctuating severity, circulating erythrocytes with slit-like lucencies (stomata) evident on fixed, stained peripheral blood smears. OHST red cells exhibit cation leak, resulting in elevated cell sodium content with reduced potassium content. The disease is marked by splenomegaly or hepatosplenomegaly, cholelithiasis and a strong tendency for iron overload.
Heritable disorder of connective tissue characterized by involvement of the mitral valve, aorta, skeleton, and skin. MASS syndrome is closely resembling both the Marfan syndrome and the Barlow syndrome. However, no dislocation of the lenses or aneurysmal changes occur in the aorta, and the mitral valve prolapse is by no means invariable.
Hemolytic anemia due to UMPH1 deficiency
Autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties.
Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures
An autosomal recessive disorder characterized by global developmental delay, variably impaired intellectual development, speech delay, facial dysmorphism, microcephaly, and varying degrees of cortical malformations including pachygyria, thin corpus callosum and subcortical band heterotopia. Most patients have generalized seizures.
Pachyonychia congenita Jadassohn-Lewandowsky type
An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma, follicular hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the hands and feet is usually present.
Pachyonychia congenita Jackson-Lawler type
An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma and hyperhidrosis, follicular hyperkeratosis, multiple epidermal cysts, absent/sparse eyebrow and body hair, and by the presence of natal teeth.
An autosomal dominant genodermatosis characterized by hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts.
An X-linked, syndromic, neurodevelopmental disorder characterized by intellectual disability, global developmental delay, severe myopia, and mild facial dysmorphism.
A form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.
A disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.
Chronic congenital idiopathic hyperphosphatasia
Hyperostosis corticalis deformans juvenilis
An autosomal recessive, juvenile-onset form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. PDB5 clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness.
An autosomal dominant form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. PDB6 is characterized by adult onset of bone pain associated with polyostotic bone lesions primarily affecting the axial skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone.
Hypothalamic hamartoblastoma hypopituitarism imperforate anus and postaxial polydactyly
An autosomal recessive disorder characterized by a wide phenotypic spectrum of developmental anomalies affecting the brain, heart, skeleton and enteric nervous system. Clinical features include hypothalamic hamartoma, microcephaly, atrioventricular septal defect, postaxial polydactyly, narrow chest, shortening of long bones, and aganglionosis.
Palmoplantar carcinoma, multiple self-healing
Corneal intraepithelial dyskeratosis and ectodermal dysplasia
An autosomal dominant disease characterized by keratopathy with neovascularization, bilateral corneal opacification, palmoplantar hyperkeratosis, dyshidrosis, dystrophic nails, and recurrent keratoacanthomas in palmoplantar skin as well as in conjunctival and corneal epithelia. In addition, patients experience a high susceptibility to malignant squamous cell carcinoma.
Palmoplantar keratoderma 1, striate, focal, or diffuse
Keratoderma, palmoplantar, striate form I
A dermatological disorder characterized by thickening of the skin on the palms and soles, and longitudinal hyperkeratotic lesions on the palms, running the length of each finger.
Palmoplantar keratoderma and congenital alopecia 1
Keratoderma-hypotrichosis-leukonychia totalis syndrome
A rare autosomal dominant disorder characterized by severe hyperkeratosis of the palms and soles, and congenital hypotrichosis or alopecia. Dystrophic nail changes occur in some patients.
Palmoplantar keratoderma and woolly hair
A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe.
Palmoplantar keratoderma, non-epidermolytic, focal 2
A dermatological disorder characterized by non-epidermolytic, abnormal thickening of the skin on the palms and soles. Focal palmoplantar keratoderma consists of localized areas of hyperkeratosis located mainly on pressure points and sites of recurrent friction.
Palmoplantar keratoderma, non-epidermolytic, focal or diffuse
Nonepidermolytic focal or diffuse palmoplantar keratoderma
A dermatological disorder characterized by non-epidermolytic abnormal thickening of the skin on the palms and soles. Diffuse palmoplantar keratoderma is characterized by uniform involvement of the palmoplantar surface, while the focal form consists of localized areas of hyperkeratosis located mainly on pressure points and sites of recurrent friction.
A disease characterized by isolated hypoplasia or agenesis of the pancreas, pancreatic beta-cell failure resulting in neonatal insulin-dependent diabetes mellitus, and exocrine pancreatic insufficiency.
Pancreatic agenesis and congenital heart defects
Congenital pancreatic agenesis with diabetes mellitus and congenital heart disease
Heart defects, congenital, and other congenital anomalies
An autosomal dominant disease characterized by pancreatic severe hypoplasia or agenesis, diabetes mellitus, and congenital heart abnormalities including ventricular septal defect, patent ductus arteriosus, pulmonary artery stenosis, truncus arteriosus and tetralogy of Fallot.
Diabetes mellitus and cerebellar hypoplasia/agenesis
Permanent neonatal diabetes mellitus with cerebellar agenesis
A disease characterized by neonatal diabetes mellitus, cerebellar agenesis or hypoplasia, severe intrauterine growth retardation, the presence of very little subcutaneous fat, and dysmorphic facial features.
A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
An autosomal recessive disorder characterized by exocrine pancreatic failure. Clinical findings include oily/greasy stools from infancy or early childhood, absence of discernible pancreatic disease, and significantly decreased pancreatic lipolytic activity.
A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks.
Affected individuals have absent infundibulum, anterior pituitary hypoplasia, and ectopic posterior pituitary.
Pyogenic sterile arthritis, pyoderma gangrenosum and acne
Characterized by autosomal dominant inheritance of early-onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction.
A benign tumor of neuroectodermal origin that generally occurs in childhood, but has also been reported in adults. Although generally found within the ventricular system, choroid plexus papillomas can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. Patients present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures.
Keratosis palmoplantaris with periodontopathia
An autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees.
CAKUT with or without ocular abnormalities
Coloboma of optic nerve with renal disease
Congenital anomalies of the kidney and urinary tract with or without ocular abnormalities
Optic coloboma vesicoureteral reflux and renal anomalies
Renal-coloboma syndrome with macular abnormalities
An autosomal dominant disorder characterized by both ocular and renal anomalies, but may also include vesicoureteral reflux, high frequency hearing loss, central nervous system anomalies, and/or genital anomalies. Eye anomalies in this disorder consist of a wide and sometimes excavated dysplastic optic disk with the emergence of the retinal vessels from the periphery of the disk, designated optic nerve coloboma or 'morning glory' anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst, microphthalmia, and pigmentary macular dysplasia. The kidneys are small and abnormally formed (renal hypodysplasia), and have fewer than the normal number of glomeruli, which are enlarged (oligomeganephronia). These ocular and renal anomalies result in decreased visual acuity and retinal detachment, as well as hypertension, proteinuria, and renal insufficiency that frequently progresses to end-stage renal disease.
Paraganglioma and gastric stromal sarcoma
Paraganglioma and gastrointestinal stromal tumor
Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.
Familial non-chromaffin paragangliomas 1
Familial paragangliomas non-chromaffin 1 with or without deafness
A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. PGL1 is a rare autosomal dominant disorder which is characterized by the development of mostly benign, highly vascular, slowly growing tumors in the head and neck. In the head and neck region, the carotid body is the largest of all paraganglia and is also the most common site of the tumors.
Familial non-chromaffin paragangliomas 2
A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas can develop at various body sites, including the head, neck, thorax and abdomen. Most commonly, they are located in the head and neck region, specifically at the carotid bifurcation, the jugular foramen, the vagal nerve, and in the middle ear.
Familial non-chromaffin paragangliomas 3
Carotid body tumors and multiple extraadrenal pheochromocytomas
Pheochromocytoma extraadrenal and cervical paraganglioma
An autosomal dominant tumor predisposition syndrome characterized by adult-onset development of paragangliomas, neural crest tumors usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas can develop at various body sites, including the head, neck, thorax and abdomen. Some of the tumors may secrete biologically active normetanephrine, resulting in secondary hypertension. PGL6 patients are at high risk for metastatic disease.
An autosomal dominant tumor predisposition syndrome characterized by adult-onset development of paragangliomas, neural crest tumors usually derived from the chromoreceptor tissue of a paraganglion. PGL7 tumors are generally benign, tend to be abdominal, and often secrete normetanephrine.
Paramyotonia congenita without cold paralysis
An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP.
A bone dysplasia characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. Radiographically, the disease is characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses and apophyses.
These cancers characteristically result in more profound clinical manifestations of hyperparathyroidism than do parathyroid adenomas, the most frequent cause of primary hyperparathyroidism. Early en bloc resection of the primary tumor is the only curative treatment.
Parenti-Mignot neurodevelopmental syndrome
An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, speech delay, motor delay, behavioral problems, and epilepsy.
Autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month.
Autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM2 is also a clinical feature of Potocki-Shaffer syndrome.
Parietal foramina with cleidocranial dysplasia
Cleidocranial dysplasia with parietal foramina
Combines skull defects in the form of enlarged parietal foramina and deficient ossification of the clavicles.
A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
Parkinson disease 11, autosomal dominant, susceptibility to
A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Parkinson disease 14 autosomal recessive
An adult-onset progressive neurodegenerative disorder characterized by parkinsonism, dystonia, severe cognitive decline, cerebral and cerebellar atrophy and absent iron in the basal ganglia on magnetic resonance imaging.
Parkinson disease 15 autosomal recessive
A neurodegenerative disorder characterized by parkinsonian and pyramidal signs. Clinical manifestations include tremor, bradykinesia, rigidity, postural instability, spasticity, mainly in the lower limbs, and hyperreflexia.
An autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Parkinson disease 18, autosomal dominant, susceptibility to
An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
A juvenile form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK19A is characterized by onset of parkinsonian symptoms in the first or second decade of life. Some patients may have additional neurologic features, including intellectual disability and seizures.
An early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK19B is characterized by symptoms onset in the third-to-fifth decade, slow disease progression, and prominent. response to dopaminergic therapies. Inheritance is autosomal recessive.
Autosomal recessive early-onset Parkinson disease type 2
Autosomal recessive juvenile Parkinson disease
Chromosome 6-linked autosomal recessive parkinsonism
Early-onset parkinsonism with diurnal fluctuation
A neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, tremor, and onset usually before 40. It differs from classic Parkinson disease by early DOPA-induced dyskinesia, diurnal fluctuation of the symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is absent. Pathologically, patients show loss of dopaminergic neurons in the substantia nigra, similar to that seen in Parkinson disease; however, Lewy bodies (intraneuronal accumulations of aggregated proteins) are absent.
An early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK20 is characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia.
An autosomal dominant form of adult-onset Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Parkinson disease 22, autosomal dominant
An autosomal dominant form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Parkinson disease 23, autosomal recessive, early onset
An autosomal recessive, early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Parkinson disease 24, autosomal dominant
An autosomal dominant form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK24 shows incomplete penetrance.
Parkinson disease 4 autosomal dominant Lewy body
A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
Parkinson disease 5, autosomal dominant, susceptibility to
Autosomal recessive early-onset Parkinson disease type 6
Parkinson disease 6 late-onset susceptibility to
Parkinson disease autosomal recessive early-onset digenic PINK1/DJ1
An early-onset form of Parkinson disease, a neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive.
Amyotrophic lateral sclerosis-parkinsonism/dementia complex type 2
Autosomal recessive early-onset Parkinson disease type 7
A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).
A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.
Steele-Richardson-Olszewski syndrome atypical
Supranuclear palsy progressive 1 atypical
A syndrome characterized by parkinsonism, tremor, rigidity, dementia, ophthalmoparesis and pyramidal signs. Neurofibrillary degeneration occurs in the hippocampus, basal ganglia and brainstem nuclei.
An autosomal dominant disorder characterized by late-onset, levodopa-responsive parkinsonism with asymmetric tremor, rigidity and bradykinesia. Patients also manifest a sensorimotor polyneuropathy with variable degrees of distal legs and hands muscle atrophy and weakness, and absent deep tendon reflexes.
A syndrome characterized by parkinsonian features, such as cogwheel rigidity, resting tremor and bradykinesia, and variably penetrant spasticity.
Parkinsonism-dystonia 1, infantile-onset
Dopamine transporter deficiency syndrome
An autosomal recessive neurodegenerative disorder characterized by infantile onset of parkinsonism and dystonia. Other neurologic features include global developmental delay, bradykinesia and pyramidal tract signs.
Parkinsonism-dystonia 2, infantile-onset
An autosomal recessive disorder characterized by infantile onset of abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. Some patients have variable degrees of developmental delay.
Parkinsonism-dystonia 3, childhood-onset
An autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances.
Pain, submandibular, ocular, and rectal, with flushing
An autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing.
A disorder characterized by hemolytic anemia with hemoglobinuria, thromboses in large vessels, and a deficiency in hematopoiesis. Red blood cell breakdown with release of hemoglobin into the urine is manifested most prominently by dark-colored urine in the morning.
Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy
Generalized epilepsy and paroxysmal dyskinesia
An autosomal dominant neurologic disorder characterized by absence seizures, generalized tonic-clonic seizures, paroxysmal nonkinesigenic dyskinesia and involuntary dystonic or choreiform movements. Onset is usually in childhood. Patients may have seizures only, dyskinesia only, or both.
A rare childhood disease characterized by loss of subcutaneous fat from the face and trunk. Fat deposition on the pelvic girdle and lower limbs is normal or excessive. Most frequently, onset between 5 and 15 years of age. Most affected subjects are females and some show no other abnormality, but many develop glomerulonephritis, diabetes mellitus, hyperlipidemia, and complement deficiency. Intellectual disability in some cases. APLD is a sporadic disorder of unknown etiology.
Intellectual developmental disorder, X-linked, syndromic 1
An X-linked developmental disorder characterized by intellectual disability, episodic dystonic hand movements, lower limb spasticity, and dysarthria.
A congenital heart defect characterized by the persistent opening of fetal ductus arteriosus that fails to close after birth. Fetal ductus arteriosus connects the pulmonary artery to the descending aorta, allowing unoxygenated blood to bypass the lung and flow to the placenta. Normally, the ductus occludes shortly after birth.
Skin peeling familial continuous generalized
A genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels.
A non-inflammatory and localized form of peeling skin syndrome, a genodermatosis characterized by the continuous shedding of the outer layers of the epidermis. In PSS2 patients, skin peeling is painless and strictly limited to the dorsa of the hands and feet. It is accompanied by painless erythema and spontaneous non-scarring healing. Ultrastructural and histological analysis shows a level of blistering high in the epidermis at the stratum granulosum-stratum corneum junction.
A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS3 is characterized by generalized white scaling occurring over the upper and lower extremities. Symptoms start during the second half of the first decade of life.
Exfoliative ichthyosis, autosomal recessive
Exfoliative ichthyosis autosomal recessive IBS-like
Ichthyosis, exfoliative, autosomal recessive, ichthyosis bullosa of Siemens-like
A genodermatosis characterized by congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. PSS4 presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non-erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes.
A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS5 patients manifest hyperkeratosis and superficial peeling of areas of the palmar and dorsal faces of hands and feet. Additional variable features include erythema, superficial scaling of forearms and legs and diffuse yellowish hyperkeratotic palmoplantar plaques. PSS5 inheritance is autosomal recessive.
A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS6 patients manifest generalized ichthyotic dry skin, and bullous peeling lesions on the trunk and limbs at sites of minor trauma. Skin symptoms are exacerbated by warmth and humidity. PSS6 inheritance is autosomal recessive.
Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads
An autosomal recessive disease characterized by generalized, continuous shedding of the outer layers of the epidermis, leukonychia, acral punctate keratosis, cheilitis, knuckle pads with multiple hyperkeratotic micropapules involving the interphalangeal joints, and palmoplantar keratoderma.
Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy
An autosomal recessive syndrome characterized by progressive encephalopathy, lack of psychomotor development, severe intellectual disability, early onset epileptic seizures, optic nerve/cerebellar atrophy, pedal edema, and early death.
An autosomal recessive syndrome characterized by microcephaly and moderately severe hypotonia manifesting at birth, seizures that progress into infantile spasms with hypsarrhythmia, brain atrophy with bilateral polymicrogyria and pachygyria, thin corpus callosum, and mild reduction in cerebellar vermis volume. Patients also display optic atrophy, severe cognitive delay, puffiness of the maxillary region of the face, and edema of the dorsum of the hands and feet.
An autosomal dominant inherited abnormality of granulocytes, characterized by abnormal ovoid shape, reduced nuclear segmentation and an apparently looser chromatin structure.
An X-linked recessive hypomyelinating disorder of the central nervous system in which myelin is not formed properly. PMD is characterized clinically by nystagmus, spastic quadriplegia, ataxia, and developmental delay.
An autosomal recessive disorder characterized by congenital sensorineural hearing loss in association with thyroid goiter. The disorder may account for up to 10% of the cases of hereditary deafness. The deafness is most often associated with a Mondini cochlear defect. Deafness occurs early, starting at birth or during the first years of life. It is bilateral, sometimes asymmetrical, fluctuant and often progressive. Thyroid perturbations, such as thyroid goiter and/or hypothyroidism appear most commonly during adolescence, but they can be congenital or appear later.
An inborn error of metabolism characterized by excessive urinary excretion of L-xylulose.
Crisponi/Cold-induced sweating syndrome 3
An autosomal recessive multisystem disorder characterized by global developmental delay, dysmorphic facial features, feeding and respiratory difficulties with poor overall growth, axial hypotonia, and joint contractures. The features are variable, even within families, and may also include retinitis pigmentosa, cardiac or genitourinary anomalies, and abnormal sweating.
Periodic fever, familial, autosomal dominant
TNF receptor-associated periodic syndrome
Tumor necrosis factor receptor-associated periodic syndrome
A hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.
Periodic fever, immunodeficiency, and thrombocytopenia syndrome
An immunologic disorder with variable manifestations including early-onset recurrent respiratory infections, stomatitis, cutaneous infections, and neutropenia.
Periodic fever, menstrual cycle-dependent
A condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines.
Adynamia episodica hereditaria with or without myotonia
An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients.
An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.
A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness.
A disease characterized by severe and protracted gingival infections, generalized or localized, leading to tooth loss. Amounts of microbial deposits are generally inconsistent with the severity of periodontal tissue destruction and the progression of attachment and bone loss may be self arresting.
Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease
Waardenburg-Shah syndrome neurologic variant
A complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease.
Peripheral motor neuropathy, childhood-onset, biotin-responsive
An autosomal recessive disorder characterized by distal muscle weakness and atrophy appearing late in the first decade of life. The disorder predominantly affects the upper limbs and hands, resulting in difficulties with fine motor skills. Some patients may have lower limb involvement, resulting in gait difficulties. Additional features may include spasticity, ataxia, and cerebellar signs. Sensation is intact, and patients have normal cognitive development. Treatment with biotin, pantothenic acid, and lipoic acid may result in clinical improvement.
Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay
Combined oxidative phosphorylation deficiency 26
An autosomal recessive mitochondrial disorder with multisystemic and highly variable manifestations. Affected individuals suffer from a peripheral neuropathy, with distal muscle weakness and atrophy, and distal sensory impairment. Additional variable features include early-onset hypotonia and global developmental delay, poor or absent motor skills, exercise intolerance, poor growth, cerebellar signs, spasticity, and seizures. Biochemical analysis may show deficiencies in mitochondrial respiratory complex. Lactic acidosis is frequently observed.
Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development
An autosomal recessive disorder characterized by early childhood-onset of peripheral sensorimotor neuropathy, progressive distal muscle weakness, atrophy in hands and feet, and gait difficulties, often with loss of ambulation. Most affected individuals also have impaired intellectual development, although some have normal cognition. Additional features may include eye movement abnormalities, claw hands, foot deformities, and scoliosis.
Peripheral neuropathy, myopathy, hoarseness, and hearing loss
A complex phenotype of progressive peripheral neuropathy and distal myopathy, with later onset of hoarseness and hearing loss. Affected individuals develop distal muscle weakness at a mean age of 10.6 years, followed by progressive atrophy of these muscles. The lower limbs are more severely affected than the upper limbs, and the muscle weakness first affects anterior leg muscles and later posterior leg muscles.
Nodular heterotopia bilateral periventricular
Periventricular heterotopia Ehlers-Danlos variant
Periventricular heterotopia X-linked dominant
A developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH1 is an X-linked dominant form. Heterozygous females have normal intelligence but suffer from seizures and various manifestations outside the central nervous system, especially related to the vascular system. Hemizygous affected males die in the prenatal or perinatal period.
Autosomal recessive periventricular nodular heterotopia type 2
Periventricular heterotopia autosomal recessive
Periventricular heterotopia with microcephaly autosomal recessive
A developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH2 is an autosomal recessive form characterized by microcephaly (small brain), severe developmental delay and recurrent infections. No anomalies extrinsic to the central nervous system, such as dysmorphic features or grossly abnormal endocrine or other conditions, are associated with PVNH2.
A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH6 results in delayed psychomotor development, delayed speech, strabismus, and onset of seizures with hypsarrhythmia in early infancy.
A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH7 is an autosomal dominant disease characterized by delayed psychomotor development, intellectual disability, and seizures in some patients. Additional features include cleft palate and toe syndactyly.
A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH8 is an autosomal dominant disease characterized by developmental disabilities, speech delay, seizures and attention deficit hyperactivity disorder.
A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH9 is an autosomal dominant disorder with incomplete penetrance, characterized by impaired intellectual development, cognitive defects, learning disabilities, and behavior abnormalities. Some patients develop seizures.
Nephroblastomatosis fetal ascites macrosomia and Wilms tumor
Renal hamartomas nephroblastomatosis and fetal gigantism
An autosomal recessive congenital overgrowth syndrome. Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor. Histologic examination of the kidneys in affected children shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor.
Peroxisomal fatty acyl-CoA reductase 1 disorder
An autosomal recessive metabolic disorder clinically characterized by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity.
Peroxisome biogenesis disorder 10A (Zellweger)
A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.
A moderately severe peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD10B is characterized by neonatal jaundice, dysmorphic features, delayed psychomotor development, axial hypotonia that can progress to severe spastic paraparesis with hyperreflexia, nephrocalcinosis, neurogenic bladder, nystagmus, and cataracts. Laboratory studies show increased levels of very long-chain fatty acids. Inheritance is autosomal recessive.
Peroxisome biogenesis disorder 11A (Zellweger)
Peroxisome biogenesis disorder 11B (NALD/IRD)
Peroxisome biogenesis disorder 11B (neonatal adrenoleukodystrophy/infantile Refsum disease)
A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid.
Peroxisome biogenesis disorder 12A (Zellweger)
Peroxisome biogenesis disorder 13A (Zellweger)
An autosomal recessive peroxisome biogenesis disorder characterized clinically by mild intellectual disability, congenital cataracts, progressive hearing loss, and polyneuropathy. Additionally, recurrent migraine-like episodes following mental stress or physical exertion, not a common feature in peroxisome disorders, are observed.
Peroxisome biogenesis disorder 1A (Zellweger)
A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD1A is an autosomal recessive systemic disorder characterized clinically by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.
Peroxisome biogenesis disorder (NALD/IRD)
Peroxisome biogenesis disorder (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 1B (NALD/IRD)
Peroxisome biogenesis disorder 2A (Zellweger)
A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.
Peroxisome biogenesis disorder 2B (NALD/IRD)
Peroxisome biogenesis disorder 2B (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 3A (Zellweger)
Peroxisome biogenesis disorder 3B (NALD/IRD)
Peroxisome biogenesis disorder 3B (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 4A (Zellweger)
Peroxisome biogenesis disorder 4B (NALD/IRD)
Peroxisome biogenesis disorder 4B (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 5A (Zellweger)
Peroxisome biogenesis disorder 5B (NALD/IRD)
Peroxisome biogenesis disorder 5B (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 6A (Zellweger)
Peroxisome biogenesis disorder 6B (NALD/IRD)
Peroxisome biogenesis disorder 6B (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 7A (Zellweger)
Peroxisome biogenesis disorder 7B (NALD/IRD)
Peroxisome biogenesis disorder 7B (neonatal adrenoleukodystrophy/infantile Refsum disease)
Peroxisome biogenesis disorder 8A (Zellweger)
A relatively mild peroxisome biogenesis disorder. Affected individuals manifest lower limb spasticity and ataxia resulting in wheelchair dependence. Other features include optic atrophy, cataracts, dysarthria, dysphagia, constipation, and a peripheral demyelinating motor and sensory neuropathy. Cognition is relatively preserved. Biochemical abnormalities are mild and include increased very-long-chain fatty acids (VLCFA), increased bile acid intermediates, and increased branched chain fatty acids. Phytanic acid alpha-oxidation, pristanic acid beta-oxidation, and red cell plasmalogen are normal.
Atypical peroxisome biogenesis disorder PEX7-related
A peroxisome biogenesis disorder with unusually mild clinical and biochemical manifestations. Affected individuals manifest a variable phenotype similar to, and in some cases indistinguishable from, classic Refsum disease. Variable features include ocular abnormalities, sensorimotor neuropathy, ichthyosis, deafness, chondrodysplasia punctata without rhizomelia or growth failure.
Peroxisome biogenesis disorder complementation group 1
Peroxisome biogenesis disorder complementation group E
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 11
Peroxisome biogenesis disorder complementation group R
Peroxisome biogenesis disorder complementation group 12
Peroxisome biogenesis disorder complementation group G
Peroxisome biogenesis disorder complementation group 13
Peroxisome biogenesis disorder complementation group H
Peroxisome biogenesis disorder complementation group 14
Peroxisome biogenesis disorder complementation group J
Peroxisome biogenesis disorder complementation group 2
Peroxisome biogenesis disorder complementation group 3
Peroxisome biogenesis disorder complementation group 4
Peroxisome biogenesis disorder complementation group 6
Peroxisome biogenesis disorder complementation group C
Peroxisome biogenesis disorder complementation group 5
Peroxisome biogenesis disorder complementation group 10
Peroxisome biogenesis disorder complementation group F
Peroxisome biogenesis disorder complementation group 7
Peroxisome biogenesis disorder complementation group B
Peroxisome biogenesis disorder complementation group 8
Peroxisome biogenesis disorder complementation group A
Peroxisome biogenesis disorder complementation group 9
Peroxisome biogenesis disorder complementation group D
Peroxisome biogenesis disorder complementation group K
Gonadal dysgenesis XX type with deafness
Ovarian dysgenesis with sensorineural deafness
A sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild intellectual disability and cerebellar and peripheral nervous system involvement.
A sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.
A sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some PRLTS3 affected individuals.
An autosomal recessive, sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.
A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.
A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. PRLTS6 inheritance is autosomal recessive.
Parkinsonism with alveolar hypoventilation and mental depression
A neuropsychiatric disorder characterized by mental depression not responsive to antidepressant drugs or electroconvulsive therapy, sleep disturbances, exhaustion and marked weight loss. Parkinsonism develops later and respiratory failure occurred terminally.
Persistent hyperplastic primary vitreous, autosomal recessive
Congenital non-syndromic retinal non-attachment
Retinal non-attachment and falciform detachment
A developmental eye malformation associated with microphthalmia, cataract, glaucoma, and congenital retinal non-attachment. It is due to failure of the primary vitreous to regress in utero, resulting in the presence of a retrolental fibrovascular membrane with persistence of the posterior portion of the tunica vasculosa lentis and hyaloid artery. Disease manifestations range from a trivial remnant of hyaloid vessels to a dense fibrovascular mass causing lens opacity and retinal detachment.
Persistent Muellerian duct syndrome type I
A form of male pseudohermaphroditism characterized by a failure of Muellerian duct regression in otherwise normal males.
Persistent Muellerian duct syndrome type II
Persistent polyclonal B-cell lymphocytosis
An autosomal recessive disorder characterized by anterior eye-chamber abnormalities, disproportionate short stature, developmental delay, characteristic craniofacial features, cleft lip and/or palate.
An X-linked syndrome characterized by intellectual disability and additional highly variable features, including choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain. Intellectual disability is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
An autosomal dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer.
A syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).
A developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior, and minor dysmorphic features.
Autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes intellectual disability (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.
A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent.
Phosphoenolpyruvate carboxykinase deficiency, cytosolic
An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, hypoglycemia, hypotonia, hepatomegaly, hepatic dysfunction, failure to thrive, lactic acidosis, and elevated tricarboxylic acid intermediates, particularly fumarate, in urine.
Phosphoglycerate dehydrogenase deficiency
An autosomal recessive inborn error of L-serine biosynthesis, clinically characterized by congenital microcephaly, psychomotor retardation, and seizures.
A condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.
A condition characterized by elevated phosphohydroxylysine in the urine. There is no clinical phenotype associated with this finding other than the urinary metabolites.
Phosphoribosylaminoimidazole carboxylase deficiency
An autosomal recessive inborn error of purine metabolism, clinically characterized by multiple congenital anomalies and early neonatal death.
Phosphoribosylpyrophosphate synthetase superactivity
Familial disorder characterized by excessive purine production, gout and uric acid urolithiasis.
Phosphoserine aminotransferase deficiency
Characterized biochemically by low plasma and cerebrospinal fluid concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation.
An autosomal recessive disorder that results in pre- and postnatal growth retardation, moderate psychomotor retardation and facial features suggestive of Williams syndrome.
Dementia with lobar atrophy and neuronal cytoplasmic inclusions
A rare form of dementia pathologically defined by severe atrophy, neuronal loss and gliosis. It is characterized by the occurrence of tau-positive inclusions, swollen neurons (Pick cells) and argentophilic neuronal inclusions known as Pick bodies that disproportionally affect the frontal and temporal cortical regions. Clinical features include aphasia, apraxia, confusion, anomia, memory loss and personality deterioration.
Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.
Plantar lipomatosis, unusual facies, and developmental delay
An autosomal dominant syndrome characterized by multiple congenital anomalies, global developmental delay, learning disability, palmar and plantar fat pads, and distinctive facial characteristics, especially when smiling.
Microcoria-congenital nephrotic syndrome
An autosomal recessive disorder characterized by nephrotic syndrome with neonatal onset, diffuse mesangial sclerosis, and eye abnormalities with microcoria and hypoplasia of the ciliary and pupillary muscles. Death usually occurs within the first weeks of life. Patients who survive tend to show neurodevelopmental delay and visual loss.
Pigmentary disorder, reticulate, with systemic manifestations, X-linked
An X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines.
Pigmented paravenous chorioretinal atrophy
Unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. PPCRA is dominantly inherited, but exhibited variable expressivity. Males are more likely to exhibit a severe phenotype, whereas females may remain virtually asymptomatic even in later years. The PPCRA phenotype is associated with a mutation in CRB1 gene which is likely to affect the structure of the CRB1 protein.
Developmental delay and speech apraxia with or without seizures
An autosomal dominant disorder characterized by developmental delay, speech apraxia, intellectual disability, autism, and facial dysmorphic features. Some patients may have seizures.
Encephalopathy severe epileptic with autonomic dysfunction
A syndrome characterized by intellectual disability, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea. Features include intellectual disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing anomalies, severe motor developmental delay, motor incoordination, ocular anomalies, constipation, seizures, typical behavior and subtle brain abnormalities.
A syndrome characterized by severe intellectual disability and variable additional symptoms, such as impaired speech development, seizures, autistic behavior, breathing anomalies and a broad mouth, resembling Pitt-Hopkins syndrome. In contrast to patients with Pitt-Hopkins syndrome, PTHSL1 patients present with normal or only mildly to moderately delayed motor milestones.
A syndrome characterized by severe intellectual disability and variable additional symptoms, such as impaired speech development, autistic behavior, breathing anomalies and a broad mouth, resembling Pitt-Hopkins syndrome. Other features include decreased reflexes in the upper extremities, constipation, strabismus, and protruding tongue with drooling. In contrast to patients with Pitt-Hopkins syndrome, PTHSL2 patients present with normal or only mildly to moderately delayed motor milestones.
Pituitary adenoma, growth hormone-secreting, 1
A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete: growth hormone (GH)-secreting, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid- stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors. Familial and sporadic forms have been reported.
Pituitary adenoma 2, growth hormone-secreting
A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete. PITA2 is a growth hormone-secreting benign neoplasm, also known as somatotropinoma. It clinically results in acromegaly, a condition characterized by coarse facial features, protruding jaw, and enlarged extremities. Excessive production of growth hormone in children or adolescents before the closure of epiphyses causes gigantism, a condition characterized by abnormally tall stature.
A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete: growth hormone (GH)-secreting, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors. Familial and sporadic forms have been reported.
A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete. PITA4 results in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete: growth hormone (GH)-secreting, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors. Familial and sporadic forms have been reported. The transmission pattern of familial PITA5 is consistent with autosomal dominant inheritance with reduced penetrance.
Pituitary hormone deficiency, combined or isolated, 7
Growth hormone deficiency, isolated, type V
Isolated growth hormone deficiency, type V
An autosomal recessive deficiency of growth hormone characterized by severe postnatal growth failure, delayed bone age without bone dysplasia, and hypoplasia of the anterior pituitary.
Pituitary hormone deficiency, combined, 1
Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD1 is characterized by pleiotropic deficiencies of growth hormone, prolactin and thyroid-stimulating hormone, while the production of adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone are preserved. In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen. Some cases present with severe intellectual disability along with short stature.
Pituitary hormone deficiency, combined, 2
Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD2 is characterized by pleiotropic deficiencies of growth hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, prolactin and adrenocorticotropic hormone.
Pituitary hormone deficiency, combined, 3
Combined pituitary hormone deficiency with rigid cervical spine
Sensorineural deafness with pituitary dwarfism
Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD3 is characterized by a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation.
Pituitary hormone deficiency, combined, 4
Pituitary hormone deficiency combined with or without cerebellar defects
Short stature pituitary and cerebellar defects and small sella turcica
Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD4 is characterized by complete or partial deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone. Clinical features include short stature, cerebellar defects, and small sella turcica.
Pituitary hormone deficiency, combined, 5
Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD5 is characterized by complete or partial deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone.
Pituitary hormone deficiency, combined, 6
Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD6 patients manifest neonatal hypoglycemia, and deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone.
A rare, papulosquamous skin disease characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression. Familial PRP usually presents at birth or appears during the first years of life and runs a chronic course. It is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema.
Plasminogen activator inhibitor-1 deficiency
A hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen.
A disorder characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.
A disorder characterized by macrothrombocytopenia without notable hemostatic problems and bleeding tendency. Platelet glycoprotein IV deficiency can be divided into 2 subgroups. The type I phenotype is characterized by platelets and monocytes/macrophages exhibiting complete CD36 deficiency. The type II phenotype lacks the surface expression of CD36 in platelets, but expression in monocytes/macrophages is near normal.
Platelet-activating factor acetylhydrolase deficiency
An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. It can be associated with several disease states including inflammatory gastrointestinal disorders, asthma and atopy. Asthmatic individuals with PAFAD may manifest aggravated respiratory symptoms.
Platyspondylic lethal skeletal dysplasia Torrance type
Platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group of chondrodysplasias characterized by severe platyspondyly and limb shortening. PLSD-T is characterized by varying platyspondyly, short ribs with anterior cupping, hypoplasia of the lower ilia with broad ischial and pubic bones, and shortening of the tubular bones with splayed and cupped metaphyses. Histology of the growth plate typically shows focal hypercellularity with slightly enlarged chondrocytes in the resting cartilage and relatively well-preserved columnar formation and ossification at the chondro-osseous junction. PLSD-T is generally a perinatally lethal disease, but a few long-term survivors have been reported.
PPB familial tumor and dysplasia syndrome
A rare pediatric intrathoracic neoplasm. The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor.
Clericuzio-type poikiloderma neutropenia syndrome
Poikiloderma with neutropenia Clericuzio-type
A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-Thomson syndrome.
Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis
Hereditary sclerosing poikiloderma with tendon and pulmonary involvement
An autosomal dominant form of hereditary poikiloderma, a genodermatosis characterized by mottled pigmentation, telangiectasia, and epidermal atrophy. POIKTMP features include tendon contracture, myopathy, and progressive pulmonary fibrosis. It manifests from early childhood with telangiectasia and pigmentary anomalies especially on the face and sun-exposed areas, tendon contractures that particularly involve the ankles and feet causing gait disturbance, and development of pulmonary fibrosis during the second decade of life resulting in progressive dyspnea and restrictive impairment of lung function.
Poirier-Bienvenu neurodevelopmental syndrome
An autosomal dominant neurodevelopmental disorder characterized by onset of seizures in infancy, developmental delay, impaired intellectual development, and poor or absent speech.
Polycystic kidney disease 1 with or without polycystic liver disease
Autosomal dominant polycystic kidney disease 1
Potter type III polycystic kidney disease
An autosomal dominant disorder characterized by renal cysts, liver cysts and intracranial aneurysm. Clinical variability is due to differences in the rate of loss of glomerular filtration, the age of reaching end-stage renal disease and the occurrence of hypertension, symptomatic extrarenal cysts, and subarachnoid hemorrhage from intracranial 'berry' aneurysm.
Polycystic kidney disease 2 with or without polycystic liver disease
Autosomal dominant polycystic kidney disease 2
An autosomal dominant disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy.
Polycystic kidney disease 3 with or without polycystic liver disease
Polycystic kidney disease, adult, type III
A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occur in other organs, particularly the liver. PKD3 inheritance is autosomal dominant.
Polycystic kidney disease 4, with or without polycystic liver disease
Infantile polycystic kidney disease type I
Polycystic kidney disease, autosomal recessive
Polycystic kidney disease 4 with or without hepatic disease
A severe form of polycystic kidney disease affecting the kidneys and, in some cases, the hepatic biliary tract. The clinical spectrum is widely variable, with most cases presenting during infancy. The fetal phenotypic features classically include enlarged and echogenic kidneys, as well as oligohydramnios secondary to a poor urine output. Up to 50% of the affected neonates die shortly after birth, as a result of severe pulmonary hypoplasia and secondary respiratory insufficiency. In the subset that survives the perinatal period, morbidity and mortality are mainly related to severe systemic hypertension, renal insufficiency, and portal hypertension due to portal-tract fibrosis. PKD4 inheritance is autosomal recessive.
A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts may also occur in other organs, particularly the liver. PKD5 inheritance is autosomal recessive.
Polycystic kidney disease 6 with or without polycystic liver disease
A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occur in other organs, particularly the liver. PKD6 inheritance is autosomal dominant.
A form of polycystic kidney disease, a disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occur in other organs, particularly the liver. PKD7 inheritance is autosomal dominant.
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1
A recessively inherited disease characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usually leads to death in the fifth decade of life.
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2
An autosomal recessive disease characterized by presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years.
Polycystic liver disease 1 with or without kidney cysts
An autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. A subset of patients may develop kidney cysts that usually do not result in clinically significant renal disease.
Polycystic liver disease 2 with or without kidney cysts
Polycystic liver disease 3 with or without kidney cysts
A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. PCLD3 patients may also develop kidney cysts that usually do not result in clinically significant renal disease.
Polycystic liver disease 4 with or without kidney cysts
A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. PCLD4 patients may also develop kidney cysts that usually do not result in clinically significant renal disease.
A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly.
A condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal.
A condition characterized by an extra digit in the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type B the extra digit is not well formed and is frequently in the form of a skin.
A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA10 is an autosomal recessive condition characterized by one or more postaxial digits of the hands and/or feet. A rudimentary digit (PAP type B) may also be present. Intrafamilial variability has been observed.
A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA7 is an autosomal recessive condition characterized by postaxial polydactyly restricted to the feet.
A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA8 is an autosomal recessive condition characterized by the presence of postaxial extra digits (hexadactyly) on the hands and/or the feet.
A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA9 is an autosomal recessive condition characterized by one or more posterior or postaxial digits.
A form of polydactyly, a condition defined by the occurrence of supernumerary digits in the upper and/or lower extremities. Preaxial or radial polydactyly refers to the presence of extra digits on the radial side of the hand. PPD1 is an autosomal recessive form characterized by duplication of the distal phalanx of the thumb.
A form of polydactyly, a condition defined by the occurrence of supernumerary digits in the upper and/or lower extremities. Preaxial or radial polydactyly refers to the presence of extra digits on the radial side of the hand. PPD4 is an autosomal dominant form characterized by mild duplication of the thumb, syndactyly of various degrees affects fingers 3 and 4, duplication of part or all of the first or second toes and variable toes syndactyly. Some patients have only foot involvement.
A progressive endocrine and neurodevelopmental disorder manifesting early in childhood with growth retardation and recurrent episodes of profound asymptomatic hypoglycemia. PEPNS is characterized by central hypothyroidism, hypogonadotropic hypogonadism, incomplete puberty, progressive non-autoimmune insulin-dependent diabetes mellitus, peripheral demyelinating sensorimotor polyneuropathy, and cerebellar and pyramidal signs.
Polyglucosan body myopathy 1 with or without immunodeficiency
Polyglucosan body myopathy, early-onset, with or without immunodeficiency
A disease characterized by polyglucosan storage myopathy associated with early-onset progressive muscle weakness and progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. Some patients present with severe immunodeficiency, invasive bacterial infections and chronic autoinflammation.
A glycogen storage disease characterized by polyglucosan accumulation in muscle, and skeletal myopathy without cardiac involvement. Most patients manifest slowly progressive, hip girdle, shoulder girdle, and/or hand and leg muscle weakness. Polyglucosan contains abnormally long and poorly branched glucosyl chains and is variably resistant to digestion by alpha-amylase.
Polyglucosan body neuropathy, adult form
A late-onset, slowly progressive disorder affecting the central and peripheral nervous systems. Patients typically present after age 40 years with a variable combination of cognitive impairment, pyramidal tetraparesis, peripheral neuropathy, and neurogenic bladder. Other manifestations include cerebellar dysfunction and extrapyramidal signs. The pathologic hallmark of APBN is the widespread accumulation of round, intracellular polyglucosan bodies throughout the nervous system, which are confined to neuronal and astrocytic processes.
Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome
Polymicrogyria with or without vascular-type EDS
An autosomal recessive disorder with a highly variable phenotype and onset in early childhood. Disease features include cobblestone-like malformation of the cortex, polymicrogyria, intellectual and motor developmental delay, small joint hypermobility, vascular fragility, aneurysms, thin translucent skin and easy bruising, congenital heart defects, and foot deformities. Early death due to vascular dissection may occur.
Polymicrogyria, bilateral frontoparietal
Cerebellar ataxia with neuronal migration defect
A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination, most severe in the frontoparietal regions. BFPP clinical manifestations include developmental and psychomotor delay, cerebellar and pyramidal signs, truncal ataxia, seizures, hyperreflexia. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization.
Polymicrogyria, bilateral perisylvian, autosomal recessive
A form of polymicrogyria, a malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. BPPR is characterized by strikingly restricted polymicrogyria limited to the cortex surrounding the Sylvian fissure. Affected individuals have intellectual and language difficulty and seizures, but no motor disability. Polymicrogyria is a heterogeneous disorder, considered to be the result of post-migratory abnormal cortical organization.
Polymicrogyria, bilateral temporooccipital
A disease characterized by temporo-occipital polymicrogyria, psychiatric manifestations, and epilepsy.
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract
A slowly progressive neurologic disorder with a variable phenotype resembling Refsum disease. Clinical features include sensorineural hearing loss, visual problems related to cataracts, retinitis pigmentosa, pes cavus, ataxic and/or spastic gait disturbances with a progressive sensorimotor peripheral neuropathy. Other features include hyporeflexia, hyperreflexia, extensor plantar responses.
A disease characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Patients can develop polyps of multiple and mixed morphologies, including serrated lesions, Peutz-Jeghers polyps, juvenile polyps, conventional adenomas and colorectal carcinoma in the absence of any identifiable extra-colonic features.
A disease is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH10 features include cortical dysgenesis marked by a simplified gyral pattern, cortical atrophy, mild or focal cerebellar vermian volume loss, delayed myelination, progressive microcephaly, global growth and developmental delays, severe intellectual disabilities, and seizures refractory to treatment.
A non-degenerative form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH11 features include severely delayed psychomotor development with intellectual disability and poor speech, microcephaly, dysmorphic features, and pontocerebellar hypoplasia. PCH11 inheritance is autosomal recessive.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH12 is an autosomal recessive form characterized by onset in utero and death in infancy. Brain imaging shows microcephaly, cerebellar hypoplasia, micrognathia, and multiple contractures.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH13 is an autosomal recessive form characterized by delayed psychomotor development, absent speech, severe intellectual disability and postnatal microcephaly, with brain malformations consisting of cerebellar atrophy and hypoplastic corpus callosum. Additional features, including seizures and visual impairment, are variable.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH14 is a severe autosomal recessive form characterized by progressive microcephaly, and poor or absent psychomotor development with severely impaired intellectual development apparent from birth. Other features may include hypotonia, spastic quadriplegia, and early-onset seizures. Early death may occur in some patients.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH15 is a severe autosomal recessive form characterized by progressive microcephaly, and poor or absent psychomotor development with severely impaired intellectual development apparent from birth. Other features may include spastic quadriplegia, early-onset seizures, and chronic anemia and thrombocytopenia.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH16 is an autosomal recessive, severe form characterized by hypotonia and severe global developmental delay apparent from early infancy. Other features may include stereotypic movements, spasticity, and progressive microcephaly.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH17 is an autosomal recessive, severe form clinically characterized by neonatal hypotonia, feeding and respiratory difficulties, central apnea, and bradycardia. Most affected individuals die in infancy. Brain imaging shows cerebellar and brainstem hypoplasia.
Pontocerebellar hypoplasia with anterior horn cell disease
Pontocerebellar hypoplasia with infantile spinal muscular atrophy
A disorder characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth.
A severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement.
A severe autosomal recessive neurodegenerative disease characterized by cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system, and spinal motor neuron disease. Affected individuals manifest failure to thrive, severe muscle weakness, spasticity and psychomotor retardation. Vision and hearing are impaired.
An autosomal recessive neurologic disorder with onset at birth or in infancy, and characterized by progressive axonal motor neuronopathy, severe generalized hypotonia, respiratory insufficiency, and cerebellar atrophy. Death in childhood may occur.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1E is an autosomal recessive form characterized by severe hypotonia and respiratory insufficiency apparent soon after birth. Additional features may include optic atrophy, peripheral neuropathy, dysmorphic features, congenital contracture or foot deformities, and seizures. Death occurs in the first days or weeks of life. Postmortem brain imaging show pontocerebellar atrophy and loss of anterior motor neurons in the spinal cord.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1F is an autosomal recessive form characterized by hypotonia, global developmental delay, poor overall growth, and dysmorphic facial features. Brain imaging shows pontocerebellar hypoplasia, thin corpus callosum, cerebral atrophy, and delayed myelination.
Pontocerebellar hypoplasia with progressive cerebral atrophy
A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration.
A disorder characterized by postnatal onset of progressive atrophy of the cerebrum and cerebellum, microcephaly, profound intellectual disability, spasticity, and variable seizures.
Progressive cerebello-cerebral atrophy type 2
An autosomal recessive neurodegenerative disorder characterized by progressive cerebello-cerebral atrophy, profound intellectual disability, progressive microcephaly, spasticity, and early-onset epilepsy.
A neurodevelopmental disorder characterized by progressive microcephaly, cognitive and motor delay, poor or absent speech, seizures, and spasticity. PCH2F inheritance is autosomal recessive.
Cerebellar atrophy with progressive microcephaly
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum. Brain MRI shows an abnormally small cerebellum and brainstem, decreased cerebral white matter, and a thin corpus callosum. PCH3 features include seizures, short stature, optic atrophy, progressive microcephaly, severe developmental delay.
Encephalopathy fatal infantile with olivopontocerebellar hypoplasia
A disorder characterized by an abnormally small cerebellum and brainstem, severe neonatal encephalopathy, microcephaly, myoclonus and muscular hypertonia. There is a severe inferior olivary and pontine neuronal loss and a diffuse white matter gliosis.
Olivopontocerebellar hypoplasia, fetal-onset
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum. Brain MRI shows an abnormally small cerebellum and brainstem, decreased cerebral white matter, and a thin corpus callosum.
Fatal infantile encephalopathy with mitochondrial respiratory chain defects
A disorder characterized by an abnormally small cerebellum and brainstem, infantile encephalopathy, generalized hypotonia, lethargy and poor feeding. Recurrent apnea, intractable seizures occur early in the course of this condition.
A form of pontocerebellar hypoplasia, a group of related disorders characterized by underdevelopment of the pons and the cerebellum. Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size. PCH7 patients manifest delayed psychomotor development, hypotonia, breathing abnormalities, and gonadal abnormalities.
An autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum.
A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH9 features include severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination.
Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal
An autosomal recessive multisystem disorder with onset in utero and death in the neonatal period. Affected infants show respiratory insufficiency and almost no spontaneous movement at birth. Additional features include corneal clouding, seizures, dysmorphic facies, contractures, and progressive pontocerebellar hypoplasia with simplified gyral pattern and white matter abnormalities. Some patients may have cardiac anomalies or cardiac hypertrophy.
Cleft lip/palate, paramedian mucous cysts of the lower lip, popliteal pterygium, digital and genital anomalies
An autosomal dominant disorder characterized by oro-facial, skin and genital anomalies. Expressivity is variable. Clinical features include cleft lip/palate, lower lip cysts, syngnathia, congenital ankyloblepharon filiforme in some cases, bifid scrotum, hypoplastic scrotum, hypoplastic uterus, talipes equinovarus.
An autosomal recessive disorder characterized by cerebellar dysplasia, cerebellar vermis atrophy, cerebellar cysts in most patients, high myopia, variable retinal dystrophy, and eye movement abnormalities including strabismus, ocular apraxia, nystagmus. Affected individuals have ataxia, delayed motor development, language impairment, and intellectual disability with variable severity.
A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported.
Disseminated superficial actinic porokeratosis 1
Porokeratosis, disseminated superficial actinic, 1
Porokeratosis 3, disseminated superficial actinic type
Porokeratosis 7, disseminated superficial actinic type
Porokeratosis 8, disseminated superficial actinic type
A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life.
An autosomal recessive disorder characterized by portal hypertension associated with hepatosplenomegaly, in absence of cirrhosis, extrahepatic diseases, and splanchnic venous thrombosis. Portal hypertension is defined by a portal venous system pressure that is at least 5 mm Hg higher than the pressure in the inferior vena cava. High pressure in the portal venous system leads to shunting of blood through vessels that are poorly suited to carrying large blood volumes, resulting in collateral circulation and splenomegaly. NCPH1 patients show normal liver function.
An autosomal recessive disorder characterized by portal hypertension associated with hepatosplenomegaly, in absence of cirrhosis. Portal hypertension is defined by a portal venous system pressure that is at least 5 mm Hg higher than the pressure in the inferior vena cava. High pressure in the portal venous system leads to shunting of blood through vessels that are poorly suited to carrying large blood volumes, resulting in collateral circulation and splenomegaly. NCPH2 patients have jaundice, hyperbilirubinemia, pancytopenia, including neutropenia, lymphopenia, and thrombocytopenia, hepatosplenomegaly, and esophageal varices. Some patients may have recurrent infections or features suggestive of an immunodeficiency.
POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.
Posterior column ataxia with retinitis pigmentosa
A neurodegenerative syndrome beginning in infancy with areflexia and retinitis pigmentosa. Nyctalopia (night blindness) and peripheral visual field loss are usually evident during late childhood or teenage years, with subsequent progressive constriction of the visual fields and loss of central retinal function over time. A sensory ataxia caused by degeneration of the posterior columns of the spinal cord results in a loss of proprioceptive sensation that is clinically evident in the second decade of life and gradually progresses. Scoliosis, camptodactyly, achalasia, gastrointestinal dysmotility, and a sensory peripheral neuropathy are variable features of the disease. Affected individuals have no clinical or radiological evidence of cerebral or cerebellar involvement.
A syndrome characterized by foramina parietalia permagna, multiple exostoses, and craniofacial dysostosis, and intellectual disability in some cases.
A hypertensive disorder of pregnancy characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks' gestation with clinically relevant proteinuria. It impacts 2 individuals, the mother and her child, both of whom can be severely affected. Preeclampsia is one of the causes of maternal mortality and morbidity worldwide.
Polydactyly consists of duplication of the distal phalanx. The thumb in PPD2 is usually opposable and possesses a normal metacarpal.
A condition defined as the development of secondary sexual characteristics in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of puberty in the population. Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis.
A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.
A rare cause of female primary infertility. In affected women, ovulation proceeds normally and the retrieved oocytes appear normal, but zygote formation and division are severely impaired. Inheritance is autosomal recessive.
A rare cause of female primary infertility. In affected women, ovulation and fertilization proceed normally but embryos are arrested at early stages of development. Inheritance is autosomal recessive.
An autosomal recessive condition characterized by a clotting defect due to prolongation of activated partial thromboplastin time. Affected individuals are clinically asymptomatic.
Premature aging syndrome, Penttinen type
A syndrome characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis.
Consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant.
Hypergonadotropic ovarian failure X-linked
An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
An autosomal dominant form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.
A form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. POF17 transmission pattern is consistent with autosomal recessive inheritance.
A form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. POF18 is an autosomal recessive form characterized by irregular menstrual cycles and cessation of menstruation in the third decade of life. The uterus is small, ovaries may be small or rudimentary, and do not show follicular activity.
A form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. POF19 is an autosomal recessive form characterized by irregular menstrual cycles and cessation of menstruation in the third decade of life.
A form of premature ovarian failure, an ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. POF20 inheritance is autosomal recessive.
Primary aldosteronism, seizures, and neurologic abnormalities
A disorder characterized by hypertension, hypokalemia, and high aldosterone levels with low plasma renin activity and an elevated aldosterone/renin ratio. Other features include generalized seizures, cerebral palsy, spasticity, intellectual disability, and developmental delay.
Autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands.
Familial posterior openbite malocclusion
Non-syndromic primary failure of eruption
Rare condition that has high penetrance and variable expressivity and in which tooth retention occurs without evidence of any obvious mechanical interference. Instead, malfunction of the eruptive mechanism itself appears to cause nonankylosed permanent teeth to fail to erupt, although the eruption pathway has been cleared by bone resorption.
Primary pigmented nodular adrenocortical disease 1
Primary pigmented micronodular adrenocortical disease 1
Primary pigmented nodular adrenocortical disease-1
A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. PPNAD1 is most often diagnosed in patients with Carney complex, a multiple neoplasia syndrome. However it can also be observed in patients without other manifestations.
Primary pigmented nodular adrenocortical disease 2
Primary pigmented micronodular adrenocortical disease 2
Primary pigmented nodular adrenocortical disease-2
A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
Primary pigmented nodular adrenocortical disease 3
Primary pigmented nodular adrenocortical disease 4
Condition in which air is present in the pleural space in the absence of a precipitating event, such as trauma or lung disease. This results in secondary collapse of the lung, either partially or completely, and some degree of hypoxia. PSP is relatively common, with an incidence between 7.4-18/100'000 for men and 1.2-6/100'000 for women and a dose-dependent, increased risk among smokers. Most cases are sporadic, typically occurring in tall, thin men aged 10-30 years and generally while at rest. Familial PSP is rarer and usually is inherited as an autosomal dominant condition with reduced penetrance, although X-linked recessive and autosomal recessive inheritance have also been suggested.
Primordial dwarfism-immunodeficiency-lipodystrophy syndrome
An autosomal recessive syndrome characterized by growth failure with in utero growth retardation and severe postnatal growth restriction, severe microcephaly, absence of subcutaneous fat, and significant haematological and immune dysfunction. Patients have hypo- or agammaglobulinemia, lymphopenia, anemia, and thrombocytopenia. Most affected individuals die in early childhood from either respiratory or gastrointestinal infections.
Ossified ear cartilages with mental deficiency, muscle wasting, and bony changes
A disease characterized by macrocephaly, intellectual disability, disturbed behavior, dysmorphic facial features, ectopic calcifications, large calcified ear auricles, and progressive muscle wasting.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1
Chronic progressive external ophthalmoplegia
Progressive external ophthalmoplegia autosomal dominant
A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2
Progressive external ophthalmoplegia autosomal dominant 2
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3
Progressive external ophthalmoplegia autosomal dominant 3
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 4
Progressive external ophthalmoplegia autosomal dominant 4
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5
Progressive external ophthalmoplegia autosomal dominant 5
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6
Progressive external ophthalmoplegia autosomal dominant 6
A disorder characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2
A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB2 patients manifest exercise intolerance, muscle weakness, and signs and symptoms of spinocerebellar ataxia, such as impaired gait and dysarthria. Some patients may have respiratory insufficiency.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
Progressive external ophthalmoplegia, autosomal recessive 3
A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB3 patients manifest adult-onset progressive external ophthalmoplegia and progressive proximal muscle weakness associated with muscle atrophy.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4
Progressive external ophthalmoplegia, autosomal recessive 4
A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB4 patients manifest clinically variable features including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis, and adult-onset lower motor neuron syndrome with mild cognitive impairment.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5
Progressive external ophthalmoplegia, autosomal recessive 5
A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB5 features include slowly progressive ptosis, intermittent double vision, cardiac arrhythmias, exercise intolerance, proximal limb and neck muscle weakness, and cerebellar ataxia. Patients skeletal muscle biopsy show numerous COX-deficient ragged-red fibers, increased mtDNA deletions, and extensive variable mtDNA rearrangements.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive, 1
Progressive external ophthalmoplegia autosomal recessive
A severe form of progressive external ophthalmoplegia, a disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. It is clinically more heterogeneous than the autosomal dominant forms.
Progressive familial heart block type IA
A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death.
Progressive familial heart block type IB
Rare autosomal dominant disorder characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue.
Arthropathy, progressive pseudorheumatoid, of childhood
Progressive pseudorheumatoid arthropathy of childhood
Spondyloepiphyseal dysplasia tarda with progressive arthropathy;
An autosomal recessive disorder characterized by stiffness and swelling of joints, motor weakness and joint contractures. Signs and symptoms of the disease develop typically between three and eight years of age. This progressive disease is a primary disorder of articular cartilage with continued cartilage loss and destructive bone changes with aging.
Characterized by akinetic-rigid syndrome, supranuclear gaze palsy, pyramidal tract dysfunction, pseudobulbar signs and cognitive capacities deterioration. Neurofibrillary tangles and gliosis but no amyloid plaques are found in diseased brains. Most cases appear to be sporadic, with a significant association with a common haplotype including the MAPT gene and the flanking regions. Familial cases show an autosomal dominant pattern of transmission with incomplete penetrance; genetic analysis of a few cases showed the occurrence of tau mutations, including a deletion of Asn-613.
Progressive symmetric erythrokeratodermia
Erythrokeratodermas are a group of disorders characterized by widespread erythematous plaques, either stationary or migratory, associated with features that include palmoplantar keratoderma. PSEK is characterized by erythematous and hyperkeratotic plaques.
A multisystem disorder associated with massive iminodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. Clinical features include skin ulcers, developmental delay, recurrent infections, and a characteristic facies.
Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome
Cerebral proliferative glomeruloid vasculopathy
Encephaloclastic proliferative vasculopathy
Hydrocephaly/hydranencephaly due to cerebral vasculopathy
A rare prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. Hydranencephaly is a condition where the greater portions of the cerebral hemispheres and corpus striatum are replaced by cerebrospinal fluid and glial tissue.
Prolonged electroretinal response suppression
Characterized by difficulty adjusting to sudden changes in luminance levels mediated by cones.
Results in higher susceptibility to bacterial infections; especially to meningococcal infections. Three phenotypes have been reported: complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin (type III).
Life-threatening disease characterized by episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental retardation, and intolerance to protein.
Characterized by obesity, hypogonadism, hypoadrenalism, reactive hypoglycemia as well as marked small-intestinal absorptive dysfunction It is due to impaired processing of prohormones.
A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
Proteasome-associated autoinflammatory syndrome 1
Autoinflammation, lipodystrophy, and dermatosis syndrome
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome
Joint contractures muscular atrophy microcytic anemia and panniculitis-induced lipodystrophy
Secondary hypertrophic osteoperiostosis with pernio
An autosomal recessive autoinflammatory disorder characterized by early childhood onset of recurrent fever, joint stiffness and severe contractures of the hands and feet, and erythematous skin lesions with subsequent development of lipodystrophy and laboratory evidence of immune dysregulation. Accompanying features may include muscle weakness and atrophy, hepatosplenomegaly, and microcytic anemia.
Proteasome-associated autoinflammatory syndrome 2
An autosomal dominant autoinflammatory disorder characterized by onset in early infancy and severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency.
Proteasome-associated autoinflammatory syndrome 3
Proteasome-associated autoinflammatory syndrome 3, digenic
An autoinflammatory disorder characterized by onset in early infancy and recurrent fever, nodular dermatitis, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and immune dysregulation. Variable accompanying features may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications. PRAAS3 inheritance is autosomal recessive or digenic.
Proteasome-associated autoinflammatory syndrome 4
An autosomal recessive, autoinflammatory disorder characterized by panniculitis and erythematous skin lesions apparent in early infancy. Additional features include hepatosplenomegaly, lymphadenopathy, autoimmune hemolytic anemia, fever, generalized lipodystrophy, myositis, joint contractures, and mild motor and speech delay.
Proteasome-associated autoinflammatory syndrome 5
An autosomal recessive, autoinflammatory disorder characterized by recurrent, polymorphic disseminated cutaneous rash with annular lesions, non-specific lymphocytic infiltration in the skin, fever, failure to thrive, and persistent hepatosplenomegaly. Disease onset is in early infancy.
An autosomal recessive condition characterized by isolated, non-progressive proteinuria in absence of renal disease and hypertension. Onset of proteinuria is in the first decade of life.
Partial gigantism of hands and feet nevi hemihypertrophy and macrocephaly
A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes.
An autosomal recessive form of porphyria with onset usually before age 10 years. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.
An autosomal dominant form of porphyria with onset in infancy. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.
Absence of abdominal muscles with urinary tract abnormality and cryptorchidism
A syndrome characterized by thin abdominal musculature with overlying lax skin, cryptorchism, megacystis with disorganized detrusor muscle, and urinary tract abnormalities.
Band-like calcification with simplified gyration and polymicrogyria
An autosomal recessive neurologic disorder with characteristic clinical and neuroradiologic features that mimic intrauterine TORCH infection in the absence of evidence of infection. Affected individuals have congenital microcephaly, intracranial calcifications, and severe developmental delay.
An autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent.
An autosomal recessive disorder characterized by developmental delay with acute episodes of fever and multisystemic organ involvement, including coagulopathy, elevated liver enzymes, and proteinuria, often associated with thrombotic microangiopathy. Brain imaging shows progressive intracranial calcifications, white matter abnormalities, and sometimes cerebral or cerebellar atrophy. Disease onset is in the neonatal period, and death in early childhood is common.
A bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by the platelet glycoprotein Ib (GP Ib) receptor complex. Hemostatic function is impaired due to the removal of VWF multimers from the circulation.
Spondyloepiphyseal dysplasia pseudoachondroplastic
A skeletal dysplasia usually manifesting in the second year of life and characterized by moderate to severe disproportionate short stature, deformity of the lower limbs, brachydactyly, ligamentous laxity, and degenerative joint disease.
A common hair disorder characterized by a pustular foreign body inflammatory reaction that is induced by ingrown hairs of the facial and submental (barbea) regions after regular shaving. It primarily affects curly haired males. The etiology of PFB is multifactorial.
Pseudohyperkalemia, familial, 2, due to red cell leak
A dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape.
Pseudohypoaldosteronism 1, autosomal dominant
Pseudohypoaldosteronism type I, autosomal dominant
A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.
Pseudohypoaldosteronism 1B1, autosomal recessive
Pseudohypoaldosteronism type I, autosomal recessive
A form of pseudohypoaldosteronism type 1, a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. The disorder affects multiple organs, and is characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss.
Pseudohypoaldosteronism 1B2, autosomal recessive
Pseudohypoaldosteronism, type IB2, autosomal recessive
Pseudohypoaldosteronism 1B3, autosomal recessive
Pseudohypoaldosteronism, type IB3, autosomal recessive
An autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.
An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics.
A disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive.
An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.
Albright hereditary osteodystrophy with multiple hormone resistance
A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.
A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH.
Pseudovaginal perineoscrotal hypospadias
Familial incomplete male pseudohermaphroditism type 2
Male pseudohermaphroditism due to 5-alpha-reductase deficiency
A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum.
A multisystem disorder characterized by accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Burch membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d'orange, angioid streaks, and choroidal neovascularizations, of the skin including soft, ivory colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings.
Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency
PXE-like disorder with multiple coagulation factor deficiency
Characterized by hyperlaxity of the skin involving the entire body. Important phenotypic differences with classical PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization are slightly different from those in classic PXE.
A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
Interleukin 36 receptor antagonist deficiency
A life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein.
A form of pustular psoriasis, a life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein.
An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).
Rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. Most patients are asymptomatic for several years or even for decades and generally, the diagnosis is incidental to clinical investigations unrelated to the disease. Cases with early-onset or rapid progression are rare. A 'sandstorm-appearing' chest roentgenogram is a typical diagnostic finding. The onset of this potentially lethal disease varies from the neonatal period to old age and the disease follows a long-term, progressive course, resulting in a slow deterioration of lung functions. Pulmonary alveolar microlithiasis is a recessive monogenic disease with full penetrance.
Severe early-onset chronic obstructive pulmonary disease
A common, complex disorder defined by irreversible airflow obstruction due to chronic bronchitis, emphysema, and/or small airways disease. Airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC).
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1
An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length.
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 3
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 4
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 5
A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. PFBMFT5 inheritance is autosomal dominant.
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 6
A disease characterized by elevated pulmonary artery pressure. Pulmonary hypertension in the neonate is associated with multiple underlying problems such as respiratory distress syndrome, meconium aspiration syndrome, congenital diaphragmatic hernia, bronchopulmonary dysplasia, sepsis, or congenital heart disease.
A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
A form of primary pulmonary hypertension, a disease defined by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. Primary pulmonary hypertension exhibits incomplete penetrance, sex bias and variable age of onset, both within and between families. PPH5 is an autosomal recessive form characterized by the onset in infancy. Death in early childhood is common.
Pulmonary surfactant metabolism dysfunction 1
Congenital pulmonary alveolar proteinosis 1
Interstitial lung disease due to surfactant protein B deficiency
Interstitial lung disease non-specific due to surfactant protein B deficiency
A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.
Pulmonary surfactant metabolism dysfunction 2
Congenital pulmonary alveolar proteinosis 2
Desquamative interstitial pneumonitis due to surfactant protein C deficiency
Interstitial lung disease due to surfactant protein C deficiency
A rare disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course, due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.
Pulmonary surfactant metabolism dysfunction 3
Congenital pulmonary alveolar proteinosis 3
Interstitial lung disease due to ABCA3 deficiency
Pulmonary surfactant metabolism dysfunction 4
Congenital pulmonary alveolar proteinosis 4
Pulmonary surfactant metabolism dysfunction 5
Pulmonary venoocclusive disease 1, autosomal dominant
A disease characterized by widespread fibrous obstruction and intimal thickening of septal veins and preseptal venules, a low diffusing capacity for carbon monoxide, occult alveolar hemorrhage, and nodular ground-glass opacities, septal lines and lymph node enlargement showed by high-resolution computed tomography of the chest. It is frequently associated with pulmonary capillary dilatation and proliferation, and is a rare and devastating cause of pulmonary hypertension.
Pulmonary venoocclusive disease 2, autosomal recessive
Familial pulmonary capillary hemangiomatosis
Purine nucleoside phosphorylase deficiency
Immunodeficiency due to purine nucleoside phosphorylase deficiency
A disorder that interrupts both the catabolism of inosine into hypoxanthine and guanosine into guanine, and leads to the accumulation of guanosine, inosine, and their deoxified by-products. The main clinical presentation is recurrent infections due to severe T-cell immunodeficiency. Some patients also have neurologic impairment.
A rare autosomal recessive bone disorder characterized by deformity of the skull, maxilla and phalanges, osteosclerosis, and fragility of bone.
A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures.
Pyridoxine-5'-phosphate oxidase deficiency
PNPO-related neonatal epileptic encephalopathy
Seizures, pyridoxine-resistant, PLP-sensitive
The main feature of neonatal epileptic encephalopathy is the onset within hours of birth of a severe seizure disorder that does not respond to anticonvulsant drugs and can be fatal. Seizures can cease with the administration of PLP, being resistant to treatment with pyridoxine,.
Characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride.
Pyrin-associated autoinflammatory disease
An autosomal dominant autoinflammatory disorder characterized by childhood onset of recurrent episodes of fever, neutrophilic dermatosis, myalgia and arthralgia. The neutrophilic dermatosis comprises a spectrum of clinical manifestations, including severe acne, sterile skin abscesses, pyoderma gangrenosum, and neutrophilic small-vessel vasculitis. Pathological examination of affected skin shows a dense, predominantly neutrophilic, vascular, perivascular, and interstitial infiltrate. PAAND has incomplete penetrance and variable expressivity.
Leads to lactic acidosis, intellectual disability and death. It occurs in three forms: mild or type A, severe neonatal or type B, and a very mild lacticacidemia.
Pyruvate dehydrogenase E1-alpha deficiency
Ataxia intermittent with abnormal pyruvate metabolism
Ataxia intermittent with pyruvate dehydrogenase or decarboxylase deficiency
An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis.
Pyruvate dehydrogenase E1-beta deficiency
Lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex
Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. In this form of PDH deficiency episodic dystonia is the major neurological manifestation, with other more common features of pyruvate dehydrogenase deficiency, such as hypotonia and ataxia, being less prominent.
Pyruvate dehydrogenase E3-binding protein deficiency
Lactic acidemia due to defect in lipoyl-containing component X of the pyruvate dehydrogenase complex
A metabolic disorder characterized by decreased activity of the pyruvate dehydrogenase complex without observable reduction in the activities of enzymes E1, E2, or E3. Clinical features include hypotonia and psychomotor retardation.
Pyruvate dehydrogenase phosphatase deficiency
Results in lactic acidosis leading to neurological dysfunction.
Hemolytic anemia due to red cell pyruvate kinase deficiency
Hereditary non-spherocytic hemolytic anemia due to pyruvate kinase deficiency
Pyruvate kinase deficiency of erythrocyte
Pyruvate kinase-deficient hemolytic anemia
A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.
Autosomal dominant phenotype characterized by increase of red blood cell ATP.
An autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.
An auricular abnormality characterized by a cleft between the lobule and the lower part of the helix, sometimes accompanied by a prominent or deficient upper part of the helix, shallow skin dimple on the posterior surface of the ear, or transposition of the ear lobe/antitragus.
An autosomal dominant neurodevelopmental disorder characterized by severely impaired global development, intellectual disability, microcephaly, facial dysmorphism, and variable congenital anomalies affecting the skeletal, genitourinary, cardiac, and other organ systems.
Severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive.
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, hypotonia, mild motor difficulties, impaired intellectual development, speech delay, craniofacial dysmorphism, and variable behavioral abnormalities.
Radiohumeral fusions with other skeletal and craniofacial anomalies
Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies
A disease characterized by craniofacial malformations, occipital encephalocele, radiohumeral fusions, oligodactyly, advanced osseous maturation, and calvarial mineralization defects.
Radioulnar synostosis with amegakaryocytic thrombocytopenia 1
Radio-ulnar synostosis with amegakaryocytic thrombocytopenia
Thrombocytopenia, congenital, with radioulnar synostosis
The syndrome consists of an unusual association of bone marrow failure and skeletal defects. Patients have the same skeletal defects, the proximal fusion of the radius and ulna, resulting in extremely limited pronation and supination of the forearm. Some patients have also symptomatic thrombocytopenia, with bruising and bleeding problems since birth, necessitating correction by bone marrow or umbilical-cord stem-cell transplantation.
Radioulnar synostosis with amegakaryocytic thrombocytopenia 2
Radioulnar synostosis and amegakaryocytic thrombocytopenia 2
An autosomal dominant disease characterized by proximal fusion of the radius and ulna resulting in extremely limited pronation and supination of the forearm, and congenital thrombocytopenia that progresses to pancytopenia.
An autosomal dominant disease characterized by proximal fusion of the radius and ulna resulting in extremely limited pronation and supination of the forearm. There are two disease forms. Radioulnar synostosis type 1 is characterized by a proximal fusion between the radius and ulna, and the radial head is absent. Radioulnar synostosis type 2 is characterized by a fusion just distal to the proximal radial epiphysis, and congenital dislocation of the radial head. In radioulnar synostosis type 2 there is also a restriction of extension at the elbow.
An autosomal recessive disorder characterized by variably impaired intellectual and motor development, a characteristic facial dysmorphism, truncal obesity, and hypotonia. The facial dysmorphism comprises prominent eyebrows with lateral thinning, downward-slanting palpebral fissures, bulbous tip of the nose, large ears, and a thin upper lip. Behavioral problems, including overeating, verbal and physical aggression, have been reported in some cases. Serum transferrin isoelectric focusing shows a type 2 pattern.
An autosomal dominant syndrome characterized by intellectual disability and overgrowth manifesting as increased birth length, height, weight, and/or head circumference.
Osteomalacia, sclerosing, with cerebral calcification
An autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome, although some patients survive into childhood. Clinical features include generalized increase in the density of all bones and a marked increase in the ossification of the skull, craniofacial dysplasia and microcephaly.
Rajab interstitial lung disease with brain calcifications 1
Developmental delay, small stature, microcephaly, and brain calcifications
Neurodevelopmental disorder with brain, liver, and lung abnormalities
An autosomal recessive, lethal neurodevelopmental disorder characterized by multiple clinical manifestations including intrauterine growth restriction, failure to thrive, developmental delay, hypotonia, interstitial lung disease, and liver dysfunction. Brain imaging shows abnormal periventricular white matter, basal ganglia echogenicity, cerebral volume loss, incomplete closure of the Sylvian fissures, and normal myelination.
Rajab interstitial lung disease with brain calcifications 2
An autosomal recessive disorder characterized by interstitial lung disease, growth delay, hypotonia, liver disease, and brain abnormalities including diffuse, symmetrical brain calcifications and periventricular cysts.
Disease characterized by radial and patellar aplasia or hypoplasia.
Anhidrotic ectodermal dysplasia with cleft lip/palate
A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate. RHS inheritance is autosomal dominant.
RAS-associated autoimmune leukoproliferative disorder
Autoimmune lymphoproliferative syndrome, type IV
Autoimmune lymphoproliferative syndrome 4
A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.
An autosomal dominant disorder characterized by poor pre- and postnatal growth, facial dysmorphism, and variable developmental delay with delayed motor and speech acquisition and impaired intellectual. Other features may include hypotonia and behavioral abnormalities.
An X-linked syndrome characterized by borderline to severe intellectual disability and impaired language development. Additional features include behavioral problems, psychiatric disorders, seizures, progressive ataxia, brain abnormalities, and facial dysmorphisms.
Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion of myoglobin in the urine.
Reducing body myopathy, X-linked 1A, severe, with infantile or early childhood onset
Myopathy, reducing body, X-linked, early-onset, severe
A rare myopathy clinically characterized by rapidly progressive muscular weakness, and pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase in the absence of substrate, alpha-glycerophosphate. The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. Death in childhood is frequent in the severe form of the disease, due to respiratory failure.
Reducing body myopathy, X-linked 1B, with late childhood or adult onset
A rare myopathy clinically characterized by rapidly progressive muscular weakness, and pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase in the absence of substrate, alpha-glycerophosphate. The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies.
Hereditary motor and sensory neuropathy IV
A rare autosomal recessive peroxisomal disorder characterized by the accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Cardinal clinical features are retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Half of all patients exhibit generalized, mild to moderate ichthyosis resembling ichthyosis vulgaris. Less constant features are nerve deafness, anosmia, skeletal abnormalities, cataracts and cardiac impairment.
Form of chronic hemolytic anemia in which the red blood cells have a stomatocytosis and spherocytosis morphology, an increased osmotic fragility, an altered ion transport system, and abnormal membrane phospholipid organization.
Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype.
A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium.
Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. RCCX1 histology shows both clear cells and papillary architecture, often with abundant psammoma bodies, although variable histologic features have been observed.
Atypical familial juvenile hyperuricemic nephropathy
Congenital anomalies of the kidney and urinary tract with diabetes
Familial hypoplastic glomerulocystic kidney
Glomerulocystic kidney disease hypoplastic type
Maturity-onset diabetes of the young type 5
Tubulointerstitial kidney disease, autosomal dominant, 3
An autosomal dominant disorder comprising non-diabetic renal disease resulting from abnormal renal development, and diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY5). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelves, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Affected individuals may also have abnormalities of the genital tract.
An anomaly of the kidney characterized by numerous renal cysts and apparent disorder of differentiation of the renal parenchyma. Kidney of affected individuals lack the normal renal bean shape, and the collection drainage system. The cystic, dysplastic kidney contains undifferentiated mesenchyme, cartilaginous tissue, and immature collecting ducts.
A disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction.
A perinatally lethal renal disease encompassing a spectrum of kidney development defects, including renal agenesis, bilateral renal aplasia, hypoplasia, (cystic) dysplasia, and severe obstructive uropathy.
A severe, autosomal dominant disease encompassing a spectrum of kidney development defects. Clinical manifestations are highly variable and include bilateral or unilateral renal agenesis, renal aplasia, hypoplasia, (cystic) dysplasia, severe obstructive uropathy, and vesicoureteral reflux. Bilateral renal agenesis is almost invariably fatal in utero or in the perinatal period. Unilateral renal agenesis can lead to future health issues including end-stage renal disease.
An autosomal recessive, severe congenital anomaly of the kidney and urinary tract characterized by bilateral renal agenesis, and severely reduced or absent amniotic fluid during pregnancy. Patients exhibit the Potter sequence, including flattened nose, ear anomalies, and receding chin. Some affected individuals have limb contractures and joint dislocations. Bilateral renal agenesis is almost invariably fatal in utero or in the perinatal period.
An autosomal dominant disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification.
Renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss
Autosomal recessive renal tubular acidosis with progressive nerve deafness
Distal renal tubular acidosis with deafness
Renal tubular acidosis with progressive nerve deafness
An autosomal recessive disease characterized by the association of renal distal tubular acidosis with sensorineural hearing loss. Distal renal tubular acidosis is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification.
Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss
Distal renal tubular acidosis with late-onset sensorineural hearing loss
Distal renal tubular acidosis with preserved hearing
An autosomal recessive disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification.
Renal tubular acidosis, distal, 4, with hemolytic anemia
Autosomal recessive distal RTA with hemolytic anemia
An autosomal recessive disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis.
Renal tubular acidosis, distal, with normal red cell morphology
A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification.
Renal tubular acidosis, proximal, with ocular abnormalities and impaired intellectual development
Proximal renal tubular acidosis with ocular abnormalities
An extremely rare autosomal recessive syndrome characterized by short stature, profound proximal renal tubular acidosis, intellectual disability, bilateral glaucoma, cataracts and bandkeratopathy. pRTA is due to a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia.
Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
A disease characterized by cystic malformations of the kidneys, liver, and pancreas. The pathological findings consist of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates.
A form of renal-hepatic-pancreatic dysplasia, a disease characterized by cystic malformations of the kidneys, liver, and pancreas. The pathological findings consist of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates.
An X-linked syndrome characterized by intellectual disability, microcephaly, short stature, and small testes. The craniofacies tends to be narrow and tall with upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies.
Respiratory distress syndrome in premature infants
A lung disease affecting usually premature newborn infants. It is characterized by deficient gas exchange, diffuse atelectasis, high-permeability lung edema and fibrin-rich alveolar deposits called 'hyaline membranes'.
Respiratory papillomatosis, juvenile recurrent, congenital
An autosomal recessive disease characterized by recurrent growth of papillomas in the respiratory tract, and onset in early childhood. Papillomas are most commonly found in the larynx but may occur anywhere from the mouth to the bronchi. Children typically present within the first years of life with hoarseness or, in more severe cases, respiratory distress or stridor and airway obstruction. JRRP is associated with infection of the upper airway by human papillomaviruses of the alpha genus. The infection is thought to occur by vertical transmission at birth.
A neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation. The majority of patients also have periodic limb movements in sleep, which are characterized by involuntary, highly stereotypical, regularly occurring limb movements that occur during sleep.
Fetal hypokinesia sequence due to restrictive dermopathy
An autosomal recessive form of restrictive dermopathy, a genodermatosis mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial dysmorphism, sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life.
An autosomal dominant form of restrictive dermopathy, a genodermatosis mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial dysmorphism, sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life.
Severe combined immunodeficiency with leukopenia
A fatal form of severe combined immunodeficiency, characterized by absence of granulocytes, almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immunity, leading to fatal septicemia within days after birth. In bone marrow of individuals with reticular dysgenesis, myeloid differentiation is blocked at the promyelocytic stage, whereas erythro- and megakaryocytic maturation is generally normal. Inheritance is autosomal recessive.
A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia.
Retinal arterial macroaneurysm with supravalvular pulmonic stenosis
An autosomal recessive condition characterized by the bilateral appearance of 'beading' along the major retinal arterial trunks, with the subsequent formation of macroaneurysms. Affected individuals also have supravalvular pulmonic stenosis, often requiring surgical correction.
Characterized by minimal symptoms except for slowly progressive reduction in visual acuity.
Retinal degeneration autosomal recessive clumped pigment type
A retinopathy characterized by night blindness since early childhood, consistent with a severe reduction in rod function. Color vision is normal although there is a relatively enhanced function of short-wavelength-sensitive cones in the macula. Signs of retinal degeneration and clusters of clumped pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium are present.
Retinal dystrophy and microvillus inclusion disease
An autosomal recessive disease characterized by early-onset, severe retinal dystrophy associated with intractable congenital diarrhea. Intestinal biopsies show loss of microvilli, microvillus inclusions, and accumulation of subapical vesicles in villus enterocytes.
A disease characterized by obesity, night blindness, decreased visual acuity, and electrophysiological features of a rod cone dystrophy.
Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities
An autosomal dominant retinal dystrophy characterized by inner retinal dysfunction in association with ganglion cell abnormalities. Clinical features include mild photophobia, progressive loss of central vision, night blindness, and hyperreflectivity of nerve and ganglion cell layers.
An autosomal recessive disorder characterized by progressive leukodystrophy associated with developmental delay, spastic paraparesis, ataxia, and retinal dystrophy. Patients may show facial dysmorphism. Laboratory investigations reveal an abnormal profile of very-long chain fatty acid in plasma.
Retinal dystrophy with or without extraocular anomalies
An autosomal recessive disease characterized by progressive retinal dystrophy, chorioretinal macular atrophy, reduced cone and rod responses on ERG, and decrease visual acuity. Extraocular anomalies are variably present in some patients and include pulmonary fibrosis, sensorineural hearing loss, and endocrine features such as goiter and primary ovarian insufficiency.
Retinal dystrophy with or without macular staphyloma
An ocular disorder characterized by decreased vision which worsen over time, and dystrophic changes in the retina, such as retinal pigment epithelium mottling and vessel narrowing. Macular staphyloma, without high myopia, is present in some patients.
Retinal dystrophy, early-onset, with or without pituitary dysfunction
An autosomal dominant ocular disease characterized by pattern dystrophy of the retinal pigment epithelium, and photoreceptor degeneration. Mild developmental anomalies include optic nerve head dysplasia, microcornea, and Rathke's cleft cyst. Some patients manifest pituitary dysfunction.
Retinal dystrophy, iris coloboma, and comedogenic acne syndrome
A disease characterized by retinal degeneration, ocular colobomas involving both the anterior and posterior segment, impaired night vision and loss of visual acuity. Additional characteristic features include developmental abnormalities and severe acne.
Retinal dystrophy, juvenile cataracts, and short stature syndrome
A disorder characterized by retinal dystrophy resulting in progressive decrease in visual acuity and difficulties with night vision in the first decade of life, development of juvenile cataracts, facial dysmorphism, psychomotor developmental delays, learning disabilities and short stature. Ophthalmological findings include salt-and-pepper retinopathy, attenuation of the arterioles, generalized rod-cone dysfunction, mottled macula at an early age, and peripapillary sparing of the retinal pigment epithelium.
Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome
Splenomegaly, cytopenia, and vision loss
An autosomal dominant disorder characterized by decreased vision associated with optic nerve edema, evident in childhood. Low-grade ocular inflammation is common in affected individuals. Later in childhood or the second decade of life, patients have increasing visual impairment, abnormal cone function and loss of rod function. By the third decade of life, visual acuity ranges from counting fingers to no light perception. Patients also show anhidrosis, splenomegaly, mild pancytopenia, and most experience headaches that may be migraine-like in nature.
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Retinitis pigmentosa with or without paraarteriolar preservation of retinal pigment epithelium
RP with or without preserved paraarteriole retinal pigment epithelium
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP12 is an autosomal recessive, severe form often manifesting in early childhood. Patients experiment progressive visual field loss with severe visual impairment before the age of twenty. Some patients have a preserved paraarteriolar retinal pigment epithelium (PPRPE) and hypermetropia.
Retinitis pigmentosa juvenile TULP1-related
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP19 is characterized by choroidal atrophy.
Choroidoretinal degeneration with retinal reflex in heterozygous women
An X-linked retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. In RP3, affected males have a severe phenotype, and carrier females show a wide spectrum of clinical features ranging from completely asymptomatic to severe retinitis pigmentosa. Heterozygous women can manifest a form of choroidoretinal degeneration which is distinguished from other types by the absence of visual defects in the presence of a brilliant, scintillating, golden-hued, patchy appearance most striking around the macula, called a tapetal-like retinal reflex.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP32 inheritance is autosomal recessive.
Retinal degeneration autosomal recessive prominin-related
Retinitis pigmentosa autosomal recessive IDH3B-related
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP53 inheritance is autosomal dominant or autosomal recessive.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP75 inheritance is autosomal recessive.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP76 inheritance is autosomal recessive.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP77 inheritance is autosomal recessive.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP78 inheritance is autosomal recessive.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP79 inheritance is autosomal dominant.
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP80 inheritance is autosomal recessive.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP81 inheritance is autosomal recessive.
Retinitis pigmentosa 82 with or without situs inversus
An autosomal recessive disorder characterized by variable association of retinitis pigmentosa with situs inversus. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Situs inversus is a congenital abnormality in which organs in the thorax and the abdomen are opposite to their normal positions due to lateral transposition.
An autosomal dominant form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP84 is an autosomal recessive, early onset form characterized by night blindness by age 4 and complete blindness by age 8. Funduscopy shows severely attenuated retinal vessels, severe macular atrophy, and prominent and deep macular colobomas lacking neuroretinal tissue.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP85 is an autosomal recessive form manifesting as early-onset progressive difficulty to adapt in dim light and gradually decreasing visual acuity in both eyes.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP86 is an autosomal recessive form.
Retinitis pigmentosa 87 with choroidal involvement
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP87 is an autosomal dominant form characterized by a slowly progressive visual disturbance accompanied by extensive choroid/retinal atrophy that mimics certain aspects of choroideremia. Disease severity and age of onset are variable, and some carriers are unaffected.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP88 is an autosomal recessive form.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP89 is an autosomal dominant form associated with features of ciliopathy, including postaxial polydactyly, and renal and hepatic disease.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP90 is an autosomal recessive form.
Macular dystrophy, benign concentric annular
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP91 is an autosomal dominant form with bone-spicule pigmentation, attenuation of retinal vessels, and optic disk pallor on funduscopy. Patients may also experience early macular involvement, with photophobia and reduced visual acuity, and some show a bull's eye pattern of macular atrophy.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP92 is an autosomal recessive, mild form with onset of night blindness and vision loss in the third to sixth decades of life.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP93 is an autosomal recessive, mild to moderate form, with onset in the second or third decade of life.
Retinitis pigmentosa 94, variable age at onset, autosomal recessive
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field.
A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. RP95 is an autosomal recessive form characterized by pale optic disks, attenuation of retinal vessels, and atrophy of the retinal pigment epithelium with bone-spicule pigmentation.
An autosomal dominant form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field.
Retinitis pigmentosa and erythrocytic microcytosis
An autosomal recessive disease characterized by retinitis pigmentosa, red blood cell microcytosis and anisocytosis with mild anemia.
Retinitis pigmentosa and sinorespiratory infections with or without deafness
X-linked retinitis pigmentosa with deafness and sinorespiratory infections
A disease characterized by the association primary ciliary dyskinesia features with retinitis pigmentosa. Some patients also manifest deafness.
Retinitis pigmentosa with or without skeletal anomalies
Metaphyseal chondrodysplasia with retinitis pigmentosa
An autosomal recessive disease characterized by retinal degeneration, brachydactyly, short stature, craniofacial dysmorphism, and neurologic defects. Retinal defects are consistent with retinitis pigmentosa in most patients. Neurologic manifestations include mild-to-moderate intellectual disability and psychomotor retardation.
A form of fleck retina disease characterized by aggregation of white flecks posteriorly in the retina, causing night blindness and delayed dark adaptation. It differs from fundus albipunctatus in being progressive and evolving to generalized atrophy of the retina.
A vitreo-retinal dystrophy characterized by macular pathology and by splitting of the superficial layer of the retina. Macular changes are present in almost all cases. In the fundi, radially oriented intraretinal foveomacular cysts are seen in a spoke-wheel configuration, with the absence of foveal reflex in most cases. In addition, approximately half of cases have bilateral peripheral retinoschisis in the inferotemporal part of the retina. Aside from the typical fundus appearance, strabismus, nystagmus, axial hyperopia, defective color vision and foveal ectopy can be present. The most important complications are vitreous hemorrhage, retinal detachment, and neovascular glaucoma.
Autism-dementia-ataxia-loss of purposeful hand use
An X-linked dominant neurodevelopmental disorder, and one of the most common causes of intellectual disability in females. Patients appear to develop normally until 6 to 18 months of age, then gradually lose speech and purposeful hand movements, and develop microcephaly, seizures, autism, ataxia, intellectual disability and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood.
A severe neurodevelopmental disorder with features of classic Rett syndrome but earlier onset in the first months of life. Clinical features include progressive microcephaly, hypotonia, irresponsiveness and irritability in the neonatal period, intellectual disability, psychomotor regression and stereotypical movements.
Primary biliary cirrhosis scleroderma Raynaud disease and telangiectasia
A syndrome specifically associating limited cutaneous systemic sclerosis and primary biliary cirrhosis. It is characterized by liver disease, telangiectasia, abrupt onset of digital paleness or cyanosis in response to cold exposure or stress (Raynaud phenomenon), and variable features of scleroderma. The liver disease is characterized by pruritis, jaundice, hepatomegaly, increased serum alkaline phosphatase and positive serum mitochondrial autoantibodies, all consistent with primary biliary cirrhosis.
An autosomal recessive condition characterized by red blood cells that lack all Rh antigens, have increased osmotic fragility, diminished lifespan, and show changes in morphology resulting in stomatocytosis. Rh-null individuals have mild to moderate hemolytic anemia. They are at risk of having adverse reactions in response to transfusion or pregnancy, because they may produce antibodies against several of the Rh antigens.
Rhabdoid tumor predisposition syndrome 1
A familial cancer syndrome predisposing to renal or extrarenal malignant rhabdoid tumors and to a variety of tumors of the central nervous system, including choroid plexus carcinoma, medulloblastoma, and central primitive neuroectodermal tumors. Rhabdoid tumors are the most aggressive and lethal malignancies occurring in early childhood.
Rhabdoid tumor predisposition syndrome 2
A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas.
Rhegmatogenous retinal detachment autosomal dominant
A eye disease that most frequently results from a break or tear in the retina that allows fluid from the vitreous humor to enter the potential space beneath the retina. It is often associated with pathologic myopia and in most cases leads to visual impairment or blindness if untreated.
An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.
Chondrodysplasia punctata, rhizomelic form
Rhizomelic chondrodysplasia punctata, type 1
A peroxisome biogenesis disorder. It is characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe intellectual disability with spasticity.
Chondrodysplasia punctata, rhizomelic, due to dihydroxyacetonephosphate acyltransferase deficiency
Dihydroxyacetonephosphate acyltransferase deficiency
Glyceronephosphate O-acyltransferase deficiency
Peroxisomal dihydroxyacetonephosphate acyltransferase deficiency
Rhizomelic chondrodysplasia punctata, type 2
A form of rhizomelic chondrodysplasia punctata, a disease characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe intellectual disability with spasticity.
Alkyldihydroxyacetonephosphate synthase deficiency
Alkylglycerone-phosphate synthase deficiency
Rhizomelic chondrodysplasia punctata, type 3
Rhizomelic chondrodysplasia punctata, type 5
An autosomal recessive skeletal dysplasia characterized by short stature, marked rhizomelic shortening of the limbs, platyspondyly, hip dysplasia, and large hands and feet relative to height.
Rhizomelic limb shortening with dysmorphic features
An autosomal recessive skeletal dysplasia characterized by rhizomelic shortening of limbs as well as variable dysmorphic features, including macrocephaly, short neck, micrognathia, mild proptosis, downslanting palpebral fissures, depressed or broad nasal bridge and long philtrum.
Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly
Pelger-Huet anomaly with mild skeletal anomalies
Regressive spondylometaphyseal dysplasia
A disease characterized by abnormal nuclear shape and chromatin organization in blood granulocytes, short stature, and mild skeletal anomalies. Initial skeletal features may improve with age.
An autosomal recessive syndrome characterized by gaze palsy, retinitis pigmentosa, sensorineural hearing loss, hypopituitarism, nephronophthisis, and skeletal dysplasia.
A disorder caused by a primary defect in riboflavin metabolism, or by dietary riboflavin deficiency. Riboflavin deficiency during pregnancy results in hypoglycemia, metabolic acidosis, dicarboxylic aciduria and elevated plasma acylcarnitine levels in the newborn. Treatment with oral riboflavin results in complete resolution of the clinical and biochemical findings.
An autosomal recessive inborn error of polyols metabolism characterized by highly elevated level of ribitol and arabitol in brain and body fluids. Clinical features include leukoencephalopathy, psychomotor retardation from early life, neurologic regression, and a mild sensorimotor neuropathy.
Robin sequence with cleft mandible and limb anomalies
A syndrome characterized by a unique pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of mandible, cleft palate/Robin sequence, absence of central lower incisors, minor ears anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability is also a common finding.
1-alpha 25-hydroxyvitamin D3 deficiency selective
25-hydroxycholecalciferol-1-hydroxylase deficiency
Pseudovitamin D-deficiency rickets type IA
A disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets.
25-hydroxyvitamimn D3 deficiency selective
Pseudovitamin D(3) deficiency rickets due to 25-hydroxylase deficiency
Selective 25-hydroxyvitamin D(3) deficiency
An autosomal recessive disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets. The patients sera have low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activity and low levels of 25-hydroxyvitamin D.
Generalized resistance to 1,25-dihydroxyvitamin D
Hypocalcemic vitamin D-resistant rickets
Vitamin D-dependent rickets type 2A with or without alopecia
Vitamin D-resistant rickets with end-organ unresponsiveness to 1,25-dihydroxycholecalciferol
A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.
Radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties
An autosomal recessive disorder characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature.
Heterotaxy, visceroatrial, autosomal recessive
A severe complex congenital heart defect resulting from embryonic disruption of proper left-right axis determination. RAI is usually characterized by complete atrioventricular septal defect with a common atrium and univentricular AV connection, total anomalous pulmonary drainage, and transposition or malposition of the great arteries. Affected individuals present at birth with severe cardiac failure. Other associated abnormalities include bilateral trilobed lungs, midline liver, and asplenia, as well as situs inversus affecting other organs.
Congenital merosin-positive muscular dystrophy with early spine rigidity
Congenital muscular dystrophy Eichsfeld type
Congenital muscular dystrophy merosin-positive with early spine rigidity
Desmin-related myopathy with Mallory bodies
Multiminicore disease severe classic form
A neuromuscular disorder characterized by poor axial muscle strength, scoliosis and neck weakness, and a variable degree of spinal rigidity. Early ventilatory insufficiency can lead to death by respiratory failure.
Rigidity and multifocal seizure syndrome, lethal neonatal
A lethal, neonatal, neurologic disorder characterized by episodic jerking that is apparent in utero, lack of psychomotor development, axial and limb rigidity, frequent multifocal seizures, and dysautonomia. At birth, affected individuals have small heads, overlapping cranial sutures, small or absent fontanels, and depressed frontal bones. Infants show poorly responsive focal jerks of the tongue, face and arms in a nearly continuous sequence throughout life.
An ocular disorder characterized by bilateral annular limbal dermoids (growths with a skin-like structure) with corneal and conjunctival extension.
Muscular dystrophy, limb-girdle, type 1C
A disorder characterized by mechanically triggered contractions of skeletal muscle. Mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers and cause visible ripples to move over the muscle. RMD2 inheritance is autosomal dominant or autosomal recessive.
Dandy-Walker-like malformation with atrioventricular septal defect
A developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay.
A form of Ritscher-Schinzel syndrome, a developmental malformation syndrome characterized by cerebellar brain malformations, congenital heart defects, and craniofacial abnormalities. RTSC2 is an X-linked recessive form characterized by intellectual disability associated with posterior fossa defects, cardiac malformations, and minor abnormalities of the face and distal extremities.
A form of Ritscher-Schinzel syndrome, a developmental malformation syndrome characterized by cerebellar brain malformations, congenital heart defects, and craniofacial abnormalities. RTSC3 is an autosomal recessive form. Affected individuals show cranio-cerebello-cardiac anomalies, coloboma, microphthalmia, chondrodysplasia punctata, complicated skeletal malformations, periventricular nodular heterotopia and proteinuria.
An autosomal dominant form of Ritscher-Schinzel syndrome, a developmental malformation syndrome characterized by cerebellar brain anomalies associated with global developmental delay and impaired intellectual development, congenital heart defects, and craniofacial abnormalities.
Long bone deficiencies associated with cleft lip-palate
An autosomal recessive disorder characterized by pre- and postnatal growth retardation, intellectual disability, microcephaly, bilateral cleft lip and cleft palate, and mesomelic symmetric limb reduction. Severely affected infants may be stillborn or die shortly after birth. Patient chromosomes have a lack of cohesion involving heterochromatic C-banding regions around centromeres and the heterochromatin regions on the 1, 9, 16, and Y chromosomes. These findings are referred to as premature centromere separation (PCS) and heterochromatin repulsion (HR), and they are important for the diagnosis of the syndrome.
Acral dysostosis with facial and genital abnormalities
A disease characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally milder in dominant cases.
A rare skeletal dysplasia syndrome characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, costovertebral segmentation defects, and renal anomalies.
A form of Robinow syndrome, a rare skeletal dysplasia syndrome characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, genital hypoplasia, renal anomalies, and costovertebral segmentation defects.
Costovertebral segmentation defect with mesomelia
Robinow syndrome autosomal recessive with aplasia/hypoplasia of phalanges and metacarpals/metatarsals
Robinow syndrome autosomal recessive with brachy-syn-polydactyly
A recessive form of Robinow syndrome, a disease characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally far more severe in recessive cases, particularly skeletal abnormalities. All patients with the recessive form suffer from vertebral segmentation abnormalities, resulting in scoliosis and chest deformities. Rib fusions are considered to be characteristic of the autosomal recessive form. Patients can also present brachydactyly, with extensive aplasia/hypoplasia of the phalanges and metacarpals/metatarsals, and brachy-syn-polydactyly of the hands and oligodactyly of the feet.
Acrocephalosyndactyly Robinow-Sorauf type
An autosomal dominant syndrome characterized by craniosynostosis, asymmetry of orbits, flat face, hypertelorism, a thin, long, and pointed nose, shallow orbits, strabismus, and broad great toes with a duplication of the distal phalanx. RSS is clinically similar to Saethre-Chotzen syndrome, with the most characteristic additional feature in Robinow-Sorauf syndrome being a bifid or partially duplicated hallux.
A rod-cone dystrophy reminiscent of retinitis punctata albescens but with a substantially lower age at onset and more-rapid and distinctive progression. Rod-cone dystrophies results from initial loss of rod photoreceptors, later followed by cone photoreceptors loss.
Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction
An autosomal recessive disease characterized by visual impairment due to rod-cone dystrophy, sensorineural hearing loss, and Fanconi-type renal dysfunction resulting in rickets-like skeletal changes. Death may occur in childhood or young adulthood due to renal failure. Disease onset is before age 5 years.
Combined immunodeficiency, facial dysmorphism, optic nerve atrophy, skeletal anomalies, and developmental delay
An autosomal recessive digenic disorder characterized by global developmental delay, variable neurologic features such as seizures and ataxia, optic atrophy, dysmorphic facial features, distal skeletal anomalies, and recurrent invasive infections due to combined immunodeficiency.
Characterized by utero-vaginal atresia in otherwise phenotypically normal female with a normal 46,XX karyotype. Anomalies of the genital tract range from upper vaginal atresia to total Muellerian agenesis with urinary tract abnormalities. It has an incidence of approximately 1 in 5'000 newborn girls.
Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, X-linked
A condition characterized by the association of rolandic seizures with oral and speech dyspraxia, and intellectual disability. Rolandic seizures occur during a period of significant brain maturation. During this time, dysfunction of neural network activities such as focal discharges may be associated with specific developmental disabilities resulting in specific cognitive impairments of language, visuo-spatial abilities or attention.
An autosomal recessive disorder characterized by sparse hair, bilateral juvenile cataracts, and poikiloderma, a genodermatosis presenting with mottled pigmentation, telangiectasia and epidermal atrophy. Additional features are short stature, dystrophic and thin nails, and genital, skeletal and dental abnormalities. RTS1 is not associated with an increased risk of cancer.
An autosomal recessive disorder characterized by dermatological features such as skin atrophy, pigmentation abnormalities, and telangiectasia. It is frequently accompanied by juvenile cataract, saddle nose, congenital bone defects, disturbances of hair growth, hypogonadism, and an increased risk of osteosarcoma in childhood and skin cancer later in life.
Roussy-Levy hereditary areflexic dystasia
Autosomal dominant disorder that resembles Charcot-Marie-Tooth disease type 1 in that it presents with foot deformity, weakness and atrophy of distal limb muscles, especially the peronei, and absent tendon reflexes. The phenotype differs, however, in that it includes static tremor of the upper limbs and gait ataxia.
A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, intellectual disability and a propensity for development of malignancies.
A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, intellectual disability and a propensity for development of malignancies. Some individuals with RSTS2 have less severe mental impairment, more severe microcephaly, and a greater degree of changes in facial bone structure than RSTS1 patients.
A syndrome characterized by genomic instability, progeroid features, and susceptibility toward early onset hepatocellular carcinoma.
Sacral agenesis with vertebral anomalies
A disorder characterized by abnormalities of the spine, including sacral agenesis, abnormal ossification of all vertebral bodies, and a persistent notochordal canal during development.
Form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant.
A craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly.
Early-onset myopathy with fatal cardiomyopathy
Myopathy, early-onset, with fatal cardiomyopathy
An autosomal recessive, early-onset muscular disorder characterized by dilated cardiomyopathy, delayed motor development with generalized muscle weakness predominantly affecting proximal and distal lower limbs. Skeletal muscle biopsies show minicore-like lesions with mitochondrial depletion and sarcomere disorganization, centralized nuclei, and type 1 fiber predominance. Dystrophic changes become apparent in the second decade. Cardiac muscle biopsies show disruption of myocardial architecture, nuclear hypertrophy, and endomysial fibrosis. Sudden death may occurr due to cardiomyopathy.
Sialic acid storage disease (SASD). SASDs are autosomal recessive neurodegenerative disorders characterized by hypotonia, cerebellar ataxia and intellectual disability. They are caused by a defect in the metabolism of sialic acid which results in increased urinary excretion of unconjugated sialic acid, specifically N-acetylneuraminic acid. Enlarged lysosomes are seen on electron microscopic studies. Clinical symptoms of SD present usually at age less than 1 year and progression is slow.
Salt and pepper developmental regression syndrome
Epilepsy syndrome infantile-onset symptomatic
A rare autosomal recessive disorder characterized by infantile onset of severe, recurrent and refractory seizures, failure to thrive, psychomotor delay, developmental stagnation, and cortical blindness. Deafness is observed in some patients. Affected individuals have patches of skin hypo- or hyperpigmentation on the trunk, face, and extremities.
An autosomal recessive syndrome characterized by pre- and postnatal microcephaly, trigonocephaly, congenital bilateral cataract, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, specific brain changes such as loss of periventricular white matter, thin corpus callosum, and delayed myelinization.
An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.
Sarcosine dehydrogenase complex deficiency
A metabolic disorder characterized by an increased concentration of sarcosine in plasma and an increased excretion of sarcosine in urine. Sarcosinemia is most probably a benign condition without significant clinical problems. Some reports have associated sarcosinemia with intellectual disability and neurologic problems.
A rare skeletal dysplasia with characteristic dysmorphic and radiographic findings, as well as early developmental delay, primarily involving speech, with eventual normal cognition. Clinical findings include marked short stature, prominent forehead with an enlarged anterior fontanel, prominent eyes with cataracts, narrow nasal bridge with a convex nasal ridge, micrognathia, clubfoot, brachydactyly, and short distal phalanges of fingers. Radiographic changes include platyspondyly, irregular end plates of vertebral bodies, and hypoplasia of the odontoid process with cervical instability in the spine, coxa valga, overtubulation, metaphyseal flaring and megaepiphyses in the long bones, while the hands and feet exhibit short phalanges, metacarpals and metatarsals, cone-shaped epiphyses of phalanges, and accessory ossification centers of metacarpals and metatarsals.
A disease characterized by aplasia cutis congenita of the scalp, breast anomalies that range from hypothelia or athelia to amastia, and minor anomalies of the external ears. Less frequent clinical characteristics include nail dystrophy, dental anomalies, cutaneous syndactyly of the digits, and renal malformations. Penetrance appears to be high, although there is substantial variable expressivity within families.
Progressive muscular atrophia beginning in the lower legs and affecting the shoulder region earlier and more severely than distal arm.
Scapuloperoneal myopathy, X-linked dominant
A disease characterized by progressive muscle weakness and wasting, upper and lower limbs weakness, foot drop, scapular winging, and myopathic changes on muscle biopsy. Most affected individuals become wheelchair-bound.
Amyotrophy neurogenic scapuloperoneal New England type
A clinically variable neuromuscular disorder characterized by neurogenic scapuloperoneal amyotrophy, laryngeal palsy, congenital absence of muscles, progressive scapuloperoneal atrophy and progressive distal weakness and amyotrophy.
A disease characterized by clinical features of Prader-Willi syndrome, including neonatal hypotonia with poor suck, feeding problems in infancy, obesity, developmental delay, short stature, and hypogonadism. Additionally, patients manifest autism spectrum disorder. Some patients have dysmorphic facial features.
An autosomal recessive pleiotropic disorder characterized by spondyloepiphyseal dysplasia, renal dysfunction and immunodeficiency. Arteriosclerosis may also occur in some case.
Schimmelpenning-Feuerstein-Mims syndrome
A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.
Form of NAGA deficiency characterized by early-onset neuroaxonal dystrophy and neurological signs (convulsion during fever, epilepsy, psychomotor retardation and hypotonia). NAGA deficiency is typically classified in three main phenotypes: NAGA deficiency type I (Schindler disease or Schindler disease type I) with severe manifestations; NAGA deficiency type II (Kanzazi disease or Schindler disease type II) which is mild; NAGA deficiency type III (Schindler disease type III) characterized by mild-to-moderate neurologic manifestations. NAGA deficiency results in the increased urinary excretion of glycopeptides and oligosaccharides containing alpha-N-acetylgalactosaminyl moieties. Inheritance is autosomal recessive.
Schinzel-Giedion midface retraction syndrome
A disorder characterized by severe intellectual disability, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia.
Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid.
Schizophrenia with or without an affective disorder
A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
Schizophrenia 15 with or without an affective disorder
Schizophrenia susceptibility locus chromosome 22q13-related
Schizophrenia susceptibility locus chromosome 2p16-related
Schizophrenia 18 with or without an affective disorder
Schizophrenia 19 with or without an affective disorder
Schizophrenia susceptibility locus chromosome 11q-related
Schizophrenia susceptibility locus chromosome 22-related
Schizophrenia susceptibility locus chromosome 1q-related
Schmid type metaphyseal chondrodysplasia
Dominantly inherited disorder of the osseous skeleton. The cardinal features of the phenotype are mild short stature, coxa vara and a waddling gait. Radiography usually shows sclerosis of the ribs, flaring of the metaphyses, and a wide irregular growth plate, especially of the knees. A variant form of SMCD is spondylometaphyseal dysplasia Japanese type. It is characterized by spinal involvement comprising mild platyspondyly, vertebral body abnormalities, and end-plate irregularity.
Chondrodysplasia, lethal neonatal, with snail-like pelvis
A rare, lethal autosomal recessive skeletal dysplasia characterized by snail-like configuration of the hypoplastic iliac bone, short-limbed dwarfism, short ribs, and flattened, hypoplastic vertebral bodies. SHNKND is lethal in the neonatal period.
Eccrine tumors with ectodermal dysplasia
Keratosis palmoplantaris with cystic eyelids, hypodontia and hypotrichosis
A rare ectodermal dysplasia, characterized chiefly by cysts of the eyelid margins, palmoplantar keratoderma, hypodontia, hypotrichosis and nail dystrophy. Multiple eyelid apocrine hidrocystomas are the hallmark of this condition, although they usually appear in adulthood. The concomitant presence of eccrine syringofibroadenoma in most patients and of other adnexal skin tumors in some affected subjects indicates that Schopf-Schulz-Passarge syndrome is a genodermatosis with skin appendage neoplasms.
Intellectual developmental disorder, autosomal dominant 17
An autosomal dominant intellectual developmental disorder characterized by intellectual disability in combination with distinct craniofacial features and genital abnormalities.
A cancer syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves.
A cancer predisposition syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves.
Rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses.
An autosomal recessive form of liver disease with onset in infancy. Affected infants have jaundice, cholestasis, acholic stools, and progressive liver dysfunction resulting in fibrosis and cirrhosis. Cholangiography shows patent biliary ducts, but there are bile duct irregularities.
An autosomal recessive sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients.
A sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients.
Bleeding abnormality due to deficiency of platelet binding of factor X
Prothrombin consumption inhibitor familial
A mild bleeding disorder due to impaired surface exposure of procoagulant phosphatidylserine (PS) on platelets and other blood cells, following activation with Ca(2+)-elevating agents.
A condition characterized by red blood cells agglutination upon exposure to almost all human sera, but not to autologous serum or the sera of newborns. The condition becomes apparent during blood typing and cross-matching in the laboratory. SDPS depends on the strength of expression of the Sd(a) antigen on red blood cells. Most people have weak anti-Sd(a) antibodies in their serum, which is usually of no clinical importance, but can result in red cell agglutination if they are transfused with cells showing strong Sd(a) expression.
Characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.
Seborrhea-like dermatitis with psoriasiform elements
Characterized by a chronic fine diffuse scaly erythematous rash on the face, particularly on the chin, nasolabial folds and eyebrows, around earlobes and over the scalp. The rash exacerbate in the winter, with emotional stress and after strenuous physical activity. Hyperkeratosis of skin over the elbows, knees, palms, soles and metacarpophalangeal joints is evident. There is no arthralgia, arthritis or neurological disorders.
A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability.
A form of Seckel syndrome, a rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability.
An autosomal recessive metabolic disease characterized by increased urinary erythritol and sedoheptulose. Neonatal cholestasis, hypoglycemia, anemia, congenital arthrogryposis multiplex, multiple contractures and dysmorphisms have been reported in SHPKD patients, but the relationship of these features to the SHPKD is unclear.
Autosomal recessive DOPA-responsive dystonia
Autosomal recessive infantile parkinsonism
Dystonia, DOPA-responsive, autosomal recessive
A form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA.
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS2 inheritance is autosomal dominant.
Benign familial neonatal-infantile epilepsy
Benign familial neonatal-infantile seizures
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant.
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS5 inheritance is autosomal dominant.
Convulsions, benign familial infantile, 6
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant.
Benign neonatal epilepsy 1 and/or myokymia
Benign neonatal epilepsy 1 with myokymia
Benign neonatal epilepsy atypical severe
Convulsions benign familial neonatal 1 with myokymia
A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia.
Benign familial neonatal convulsions type 2
A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset.
Seizures, cortical blindness, and microcephaly syndrome
A severe autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, short stature, and cortical blindness.
Seizures, early-onset, with neurodegeneration and brain calcification
An autosomal recessive neurodegenerative disorder clinically characterized by refractory seizures apparent in the first year of life, mild early developmental delay, and developmental regression after seizure onset. Other features include hypotonia, hyperreflexia, peripheral spasticity, poor eye contact, absent speech, poor head control, and inability to walk. Brain imaging shows reduced white matter volume with delayed myelination, and punctate calcifications.
Seizures, scoliosis, and macrocephaly/microcephaly syndrome
Seizures-scoliosis-macrocephaly syndrome
An autosomal recessive syndrome characterized by seizures, intellectual disability, hypotonia, scoliosis, macrocephaly, hypertelorism and renal dysfunction.
Seizures, sensorineural deafness, ataxia, impaired intellectual development, and electrolyte imbalance
Epilepsy ataxia sensorineural deafness and tubulopathy
A complex disorder characterized by generalized seizures with onset in infancy, delayed psychomotor development, ataxia, sensorineural hearing loss, hypokalemia, metabolic alkalosis, and hypomagnesemia.
Selective pituitary thyroid hormone resistance
Familial hyperthyroidism due to inappropriate thyrotropin secretion
Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established.
Juvenile nephronophthisis with Leber amaurosis
A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.
Sensory ataxic neuropathy dysarthria and ophthalmoparesis
Mitochondrial spinocerebellar ataxia-epilepsy syndrome
Sensory ataxic neuropathy with mitochondrial DNA deletions autosomal recessive
A systemic disorder resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include myopathy, seizures, and hearing loss.
Septo-optic dysplasia with growth hormone deficiency
A clinically heterogeneous disorder defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia with panhypopopituitarism, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum.
Sessile serrated polyposis cancer syndrome
A rare disease characterized by multiple and/or large serrated polyps developing in the colon, and an increased personal and familial risk of colorectal cancer. A patient is diagnosed with SSPCS if at least one of the following criteria is met: the presence of at least five sessile serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter; the presence of any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; the presence of more than 20 serrated polyps of any size distributed throughout the colon. Sessile serrated polyps are also known as sessile serrated adenomas (SSA) and are estimated to be responsible for 20 to 35% of all colon cancers. Individuals with SSPCS may have a strong personal or family history of extracolonic cancers.
Severe combined immunodeficiency Athabaskan type
A variety of SCID with sensitivity to ionizing radiation. A founder mutation has been detected in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency
Severe combined immunodeficiency autosomal recessive T-cell negative/B-cell negative/NK-cell negative due to adenosine deaminase deficiency
Severe combined immunodeficiency autosomal recessive T-cell-negative/B cell-negative/NK cell-negative due to adenosine deaminase deficiency
Severe combined immunodeficiency due to ADA deficiency
An autosomal recessive disorder accounting for about 50% of non-X-linked SCIDs. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive
SCID T cell-negative B cell-negative NK cell-positive
Severe combined immunodeficiency autosomal recessive T cell-negative/B cell-negative/NK cell-positive
Severe combined immunodeficiency autosomal recessive T-cell negative/B-cell negative/NK-cell positive
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation
Severe combined immunodeficiency with sensitivity to ionizing radiation
A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.
Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative
Severe combined immunodeficiency autosomal recessive T cell-negative/B cell-positive/NK cell-negative
Severe combined immunodeficiency autosomal recessive T-cell negative/B-cell positive/NK-cell negative
Severe combined immunodeficiency due to NHEJ1 deficiency
Autosomal recessive T-cell-negative, B cell-negative, NK cell-positive, severe combined immunodeficiency with microcephaly, growth retardation and sensitivity to ionizing radiation
SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. NHEJ1-SCID is characterized by a profound T- and B-lymphocytopenia associated with increased cellular sensitivity to ionizing radiation, microcephaly and growth retardation. Some patients may manifest SCID with sensitivity to ionizing radiation without microcephaly and mild growth retardation, probably due to hypomorphic NHEJ1 mutations.
Severe combined immunodeficiency X-linked T-cell-negative/B-cell-positive/NK-cell-negative
Severe combined immunodeficiency X-linked T cell-negative/B cell-positive/NK cell-negative
Severe combined immunodeficiency X-linked T-cell negative/B-cell positive/NK-cell negative
An autosomal recessive syndrome characterized by severe intellectual disability, hypohidrosis, dental enamel hypoplasia, and hyperkeratosis of the palms and soles. Some may develop mild microcephaly.
An autosomal dominant syndrome characterized by delayed psychomotor development, intellectual disability of variable severity, macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, and hypotonia. Some patients may also have atrial septal defect, episodic hypoglycemia, changes in bone mineral density, and/or seizures.
A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death.
A heart disorder characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. It causes syncope and sudden death. SQT3 has a unique ECG phenotype characterized by asymmetrical T waves.
Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans
Osteochondritis dissecans, short stature, and early-onset osteoarthritis
An autosomal dominant disease characterized by short stature, advanced bone maturation, early-onset osteoarthritis, and mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disk disease and osteochondritis dissecans. Osteochondritis dissecans is defined as a separation of cartilage and subchondral bone from the surrounding tissue.
Short stature and microcephaly with genital anomalies
An autosomal recessive disease characterized by growth failure resulting in severe short stature, severe microcephaly, and delayed and dissociated bone age. Additional features include global psychomotor developmental delay, pubertal delay and genital anomalies.
Short stature with microcephaly and distinctive facies
An autosomal recessive disease characterized by dwarfism, microcephaly, and distinctive facial dysmorphism involving frontal bossing, high forehead, sparse hair and eyebrows, telecanthus, mild proptosis, anteverted nares, and flat nasal bridge.
Short stature with non-specific skeletal abnormalities
A condition characterized by short stature, defined as a height less than 2 SD below normal, and no endocrine abnormalities.
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis
An autosomal recessive disorder characterized by disproportionate short stature, defective tooth enamel formation, and skeletal dysplasia with severe scoliosis in some patients. Variable features include facial dysmorphism, hearing impairment, and mildly impaired intellectual development.
Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities
An autosomal recessive developmental disorder with features of a first and second branchial arch syndrome, and with unique rhizomelic skeletal anomalies. Craniofacial abnormalities can lead to conductive hearing loss, respiratory insufficiency, and feeding difficulties. Skeletal features include bilateral humeral hypoplasia, humeroscapular synostosis, pelvic abnormalities, and proximal defects of the femora. Affected individuals may also have some features of a neurocristopathy or abnormal mesoderm development, such as urogenital anomalies, that are distinct from other branchial arch syndromes.
Short stature, brachydactyly, impaired intellectual developmental, and seizures
Short stature, brachydactyly, intellectual developmental disability, and seizures
An autosomal recessive disease characterized by developmental delay, learning disabilities, mild intellectual disability, delayed speech, and skeletal abnormalities. Skeletal features include short stature, brachydactyly, and short metacarpals and metatarsals.
An autosomal recessive disorder characterized by progressive postnatal growth failure, moderate microcephaly, thin long bones, mildly decreased bone density, and elevated serum levels of total IGF1, IGFBP3 and IGFBP5. Levels of circulating free IGF1 are reduced.
Short stature, developmental delay, and congenital heart defects
An autosomal recessive syndrome characterized by short stature, developmental delay, intellectual disability and congenital heart defects including ventricular septal defect, atrial septal defect and patent foramen ovale. Cataract and uveitis are observed in some patients.
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1
An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract.
Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2
An autosomal recessive disorder characterized by reduced growth, skeletal abnormalities, a distinctive craniofacial appearance, and dental anomalies. Cardiac anomalies have been reported in some patients.
Short stature, hearing loss, retinitis pigmentosa, and distinctive facies
An autosomal recessive disorder characterized by childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability.
A condition defined by a standing height more than 2 standard deviations below the mean (or below the 2.5 percentile) for sex and chronological age, compared with a well-nourished, genetically relevant population, in the absence of specific causative disorders.
Short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies
An autosomal recessive syndrome characterized by short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies.
Short stature, microcephaly, and endocrine dysfunction
A disease characterized by short stature and microcephaly apparent at birth, progressive postnatal growth failure, and endocrine dysfunction. In affected adults endocrine features include hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus. Variable features observed in some patients are progressive ataxia, and lymphopenia or borderline leukopenia.
Short stature, oligodontia, dysmorphic facies, and motor delay
An autosomal recessive disorder with phenotypic variability. The main clinical features include endosteal hyperostosis, short stature, oligodontia, mild facial dysmorphisms, and delayed motor development. Some patients show progeroid features.
Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis
A syndrome characterized by severely short long bones, peculiar facies associated with paucity of hair, and nail anomalies. Growth retardation is evident on prenatal ultrasound as early as the second trimester of pregnancy, and affected individuals reach a final stature consistent with a height age of 6 years to 8 years. Relative macrocephaly is present during early childhood but head circumference is markedly low by adulthood. Psychomotor development is normal. Facial dysmorphism includes a long, triangular face with prominent nose and small ears, and affected individuals have an unusual high-pitched voice. Clinodactyly, brachydactyly, and hypoplastic distal phalanges and fingernails are present in association with postpubertal sparse and short hair. Typical skeletal findings include short and thick long bones with mild irregular metaphyseal changes, short femoral necks, and hypoplastic pelvis and sacrum. All long bones of the hand are short, with major delay of carpal ossification and cone-shaped epiphyses. Vertebral body ossification is also delayed.
Short stature, optic nerve atrophy, and Pelger-Huet anomaly
An autosomal recessive syndrome characterized by severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, abnormal nuclear shape in neutrophil granulocytes (Pelger-Huet anomaly), and optic atrophy with loss of visual acuity and color vision.
Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay
An autosomal dominant disorder characterized by facial dysmorphism, severe micrognathia, microcephaly, rhizomelic short stature, and mild developmental delay.
Partial lipodystrophy with Rieger anomaly and short stature
Short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly and teething delay
A rare, multisystem disease characterized by short stature, anomalies of the anterior chamber of the eye, characteristic facial features such as triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, partial lipodystrophy, hernias, hyperextensibility, and delayed dentition. The clinical phenotype can include insulin resistance, nephrocalcinosis, and hearing deficits. Developmental milestones and cognition are normal.
Short-rib thoracic dysplasia 10 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 11 with or without polydactyly
Short-rib thoracic dysplasia 13 with or without polydactyly
Short-rib thoracic dysplasia 14 with polydactyly
Short-rib thoracic dysplasia 15 with polydactyly
Short-rib thoracic dysplasia 16 with or without polydactyly
Short-rib thoracic dysplasia 17 with or without polydactyly
Short-rib thoracic dysplasia 18 with polydactyly
Short-rib thoracic dysplasia 19 with or without polydactyly
Short-rib thoracic dysplasia 2 with or without polydactyly
Short-rib thoracic dysplasia 20 with polydactyly
Short-rib thoracic dysplasia 21 without polydactyly
Short-rib thoracic dysplasia 3 with or without polydactyly
Polydactyly with neonatal chondrodystrophy type I
Polydactyly with neonatal chondrodystrophy type III
Short-rib thoracic dysplasia 4 with or without polydactyly
Short-rib thoracic dysplasia 5 with or without polydactyly
Short-rib thoracic dysplasia 6 with or without polydactyly
Polydactyly with neonatal chondrodystrophy type II
Short-rib thoracic dysplasia 7 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. SRTD7 hallmarks are acromesomelic hypomineralization, campomelia, polysyndactyly, laterality defects, and cystic kidneys.
Short-rib thoracic dysplasia 7/20 with polydactyly, digenic
A digenic form of short-rib thoracic dysplasia caused by double heterozygosity for a mutation in the WDR35 gene and a mutation in the INTU gene. Short-rib thoracic dysplasia is part of a group of ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome.
Short-rib thoracic dysplasia 8 with or without polydactyly
Short-rib thoracic dysplasia 9 with or without polydactyly
Renal dysplasia retinal pigmentary dystrophy cerebellar ataxia and skeletal dysplasia
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. SRTD9 is characterized by phalangeal cone-shaped epiphyses, chronic renal disease, nearly constant retinal dystrophy, and mild radiographic abnormality of the proximal femur. Occasional features include short stature, cerebellar ataxia, and hepatic fibrosis.
Short/branched-chain acyl-CoA dehydrogenase deficiency
2-methylbutyryl-CoA dehydrogenase deficiency
Autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features.
Shprintzen-Goldberg craniosynostosis syndrome
Craniosynostosis with arachnodactyly and abdominal hernias
Marfanoid disorder with craniosynostosis type I
A very rare syndrome characterized by a marfanoid habitus, craniosynostosis, characteristic dysmorphic facial features, skeletal and cardiovascular abnormalities, intellectual disability, developmental delay and learning disabilities.
An X-linked neurodevelopmental disorder manifesting in affected males with intellectual and learning disability, motor and language delay, autism spectrum disorder, attention deficit and hyperactivity disorder, and dysmorphic features. Some patients may have seizures and/or cerebellar atrophy on brain imaging. Carrier females may have mild disease manifestations.
A form of Shwachman-Diamond syndrome, a disorder characterized by hematopoietic abnormalities, exocrine pancreatic dysfunction, and skeletal dysplasia. Intermittent or chronic neutropenia is the most common hematological manifestation, followed by anemia and thrombocytopenia. Some patients progress to bone marrow failure, myelodysplastic syndrome and malignant transformation, with acute myelogenous leukemia being the most common. Exocrine pancreatic dysfunction is generally the first presenting symptom in infancy. Short stature and metaphyseal dysplasia are the most frequent skeletal manifestations. SDS1 inheritance is autosomal recessive.
A form of Shwachman-Diamond syndrome, a disorder characterized by hematopoietic abnormalities, exocrine pancreatic dysfunction, and skeletal dysplasia. Intermittent or chronic neutropenia is the most common hematological manifestation, followed by anemia and thrombocytopenia. Some patients progress to bone marrow failure, myelodysplastic syndrome and malignant transformation, with acute myelogenous leukemia being the most common. Exocrine pancreatic dysfunction is generally the first presenting symptom in infancy. Short stature and metaphyseal dysplasia are the most frequent skeletal manifestations. SDS2 inheritance is autosomal recessive.
Lysosomal storage disease occurring as two types with various manifestations. Type 1 sialidosis (cherry red spot-myoclonus syndrome or normosomatic type) is late-onset and it is characterized by the formation of cherry red macular spots in childhood, progressive debilitating myoclonus, insiduous visual loss and rarely ataxia. The diagnosis can be confirmed by the screening of the urine for sialyloligosaccharides. Type 2 sialidosis (also known as dysmorphic type) occurs as several variants of increasing severity with earlier age of onset. It is characterized by the presence of abnormal somatic features including coarse facies and dysostosis multiplex, vertebral deformities, intellectual disability, cherry-red spot/myoclonus, sialuria, cytoplasmic vacuolation of peripheral lymphocytes, bone marrow cells and conjunctival epithelial cells.
In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant.
Autosomal recessive sick sinus syndrome 1
Familial sinus node disease autosomal recessive
Sinus node disease, familial, autosomal recessive
The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS1 onset is in utero, infancy, or early childhood.
Atrial fibrillation with bradyarrhythmia
Autosomal dominant sick sinus syndrome 2
Familial sinus bradycardia syndrome autosomal dominant
Sick sinus syndrome 2 with or without cardiac noncompaction and/or ascending aorta dilation
Sinus bradycardia syndrome, familial, autosomal dominant
Sinus node disease, familial, autosomal dominant
The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth.
The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors.
The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS4 is characterized by early and progressive sinus node and atrioventricular conduction dysfunction. Some affected individuals are asymptomatic. SSS4 inheritance is autosomal dominant.
Characterized by abnormally shaped red cells resulting in chronic anemia and periodic episodes of pain, serious infections and damage to vital organs. Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular occlusion thus cutting off the blood supply to nearby tissues.
An autosomal recessive disorder characterized by early-onset progressive sensorineural hearing impairment, global developmental delay, regression of motor skills, dystonia, and low body mass index. Some patients have an ichthosis-like appearance of the skin and signs of sensory neuropathy.
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay
An autosomal recessive disease characterized by severe sideroblastic anemia with onset in the neonatal period or infancy, recurrent periodic fevers without an infectious etiology, B-cell lymphopenia and hypogammaglobulinemia. Affected individuals show delayed psychomotor development with variable neurodegeneration. Additional variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy.
An autosomal dominant syndrome characterized by intellectual disability, variable congenital defects affecting cardiac, skeletal, and urogenital systems. Short stature, macrocephaly, hearing impairment, and facial dysmorphism are present in some patients.
A form of Silver-Russell syndrome, a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. SRS1 is caused by epigenetic changes of DNA hypomethylation at the telomeric imprinting control region (ICR1) on chromosome 11p15, involving the H19 and IGF2 genes.
Growth restriction, severe, with distinctive facies
A form of Silver-Russell syndrome, a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. SRS3 inheritance is autosomal dominant.
A form of Silver-Russell syndrome, a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. SRS4 inheritance is autosomal dominant.
A form of Silver-Russell syndrome, a clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. SRS5 inheritance is autosomal dominant.
A condition characterized by pre- and postnatal overgrowth (gigantism), facial dysmorphism and a variety of inconstant visceral and skeletal malformations. Characteristic dysmorphic features include macrocephaly with coarse, distinctive facies with a large protruding jaw, broad nasal bridge and cleft palate. Cardiac defects are frequent.
A severe variant of Simpson-Golabi-Behmel syndrome, a condition characterized by pre- and postnatal overgrowth (gigantism), facial dysmorphism and a variety of inconstant visceral and skeletal malformations.
An autosomal dominant disorder with variable expression. Core features are marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. Dental anomalies include delayed eruption and immature root formation of anterior permanent teeth, early loss of permanent teeth due to short roots, acute root resorption, high caries, and aggressive alveolar bone loss. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments.
A form of Singleton-Merten syndrome, an autosomal dominant disorder characterized by marked aortic calcification, dental anomalies, osteopenia, acro-osteolysis, and to a lesser extent glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical manifestations include particular facial characteristics and abnormal joint and muscle ligaments. SGMRT2 is an atypical form characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies.
Sinoatrial node dysfunction and deafness
A disease characterized by congenital severe to profound deafness without vestibular dysfunction, associated with episodic syncope due to intermittent pronounced bradycardia.
A form of sitosterolemia, an autosomal recessive metabolic disorder characterized by unregulated intestinal absorption of cholesterol, phytosterols and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.
An autosomal recessive neurocutaneous disorder characterized by a combination of severe intellectual disability, spastic di- or tetraplegia and congenital ichthyosis. Ichthyosis is usually evident at birth with varying degrees of erythema and scaling, neurologic symptoms appear in the first or second year of life. Most patients have an IQ of less than 60. Additional clinical features include glistening white spots on the retina, seizures, short stature and speech defects.
Skeletal defects, genital hypoplasia, and impaired intellectual development
A disorder characterized by intellectual disability, craniofacial dysmorphism, microcephaly and short stature. Additional features include absence of the thumbs, hypoplasia of the radii and ulnae, additional vertebrae and ribs, retarded bone age and genital hypoplasia.
Skeletal dysplasia, mild, with joint laxity and advanced bone age
An autosomal recessive disorder characterized by skeletal dysplasia, short stature, short long bones, advanced bone age, joint laxity, and facial dysmorphism.
Skin creases, congenital symmetric circumferential, 1
Circumferential skin creases, Kunze type
Multiple benign ring-shaped skin creases of limbs
Skin creases, multiple benign ring-shaped, of limbs
An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features.
Skin creases, congenital symmetric circumferential, 2
An autosomal recessive genodermatosis characterized by skin fragility with blistering, focal and diffuse palmoplantar keratoderma, hyperkeratotic plaques on the trunk and limbs, and woolly hair with varying degrees of alopecia.
Intellectual disability with seizures, abnormal gait, and distinctive facial features
An autosomal dominant syndrome characterized by psychomotor developmental delay, intellectual disability with delayed speech, febrile and non-febrile seizures, abnormal gait, and facial dysmorphism. Facial features include a prominent maxilla and upper lip that readily reveal the upper gingiva, widely spaced teeth, and a broad nasal tip.
Affected individuals present a reduction in nerve conduction velocities without any clinical signs of peripheral or central nervous system dysfunction. SNCV inheritance is autosomal dominant.
Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features.
Rutledge lethal multiple congenital anomaly syndrome
An autosomal recessive frequent inborn disorder of sterol metabolism with characteristic congenital malformations and intellectual disability. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and low serum cholesterol levels. SLOS occurs in relatively high frequency: approximately 1 in 20,000 to 30,000 births in populations of northern and central European background. Historically, a clinical distinction often was made between classic ('type I') SLOS and the more severely affected ('type II') patients. There is, in reality, a clinical and biochemical continuum from mild to severe SLOS.
Characterized by intellectual disability associated with development and growth delays. Affected persons have characteristic behavioral abnormalities, including self-injurious behaviors and sleep disturbance, and distinct craniofacial and skeletal anomalies.
A rare autosomal recessive osteochondrodysplasia with skeletal features identical to those of Dyggve-Melchior-Clausen syndrome, but with normal intelligence and no microcephaly. It is characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest.
Livedo reticularis and cerebrovascular accidents
An autosomal recessive, systemic non-inflammatory thrombotic vasculopathy characterized by the association of livedo racemosa, and in some cases livedo reticularis, with cerebrovascular disease. Livedo racemosa is a persistent net-like violaceous-cyanotic, mottled discoloration of the skin affecting the legs, the arms, the buttocks and the trunk; livedo reticularis is limited to the extremities and is visible only in the cold. Cerebrovascular features include recurrent transient ischemic attacks, infarcts, and rarely spinal strokes or intracranial or subarachnoid hemorrhages. Headache and vertigo may precede the onset of livedo racemosa and cerebrovascular manifestations by several years. Rare neurologic symptoms include seizures, chorea, or myelopathies.
Intellectual developmental disorder with macrocephaly, speech delay, and dysmorphic facies
An autosomal dominant neurodevelopmental disorder characterized by intellectual disability with a wide range of severity, developmental delay, and impaired speech and language skills. Speech-related problems include dysarthria, speech apraxia, oromotor problems, and stuttering. Additional clinical features are macrocephaly, characteristic facial features such as prominent forehead and hypertelorism, hypotonia, and joint laxity.
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, hypotonia, intellectual disability, autistic features, impairments in speech and language skills, and dysmorphic features including abnormal, cupped, or prominent ears and ocular anomalies.
Developmental and progressive hereditary eye disorder that affects multiple tissues within the eye. Diagnostic features of SVD include fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment.
Sodium-dependent multivitamin transporter deficiency
Neurodegeneration, infantile-onset, biotin-responsive
An autosomal recessive multisystemic metabolic disorder characterized by early infantile onset, progressive neurodegeneration, global developmental delay, and developmental regression with loss of early motor and cognitive milestones. Additional variable features include seizures, ataxia, spasticity, peripheral neuropathy, immune defects, and osteopenia. Treatment with biotin, pantothenic acid, and lipoate may result in clinical improvement.
Solitary median maxillary central incisor
Rare dental anomaly characterized by the congenital absence of one maxillary central incisor.
Sorbitol dehydrogenase deficiency with peripheral neuropathy
An autosomal recessive disorder characterized by motor axonal neuropathy, slowly progressive distal muscle weakness mainly affecting the lower limbs, difficulty walking, and increased serum sorbitol. Additional variable features are distal sensory impairment, upper limb tremor, scoliosis, and mild hearing loss.
Fundus dystrophy, pseudoinflammatory, of Sorsby
Rare autosomal dominant macular disorder with an age of onset in the fourth decade. It is characterized by loss of central vision from subretinal neovascularization and atrophy of the ocular tissues. Generally, macular disciform degeneration develops in the patients eye within 6 months to 6 years.
An autosomal dominant, childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, intellectual disability, advanced bone age, and abnormal craniofacial morphology including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. Common oral findings include: premature eruption of teeth; high, arched palate; pointed chin and, more rarely, prognathism.
An autosomal dominant form of spastic ataxia, a progressive neurodegenerative disorder characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance.
A neurologic disorder characterized by cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. Cognition is not affected.
A neurologic disorder characterized by cerebellar ataxia, ataxic gait, spasticity, and hyperreflexia. Other variable features include dysarthria, dysmetria, mild cognitive impairment, urinary urgency and dystonic positioning.
A slowly progressive neurodegenerative disease characterized by cerebellar ataxia, spastic paraparesis, dysarthria, and optic atrophy.
A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy.
Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy
An autosomal recessive neurodegenerative disorder characterized by early-onset hypotonia which progresses to a pyramidal syndrome with ataxia, spasticity, hyperreflexia, weakness and loss of ambulation. Brain imaging shows cerebellar atrophy and hypomyelinating leukodystrophy.
An autosomal recessive disorder characterized by onset of spastic ataxia in the first years of life. Clinical features include motor neuropathy, cerebellar atrophy, spastic paraparesis, intellectual disability, slow ocular saccades, axial hypotonia, distal muscle weakness and atrophy, and pyramidal symptoms, including hyperreflexia and extensor plantar responses.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay
A neurodegenerative disease characterized by early-onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse.
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Spastic paraplegia 10, autosomal dominant
Spastic paraplegia 11, autosomal recessive
Autosomal recessive spastic paraplegia with thinning of corpus callosum
Spastic paraplegia autosomal recessive complicated with thin corpus callosum
Spastic paraplegia autosomal recessive with mental impairment and thin corpus callosum
Spastic paraplegia 12, autosomal dominant
Spastic paraplegia 13, autosomal dominant
Spastic paraplegia 15, autosomal recessive
Spastic paraplegia and retinal degeneration
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG15 is a complex form associated with additional neurological symptoms such as cognitive deterioration or intellectual disability, axonal neuropathy, mild cerebellar signs, and, less frequently, a central hearing deficit, decreased visual acuity, or retinal degeneration.
Spastic paraplegia 17, autosomal dominant
Spastic paraplegia with amyotrophy of hands and feet
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG17 is characterized by prominent amyotrophy of the hand muscles, the presence of mild to severe pyramidal tract signs and spastic paraplegia. SPG17 is a motor neuron disease overlapping with distal spinal muscular atrophy type 5.
Spastic paraplegia 18, autosomal recessive
Intellectual disability motor dysfunction and joint contractures
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG18 is a severe form with onset in early childhood. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures.
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG2 is characterized by spastic gait and hyperreflexia. In some patients, complicating features include nystagmus, dysarthria, sensory disturbance, intellectual disability, optic atrophy.
Spastic paraplegia 20, autosomal recessive
Spastic paraparesis childhood-onset with distal muscle wasting
Spastic paraplegia autosomal recessive Troyer type
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG20 is characterized by dysarthria, distal amyotrophy, mild developmental delay and short stature.
Spastic paraplegia 21, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG21 is associated with dementia and other central nervous system abnormalities. Subtle childhood abnormalities may be present, but the main features develop in early adulthood. The disease is slowly progressive, and cerebellar and extrapyramidal signs are also found in patients with advanced disease. Patients have a thin corpus callosum and white-matter abnormalities.
Spastic paraplegia 23, autosomal recessive
Spastic paraparesis, vitiligo, premature graying, characteristic facies
Spastic paraplegia with pigmentary abnormalities
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG23 is an autosomal recessive form characterized by childhood-onset of gait difficulties and pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions.
Spastic paraplegia 26, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG26 is a complicated form characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive.
Spastic paraplegia 28, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG28 patients also have distal sensory impairment.
Spastic paraplegia 3, autosomal dominant
Familial spastic paraplegia autosomal dominant 1
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG30 patients have a pure form of the disorder, limited to spastic paraplegia, whereas others may have a complicated form that includes additional features such as cognitive dysfunction, learning disabilities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy. SPG30 is characterized by onset in the first or second decades of unsteady spastic gait and hyperreflexia of the lower limbs. Inheritance can be autosomal dominant or autosomal recessive.
Spastic paraplegia 31, autosomal dominant
Spastic paraplegia 33, autosomal dominant
Spastic paraplegia 35, autosomal recessive, with or without neurodegeneration
Fatty acid hydroxylase-associated neurodegeneration
Leukodystrophy dysmyelinating and spastic paraparesis with or without dystonia
Spastic paraplegia 35, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur.
Spastic paraplegia 39, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG39 is associated with a motor axonopathy affecting upper and lower limbs and resulting in progressive wasting of distal upper and lower extremity muscles.
Spastic paraplegia 4, autosomal dominant
Familial spastic paraplegia autosomal dominant 2
Spastic paraplegia 42, autosomal dominant
Spastic paraplegia 43, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SP43 is characterized by childhood onset of progressive spasticity affecting the lower and upper limbs.
Spastic paraplegia 44, autosomal recessive
Spastic paraplegia 45, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG45 patients manifest intellectual disability, contractures and learning disability.
Spastic paraplegia 46, autosomal recessive
A neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging.
Spastic paraplegia 47, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG47 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity, and severe intellectual disability with poor or absent speech development.
Spastic paraplegia 48, autosomal recessive
Spastic paraplegia 50, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG50 affected individuals present postnatally with early infantile hypotonia, delayed psychomotor development, strabismus, lack of independent walking and severe intellectual disability. They develop progressive spasticity of all limbs with generalized hypertonia, hyperreflexia, and extensor plantar responses by the end of the first year of life. Speech is absent or limited. Pseudobulbar signs, such as drooling, stereotypic laughter, and exaggerated jaw jerk, are part of the clinical picture.
Spastic paraplegia 51, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG51 is a non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest motor and posture impairments often associated with epilepsy and disturbances of cognition, behavior, sensation, and communication.
Spastic paraplegia 52, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG52 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity, and severe intellectual disability with poor or absent speech development. Some patients may have seizures.
Spastic paraplegia 53, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. SPG53 is characterized by pronounced early onset spastic paraparesis of upper and lower limbs, mild intellectual disability, kyphosis, pectus carinatum and hypertrichosis.
Spastic paraplegia 54, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. SPG54 patients have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions.
Spastic paraplegia 55, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations.
Spastic paraplegia 56, autosomal recessive, with or without pseudoxanthoma elasticum
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. In SPG56, upper limbs are often also affected. Some SPG56 patients may have a subclinical axonal neuropathy; others also have pseudoxanthoma elasticum.
Spastic paraplegia 57, autosomal recessive
A complicated form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations.
Spastic paraplegia 5A, autosomal recessive
Spastic paraplegia 6, autosomal dominant
Familial spastic paraplegia autosomal dominant 3
Spastic paraplegia 61, autosomal recessive
A complicated form of spastic paraplegia with polysensory and motor neuropathy. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Spastic paraplegia 62, autosomal recessive
Spastic paraplegia 63, autosomal recessive
Spastic paraplegia 64, autosomal recessive
Spastic paraplegia 7, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG7 is a complex form. Additional clinical features are cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions.
Autosomal dominant spastic paraplegia 72
Autosomal recessive spastic paraplegia 72
Spastic paraplegia 72, autosomal dominant
Spastic paraplegia 72, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG72 is a pure form of spastic paraplegia with onset of difficulty walking and stiff legs associated with hyperreflexia and extensor plantar responses in early childhood. Some patients may have pes cavus or sphincter disturbances. Cognition, speech, and ocular function are normal. SPG72 inheritance is autosomal dominant or recessive.
Spastic paraplegia 73, autosomal dominant
Spastic paraplegia 74, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG74 is characterized by a combination of spastic paraplegia, optic atrophy, and peripheral neuropathy with childhood-onset and slow progression into late adulthood.
Spastic paraplegia 75, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG75 is characterized by onset in early childhood and is associated with mild to moderate cognitive impairment.
Spastic paraplegia 76, autosomal recessive
Spastic paraplegia 77, autosomal recessive
Spastic paraplegia 78, autosomal recessive
Spastic paraplegia 79A, autosomal dominant, with ataxia
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79A is a slowly progressive form characterized by late-onset spastic ataxia, neuropathy, and often optic atrophy.
Spastic paraplegia 79B, autosomal recessive
Neurodegeneration with optic atrophy, childhood-onset
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79B is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction.
Spastic paraplegia 8, autosomal dominant
Spastic paraplegia 80, autosomal dominant
Spastic paraplegia 81, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG81 is a complicated form characterized by white matter abnormalities, hypomyelination with progressive white matter loss, delayed motor development, progressive spasticity, and impaired intellectual development and speech delay. Additional features may include bifid uvula, microcephaly, seizures, and variable ocular anomalies.
Spastic paraplegia 82, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG82 is a complicated form characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy.
Spastic paraplegia 83, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG83 is characterized by juvenile onset of progressive lower limb spasticity resulting in gait instability.
Spastic paraplegia 84, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG84 is characterized by onset of slowly progressive walking difficulties due to lower limb weakness, stiffness, and spasticity in the first 2 decades of life.
Spastic paraplegia 85, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG85 is an autosomal recessive form characterized by onset of motor symptoms in the first few years of life. Patients may have upper limb involvement and demonstrate axonal polyneuropathy. Additional features include optic atrophy, dysarthria, dysphagia, ataxia, and urinary incontinence. Brain imaging may show cerebellar atrophy.
Spastic paraplegia 86, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG86 is an autosomal recessive form associated with impaired intellectual development, poor or absent speech, and behavioral abnormalities. Brain imaging shows thin corpus callosum and white matter abnormalities. Rare patients may have seizures.
Spastic paraplegia 87, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG87 is characterized by onset of lower limb spasticity in infancy or early childhood, and lack of upper limbs and bulbar regions involvement. Affected individuals have mildly delayed walking, spastic gait, and hyperreflexia. Some patients may also have mild intellectual disability or speech problems.
Spastic paraplegia 88, autosomal dominant
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG88 is characterized by onset of symptoms in the first year of life. Most SPG88 patients have a pure form of the disorder, although rarely patients may manifest additional features, including peripheral neuropathy, speech delay, attention deficit hyperactivity disorder, and non-specific brain imaging abnormalities.
Spastic paraplegia 9A, autosomal dominant
Cataracts with motor neuronopathy, short stature, and skeletal abnormalities
Spastic paraparesis with amyopathy, cataracts, and gastroesophageal reflux
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG9A patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency.
Spastic paraplegia 9B, autosomal recessive
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG9B is a complex form characterized by delayed psychomotor development, intellectual disability, and severe motor impairment. Dysmorphic facial features, tremor, and urinary incontinence are variably observed in SPG9B patients.
Spastic paraplegia and psychomotor retardation with or without seizures
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPPRS is an autosomal recessive neurodevelopmental disorder manifesting in infancy. Affected individuals show hypotonia and psychomotor retardation. Most develop seizures.
Spastic paraplegia, intellectual disability, nystagmus, and obesity
An autosomal dominant syndrome characterized by rapid growth in infancy, obesity, global developmental delay, intellectual disability, spastic paraplegia, ocular defects, and dysmorphic facial features.
Spastic paraplegia, optic atrophy, and neuropathy
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPOAN is characterized by spastic paraplegia with progressive joint contractures and spine deformities, loss of independent ambulation by age 10 years, sub-normal vision secondary to congenital optic atrophy, and neuropathy. Inheritance is autosomal recessive.
Spastic tetraplegia and axial hypotonia, progressive
An autosomal recessive, neurologic disorder characterized by loss of motor abilities in the first year of life, after which severe, progressive spastic tetraparesis develops. Affected individuals have severe axial hypotonia, hyperekplexia, hypertonia, and myokymia, reflecting upper motor neuron involvement. Cognitive development may be affected.
Spastic tetraplegia, thin corpus callosum, and progressive microcephaly
A neurodevelopmental disorder characterized by thin corpus callosum, severe progressive microcephaly, severe intellectual disability, seizures, spasticity, and global developmental delay. Most patients are unable to achieve independent walking or speech.
Spasticity, childhood-onset, with hyperglycinemia
An autosomal recessive disorder characterized by childhood-onset of spasticity, spinal lesions, leukodystrophy, optic atrophy in some patients, non-ketotic hyperglycinemia, and defective enzymatic glycine cleavage. Glycine levels in the cerebrospinal fluid are mildly increased in some but not all patients. The increase is less pronounced than in patients with classic non-ketotic hyperglycinemia.
An immunologic disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. Neutrophils of affected individuals lack lactoferrin and show abnormal nuclear segmentation, bilobed nuclei, low alkaline phosphatase, and increased number of neutrophil mitochondria and ribosomes. SGD1 inheritance can be autosomal dominant or recessive.
A form of specific granule deficiency, an autosomal recessive disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. SGD2 is due to defective neutrophil development. Bone marrow findings include hypercellularity, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. Some patients may have additional findings, including delayed development, mild dysmorphic features, and distal skeletal anomalies.
A disorder characterized by a delay in early speech acquisition. It is usually associated with cerebral white matter abnormalities on brain MRI. Some individuals may show disorders in communication, consistent with autism spectrum disorder, or global developmental delay, although others ultimately show normal cognitive function. Penetrance is incomplete and expressivity is variable.
Autosomal dominant speech and language disorder with orofacial dyspraxia
A disorder characterized by severe orofacial dyspraxia resulting in largely incomprehensible speech. Affected individuals have severe impairment in the selection and sequencing of fine orofacial movements which are necessary for articulation, and deficits in several facets of grammatical skills and language processing, such as the ability to break up words into their constituent phonemes.
An infertility disorder characterized by azoospermia due to spermatogenic arrest during meiosis. Meiotic arrest is characterized by germ cells that enter meiosis and undergo the first chromosomal reduction from 4n to 2n, but that are then unable to proceed further. This results in tubules containing spermatocytes as the latest developmental stage of germ cells. Meiotically arrested spermatocytes accumulate in the tubules and degenerate. Both autosomal recessive and autosomal dominant inheritance have been reported.
Spermatogenic failure with defective sperm annulus
An infertility disorder caused by spermatogenesis defects. It results in decreased sperm motility, concentration, and multiple sperm structural defects. The most prominent feature is a defective sperm annulus, a ring structure that demarcates the midpiece and the principal piece of the sperm tail.
An infertility disorder caused by spermatogenesis defects. It results in decreased sperm motility, concentration, and multiple sperm structural defects. Oligozoospermia is usually observed in SPGF11 patients. In addition to oligozoospermia, teratozoospermia and moderate asthenozoospermia is observed in some cases.
An infertility disorder caused by spermatogenesis defects. It results in decreased sperm motility, concentration, and multiple sperm structural defects. Non-obstructive azoospermia, oligozoospermia and oligo-astheno-teratozoospermia are features observed in SPGF12 patients.
A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. Most spermatozoa are made up of headless tails, while a small proportion has an abnormal head-tail junction. A few spermatozoa are made up of tailless heads.
Male infertility due to oocyte activation failure
An autosomal recessive infertility disorder due to failure of oocyte activation and fertilization by sperm that otherwise exhibits normal morphology.
An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. SPGF18 patients present with primary infertility and multiple morphological abnormalities of sperm flagella that result in impaired sperm mobility. Abnormalities include absent, short, coiled, bent, and irregular flagella. SPGF18 inheritance is autosomal recessive.
An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. SPGF19 patients have spermatozoa with absent, short, coiled, bent, and/or irregular-caliber flagella, which impair sperm motility.
An autosomal recessive disorder characterized by male infertility due to non-obstructive azoospermia. Testicular histopathology reveals no round spermatids or spermatozoa in the seminiferous tubules of SPGF2 patients, consistent with meiotic arrest.
An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. SPGF20 patients have spermatozoa with absent, short, coiled, bent, and/or irregular-caliber flagella, which impair sperm motility.
An infertility disorder caused by spermatogenesis defects and characterized by acephalic spermatozoa in the semen of affected individuals. SPGF21 inheritance is autosomal recessive.
An infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in multiple morphologic abnormalities of the flagella, including absent, short, coiled, bent, and irregular-caliber flagella. Malformations of the sperm head have also been observed. In addition, patients exhibit very low sperm concentrations and total sperm counts per ejaculate.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in severe oligozoospermia or azoospermia.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in acephalic spermatozoa.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in multiple morphologic abnormalities of the sperm flagella, including short, irregular, coiled, or absent flagella.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in oligoasthenospermia or non-obstructive azoospermia.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia or oligozoospermia. When produced, spermatozoa are immotile and have abnormal morphology, primarily defects of the acrosome and head-neck junction.
A disorder characterized by primary infertility, sperm morphologic abnormalities, and moderate to severe asthenozoospermia, condition in which the percentage of progressively motile sperm is abnormally low.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia or cryptozoospermia.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in oligozoospermia with a high proportion of acephalic sperm.
An autosomal dominant infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in multiple abnormalities of sperm flagellum, including short, bent, curled, thick, or absent flagella.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in multiple abnormalities of sperm flagellum, including irregular-caliber, short, coiled, or absent flagella.
An autosomal recessive infertility disorder caused by spermatogenesis defects that result in multiple abnormalities of sperm flagellum and severely impaired spermatozoa motility.
An autosomal dominant infertility disorder due to teratozoospermia, with spermatozoa showing anomalies of the head, acrosome, and nucleus.
An autosomal recessive infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic abnormalities, primarily consisting of short or absent flagella, and neck defects at the head-tail junction.
An autosomal recessive infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic abnormalities including short, absent, coiled, bent, or irregular-caliber flagella.
An autosomal recessive infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic anomalies including short, absent, irregularly shaped and coiled flagella, and abnormalities of the head and midpiece.
Azoospermia due to perturbations of meiosis
An infertility disorder characterized by azoospermia, a condition of having no sperm present in the ejaculate. Testicular histology shows arrest of spermatogenesis at the pachytene stage of primary spermatocytes.
An autosomal recessive infertility disorder characterized by severely reduced or absent sperm motility, due to multiple morphologic anomalies such as absent, short, bent, coiled and irregular-caliber tails. Patient spermatozoa may also show morphologic defects of the sperm head.
An autosomal recessive infertility disorder characterized by oligozoospermia, severe asthenozoospermia and flagellar abnormalities such as short, absent, coiled, and irregular-caliber flagella. Some sperm show tapered heads and acrosomal abnormalities.
An autosomal recessive infertility disorder characterized by almost immotile spermatozoa due to multiple morphologic abnormalities of the flagella, including short, absent, coiled, and bent flagella. Some spermatozoa also show abnormalities of the head, acrosome, midpiece, or endpiece.
An autosomal recessive infertility disorder characterized by asthenospermia due to multiple morphologic abnormalities of sperm flagella, including short, absent, coiled, and bent flagella.
An autosomal recessive infertility disorder caused by spermatogenesis defects and characterized by the presence of acephalic spermatozoa in the semen of affected individuals.
An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in severe teratozoospermia. SPGF45 is characterized by multiple morphologic abnormalities of spermatozoa flagella. Some spermatozoa also show abnormalities of the head.
An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in asthenoteratozoospermia. SPGF46 is characterized by multiple morphologic abnormalities of sperm flagella with disorganization of axonemal and periaxonemal structures. Flagella are absent, short, coiled, angulated, and/or of irregular caliber.
An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in asthenoteratozoospermia. SPGF47 is characterized by reduced sperm concentrations and immotile spermatozoa, with short or absent flagella as well as centriolar abnormalities.
An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in non-obstructive azoospermia.
An autosomal recessive infertility disorder characterized by asthenoteratozoospermia and multiple morphologic abnormalities of the sperm flagella, primarily coiled and short flagella, with markedly reduced or absent motility.
Infertility associated with multi-tailed spermatozoa and excessive DNA
Male infertility with large-headed multiflagellar polyploid spermatozoa
An infertility disorder caused by spermatogenesis defects. Semen from affected men show close to 100% morphologically abnormal multiflagellar spermatozoa with low motility, oversized irregular heads, and abnormal midpiece and acrosome.
An autosomal recessive infertility disorder characterized by azoospermia due to meiotic arrest at the zygotene stage of prophase I.
An autosomal recessive infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic abnormalities, including absent, short, bent, coiled and irregular-caliber flagella. Abnormalities of the sperm head, base, and acrosome have also been observed.
An autosomal recessive infertility disorder characterized by azoospermia due to meiotic arrest at the spermatocyte stage.
An autosomal recessive infertility disorder characterized by impaired oocyte fertilization due to oocyte activation failure, in association with structural anomalies in sperm heads.
An autosomal recessive male infertility disorder characterized by oligoteratoasthenozoospermia.Semen analysis shows markedly reduced sperm counts and severely reduced or absent sperm motility.
An autosomal recessive male infertility disorder characterized by asthenozoospermia.Semen analysis shows severely reduced sperm motility.
An autosomal recessive male infertility disorder characterized by severely reduced sperm motility, due to multiple morphologic abnormalities of the flagella.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia, due to error-prone meiosis and spermatogenic arrest at the late pachytene stage.
An autosomal recessive male infertility disorder characterized by absent or severely reduced sperm motility, due to multiple morphological abnormalities of the sperm flagellum.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia, due to sperm maturation arrest.
An infertility disorder caused by spermatogenesis defects. The most prominent feature is the malformation of the acrosome, which can be totally absent in most severe cases. Additional features are an abnormal nuclear shape and abnormal arrangement of the mitochondria of the spermatozoon.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia, due to sperm maturation arrest before the pachytene stage.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia, due to complete meiotic arrest at the primary spermatocyte stage.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia, due to complete metaphase arrest at the spermatocyte stage.
An autosomal recessive male infertility disorder characterized by severe oligozoospermia and reduced progressive sperm motility.
An autosomal recessive male infertility disorder characterized by oligoasthenoteratozoospermia or non-obstructive azoospermia. Some patients have absent sperm due to meiotic arrest at the diplotene stage. Others show low sperm counts and reduced progressive motility.
An autosomal recessive male infertility disorder characterized by asthenoteratozoospermia. Progressive sperm motility is severely reduced or absent due to multiple morphologic abnormalities of the flagella.
An autosomal recessive male infertility disorder characterized by globozoospermia. Affected individuals have a normal sperm count, but spermatozoa are round-headed and lack the acrosome. In addition to pure globozoospermia, some patients have a mixture of acrosomeless spermatozoa and spermatozoa with small or detached acrosomes, which is defined as acrosomal hypoplasia.
An autosomal recessive male infertility disorder characterized by low sperm concentrations, globozoospermia, and absence of sperm acrosome.
Male infertility non-syndromic autosomal recessive
An infertility disorder characterized by non-motile sperm or sperm motility below the normal threshold, low sperm count, increased abnormally structured spermatozoa, and reduced semen volume.
An autosomal recessive male infertility disorder characterized by azoospermia, sperm immotility or necrozoospermia. Hypospermatogenesis and meiotic arrest have also been observed.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia.
An autosomal recessive male infertility disorder characterized by asthenoteratospermia and multiple morphologic abnormalities of the flagella, including coiled, short, angulated, absent, and irregular-caliber flagella, resulting in absent sperm motility.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia due to meiotic arrest.
An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia due to complete meiotic arrest at the spermatocyte zygotene or pachytene stage. Some men exhibit reduced testicular volume and/or reduced testosterone level.
An autosomal recessive disorder characterized by male infertility due to non-obstructive azoospermia resulting from maturation arrest at the spermatocyte stage.
An autosomal recessive male infertility disorder characterized by oligoasthenoteratozoospermia, and abnormally shaped spermatozoa in the semen of affected individuals. Sperm flagella have multiple morphological abnormalities, including short, absent, and irregular caliber flagella.
An autosomal recessive male infertility disorder characterized by oligozoospermia or azoospermia, and abnormally shaped spermatozoa in the semen of affected individuals. Sperm abnormalities include double and triple tails, with amorphous or fragmented and enlarged heads, as well as pinhead sperm. Testicular tissue shows arrest at the round spermatid stage.
An autosomal recessive, male infertility disorder characterized by a high proportion of sperm head anomalies, primarily tapered and microcephalic heads, and an abnormal acrosome structure.
An autosomal recessive, male infertility disorder characterized by asthenoteratozoospermia with acrosome hypoplasia, disruption of the mitochondrial sheath, and reduced progressive sperm motility. The disorder is due to an abnormal acrosome reaction and impaired membrane potential after capacitation.
An infertility disorder characterized by spermatogenesis failure and severe oligozoospermia.
An autosomal recessive, male infertility disorder characterized by reduced or absent progressive sperm motility due to multiple morphologic abnormalities of the flagella, including short, coiled, absent, and irregular-caliber flagella.
Non-obstructive azoospermia and infertility
Oligozoospermia non-obstructive Y-linked
Spermatogenic failure nonobstructive Y-linked
An infertility disorder caused by spermatogenesis defects and characterized by non-obstructive azoospermia due to complete meiotic maturation arrest. SPGF15 inheritance is autosomal recessive.
An infertility disorder caused by spermatogenesis defects. It is characterized by mixed testicular atrophy and azoospermia with meiotic arrest.
An infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic abnormalities, including absent, short, coiled, and irregular-caliber flagella.
A male infertility disorder characterized by non-obstructive azoospermia or oligoasthenoteratozoospermia. Some patients present spermatogenic maturation arrest with an almost complete absence of early and late primary spermatocytes.
A form of spherocytosis, a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH1 is characterized by severe hemolytic anemia. Inheritance can be autosomal dominant or autosomal recessive. Patients with homozygous mutations have a more severe disorder.
Spherocytosis, type 2, autosomal dominant
An autosomal dominant form of hereditary spherocytosis, a group of hematologic disorders characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Clinical manifestations include chronic hemolytic anemia, jaundice, and splenomegaly, with variable severity.
Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH3 is characterized by severe hemolytic anemia. Inheritance is autosomal recessive.
An autosomal dominant form of spherocytosis, a group of hematologic disorders characterized by the presence of numerous abnormally shaped erythrocytes which are generally spheroidal. Affected individuals have anemia, jaundice, and splenomegaly. Clinical severity is variable. Some individuals are asymptomatic, whereas others have severe hemolytic anemia requiring erythrocyte transfusion.
Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Absence of band 4.2 associated with spur or target erythrocytes has also been reported.
Autosomal dominant form of myofibrillar myopathy (MFM), characterized by slowly progressing proximal muscle weakness and dysarthric nasal speech. There is no evidence of cardiomyopathy. Muscle biopsy shows spheroid bodies within the type I muscle fibers.
Spinal and bulbar muscular atrophy X-linked 1
Bulbospinal neuronopathy X-linked recessive
Kennedy spinal and bulbar muscular atrophy
An X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy.
Proximal hereditary motor neuropathy type I
A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit.
Spinal muscular atrophy infantile chronic form
Spinal muscular atrophy intermediate type
An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood.
Spinal muscular atrophy mild childhood and adolescent form
An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood.
Spinal muscular atrophy proximal adult autosomal recessive
An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk.
Spinal muscular atrophy with congenital bone fractures 1
Spinal muscular atrophy, type I, with congenital bone fractures
An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures.
Spinal muscular atrophy with congenital bone fractures 2
Spinal muscular atrophy with progressive myoclonic epilepsy
Hereditary myoclonus with progressive distal muscular atrophy
An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency.
Arthrogryposis multiplex congenita distal X-linked
Spinal muscular atrophy infantile X-linked
Spinal muscular atrophy X-linked lethal infantile
A lethal infantile form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Clinical features include hypotonia, areflexia, and multiple congenital contractures.
Spinal muscular atrophy, infantile, James type
An autosomal dominant form of spinal muscular atrophy, a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAJI is a severe disease characterized by hypotonia manifesting in the first weeks or months of life, delayed motor development, motor regression, and muscle weakness and atrophy primarily affecting distal muscles. Additional variable features include feeding difficulties, poor overall growth, foot deformities, kyphosis, hyperlordosis, scoliosis, vocal cord dysfunction, and respiratory insufficiency.
An autosomal dominant, slowly progressive, lower motor neuron disease. SMAJ is characterized by adult-onset of muscle cramps and fasciculations affecting the proximal and distal muscles of the upper and lower limbs. The disorder results in weakness and mild muscle atrophy later in life.
Spinal muscular atrophy, lower extremity-predominant 1, autosomal dominant
Autosomal dominant childhood proximal spinal muscular atrophy
Autosomal dominant juvenile proximal spinal muscular atrophy
Autosomal dominant Kugelberg-Welander syndrome
A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMALED1 is characterized by muscle weakness predominantly affecting the proximal lower extremities.
Spinal muscular atrophy, lower extremity-predominant 2A, childhood onset, autosomal dominant
An autosomal dominant form of spinal muscular atrophy characterized by early-childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life.
Spinal muscular atrophy, lower extremity-predominant, 2B, prenatal onset, autosomal dominant
Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant
An autosomal dominant neuromuscular disorder characterized by decreased fetal movements, fractures in utero, severe congenital joint contractures, arthrogryposis multiplex congenita, severe hypotonia, muscle atrophy, and respiratory insufficiency and failure due to muscle weakness. Some patients may have dysmorphic facial features and/or abnormalities on brain imaging. Death in early childhood may occur.
Spinal muscular atrophy, proximal, adult, autosomal dominant
A form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAPAD is characterized by proximal muscle weakness that begins in the lower limbs and then progresses to upper limbs, onset in late adulthood (after third decade) and a benign course. Most of the patients remain ambulatory 10 to 40 years after clinical onset.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA1 is caused by expansion of a CAG repeat in the coding region of ATXN1. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA10 is an autosomal dominant cerebellar ataxia (ADCA).
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar ataxia (ADCA). It is a relatively benign, late-onset, slowly progressive neurologic disorder.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar ataxia (ADCA) characterized by slow progression and variable age at onset, ranging from childhood to late adulthood. Intellectual disability can be present in some patients.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA14 is an autosomal dominant cerebellar ataxia (ADCA).
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar ataxia (ADCA). It is very slow progressing form with a wide range of onset, ranging from childhood to adult. Most patients remain ambulatory.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA19 is a relatively mild, cerebellar ataxic syndrome with cognitive impairment, pyramidal tract involvement, tremor and peripheral neuropathy, and mild atrophy of the cerebellar hemispheres and vermis.
Cerebellar degeneration with slow eye movements
Olivopontocerebellar atrophy Holguin type
Spinocerebellar degeneration with slow eye movements
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA2 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA2 is characterized by hyporeflexia, myoclonus and action tremor and dopamine-responsive parkinsonism. In some patients, SCA2 presents as pure familial parkinsonism without cerebellar signs.
Chromosome 11q12 duplication syndrome 260-KB
Spinocerebellar ataxia with spasmodic cough
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA20 is an autosomal dominant, adult-onset form characterized by dysarthria due to spasmodic dysphonia followed by slowly progressive ataxia.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA21 is characterized by onset in the first decades of life of slowly progressive relatively mild cerebellar ataxia associated with slight extrapyramidal features predominant in older patients and cognitive impairment predominant in younger patients.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA23 is an adult-onset autosomal dominant form characterized by slowly progressive gait and limb ataxia, with variable additional features, including peripheral neuropathy and dysarthria.
An autosomal dominant form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA25 is characterized by the onset of lower limb ataxia and gait difficulties in the first few decades of life, although later onset has been reported. There is incomplete penetrance and variable expressivity, even within families.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord.
Cerebellar ataxia, autosomal dominant, FGF14-related
Nystagmus 4, congenital, autosomal dominant
Vestibulocerebellar disorder with predominant ocular signs
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA27A is an autosomal dominant, slowly progressive form characterized by gait disturbances, ataxia with tremor, dysarthria, orofacial dyskinesia, gaze-evoked nystagmus, and learning disabilities. There is significant variability, and patients show various combinations of neurologic features.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA27B is an autosomal dominant, slowly progressive form characterized by the onset of gait and appendicular ataxia in adulthood.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.
Autosomal dominant congenital nonprogressive cerebellar ataxia
An autosomal dominant, congenital spinocerebellar ataxia characterized by early motor delay, hypotonia and mild cognitive delay. Affected individuals develop a very slowly progressive or non-progressive gait and limb ataxia associated with cerebellar atrophy on brain imaging. Additional variable features include nystagmus, dysarthria, and tremor.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATX3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA31 belongs to the autosomal dominant cerebellar ataxias type III (ADCA III) which are characterized by pure cerebellar ataxia without additional signs.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA34 is an autosomal dominant form characterized by the association of progressive cerebellar ataxia with erythrokeratodermia variabilis.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA35 patients commonly show upper limb involvement and torticollis. There is no cognitive impairment.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA36 is characterized by complicated clinical features, with ataxia as the first symptom, followed by characteristic late-onset involvement of the motor neuron system. Ataxic symptoms, such as gait and truncal instability, ataxic dysarthria, and uncoordinated limbs, start in late forties to fifties. Characteristically, affected individuals exhibit tongue atrophy with fasciculation. Progression of motor neuron involvement is typically limited to the tongue and main proximal skeletal muscles in both upper and lower extremities.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA37 is an autosomal dominant form characterized by adult-onset of slowly progressive gait instability, frequent falls, and dysarthria associated with cerebellar atrophy on brain imaging.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA38 is an autosomal dominant form characterized by adult-onset of slowly progressive gait ataxia accompanied by nystagmus. Brain MRI shows cerebellar atrophy.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA40 is an autosomal dominant, slowly progressive form. Brain MRI shows pontocerebellar atrophy along with a global reduction in brain volume.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA42 is a slowly progressive, autosomal dominant form with variable severity.
Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA42ND is an early-onset, severe form associated with motor and cognitive impairment, cerebellar atrophy as well as variable features such as facial dysmorphisms, digital anomalies, microcephaly and epilepsy. SCA42ND inheritance is autosomal dominant.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA44 is a slowly progressive, autosomal dominant form.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA45 is a slowly progressive, autosomal dominant form with onset in adulthood.
Spinocerebellar ataxia, 46, autosomal dominant, with sensory axonal neuropathy
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA46 is a slowly progressive, autosomal dominant form with onset in adulthood.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA47 is an autosomal dominant disease with a highly variable phenotype and incomplete penetrance. Clinical features include developmental disability, ataxia, and seizures.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA48 is an autosomal dominant neurodegenerative disease characterized by onset in mid-adulthood of progressive cognitive decline and gait ataxia, and vermian and hemispheric cerebellar atrophy.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA49 is an autosomal dominant, slowly progressive form characterized by ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals present with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs. Age of disease onset ranges from the second to seventh decades, even within the same family.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA5 is an autosomal dominant cerebellar ataxia (ADCA). It is a slowly progressive disorder with variable age at onset, ranging between 10 and 50 years.
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA50 is an autosomal dominant form characterized by cerebellar ataxia, oculomotor apraxia and other eye movement abnormalities, and cerebellar atrophy on brain imaging.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA6 is an autosomal dominant cerebellar ataxia (ADCA), mainly caused by expansion of a CAG repeat in the coding region of CACNA1A. There seems to be a correlation between the repeat number and earlier onset of the disorder.
Olivopontocerebellar atrophy with retinal degeneration
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA7 belongs to the autosomal dominant cerebellar ataxias type II (ADCA II) which are characterized by cerebellar ataxia with retinal degeneration and pigmentary macular dystrophy.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA8 is an autosomal dominant cerebellar ataxia (ADCA). It is caused by expansion of a CAG repeat in ATXN8, which is translated into a nearly pure polyglutamine protein which forms 1C2-positive inclusions in Purkinje cells and other neurons.
Progressive myoclonic epilepsy with sensory ataxic neuropathy
An autosomal recessive syndrome characterized by headaches and/or seizures manifesting in childhood or adolescence, cerebellar and sensory ataxia, dysarthria, and myoclonus manifesting in early adulthood. Neuropathological findings include spinocerebellar degeneration associated with cortical neuronal degeneration in advanced cases.
Spinocerebellar ataxia, autosomal recessive 4
Spinocerebellar ataxia with saccadic intrusions
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR4 patients manifest ataxic gait with spasticity and hyperreflexia of the lower limbs resulting in difficulty walking. The age at onset is highly variable, ranging from early childhood to adulthood.
Spinocerebellar ataxia, autosomal recessive, 10
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR10 is characterized by onset in the teenage or young adult years of gait and limb ataxia, dysarthria, and nystagmus associated with marked cerebellar atrophy on brain imaging.
Spinocerebellar ataxia, autosomal recessive, 11
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR11 is associated with psychomotor retardation.
Spinocerebellar ataxia, autosomal recessive, 12
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with intellectual disability. Some patients may also show spasticity.
Spinocerebellar ataxia, autosomal recessive, 13
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR13 is characterized by delayed psychomotor development beginning in infancy. Affected individuals show mild to profound intellectual disability with poor or absent speech as well as gait and stance ataxia and hyperreflexia.
Spinocerebellar ataxia, autosomal recessive, 14
Spectrin-associated autosomal recessive cerebellar ataxia 1
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR14 is characterized by delayed psychomotor development, severe early onset gait ataxia, eye movement abnormalities, cerebellar atrophy on brain imaging, and intellectual disability.
Spinocerebellar ataxia, autosomal recessive, 15
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR15 patients manifest cerebellar ataxia in early childhood and delayed motor development with delayed walking. Additional features include dysarthria, upper limb involvement, abnormal eye movements, and hyporeflexia.
Spinocerebellar ataxia, autosomal recessive, 16
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR16 is characterized by truncal and limb ataxia resulting in gait instability. Additionally, patients may show dysarthria, nystagmus, spasticity of the lower limbs, and mild peripheral sensory neuropathy.
Spinocerebellar ataxia, autosomal recessive, 17
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR17 features include non-progressive congenital cerebellar ataxia, mildly delayed walking with an unsteady gait and frequent falls, dysarthria, dysmetria, hypotonia in the extremities, truncal ataxia, increased reflexes in the lower extremities, and intellectual disability.
Spinocerebellar ataxia, autosomal recessive, 18
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR18 features include progressive cerebellar atrophy, delayed psychomotor development, severely impaired gait, ocular movement abnormalities, and intellectual disability.
Spinocerebellar ataxia, autosomal recessive, 2
Cerebellar hypoplasia, non-progressive Norman type
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Additional features often include loss of fine motor skills, dysarthria, nystagmus, cerebellar signs, and delayed cognitive development with intellectual disability.
Spinocerebellar ataxia, autosomal recessive, 20
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR20 is characterized by cerebellar atrophy, ataxia, coarsened facial features, severely delayed psychomotor development with poor or absent speech, and intellectual disability.
Spinocerebellar ataxia, autosomal recessive, 21
Cholestasis, low GGT, acute liver failure, and neurodegeneration syndrome
Spinocerebellar ataxia, autosomal recessive 21, with hepatopathy
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR21 is characterized by cerebellar atrophy and ataxia with onset in early childhood. Patients also manifest recurrent episodes of liver failure, hepatic fibrosis and a peripheral neuropathy.
Spinocerebellar ataxia, autosomal recessive, 22
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR22 patients manifest variable severity of intellectual disability associated with adult-onset cerebellar ataxia.
Spinocerebellar ataxia, autosomal recessive, 23
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR23 patients manifest epilepsy, intellectual disability, and gait ataxia.
Spinocerebellar ataxia, autosomal recessive, 24
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR24 patients manifest gait instability and speech difficulties with onset in childhood. Clinical features include gait and limb ataxia, dysarthria, nystagmus, cataracts, and cerebellar atrophy on brain imaging.
Spinocerebellar ataxia, autosomal recessive, 25
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR25 patients manifest delayed psychomotor development with delayed walking, truncal ataxia, dysmetria, and nystagmus, Cerebellar hypoplasia is seen on brain imaging.
Spinocerebellar ataxia, autosomal recessive, 26
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR26 is a progressive disease characterized by gait and limb ataxia, loss of independent ambulation, oculomotor apraxia, and peripheral neuropathy with distal muscle weakness and areflexia.
Spinocerebellar ataxia, autosomal recessive, 27
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR27 is a progressive disease characterized by gait difficulties, eye movement abnormalities, dysarthria, and difficulty writing. Some patients may lose independent ambulation. Additional features include spasticity of the lower limbs and cognitive impairment.
Spinocerebellar ataxia, autosomal recessive, 28
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR28 patients manifest mild motor developmental delay, gait ataxia, and dysarthria. Some patients show mildly impaired intellectual development. Disease onset is in early childhood.
Spinocerebellar ataxia, autosomal recessive, 29
Neurodevelopmental disorder with hypotonia and cerebellar ataxia
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR29 is a progressive disease characterized by delayed motor development in early infancy followed by difficulty walking due to an ataxic gait or inability to walk, hypotonia, and variably impaired intellectual development.
Spinocerebellar ataxia, autosomal recessive, 30
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR30 is a progressive disease characterized by childhood-onset global developmental delay with variably impaired intellectual development, motor dysfunction, and cerebellar ataxia. Affected individuals may also have psychiatric abnormalities.
Spinocerebellar ataxia, autosomal recessive, 31
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR30 is characterized by global developmental delay, hypotonia, variably impaired intellectual and language development, ataxic gait, tremor, and dysarthria. Most affected individuals have optic atrophy. Additional features may include retinitis pigmentosa, sensorineural deafness, dysmorphic facial features, and possibly endocrine dysfunction.
Spinocerebellar ataxia, autosomal recessive, 32
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR32 is characterized by the onset of gait ataxia in the second or third decades of life. Other classic features include upper limb ataxia, oculomotor signs, dysphagia, and dysarthria. Some patients may have hyper- or hypokinetic movement abnormalities. Brain imaging shows cerebellar atrophy. Atrophy can extend to the brainstem and medullary olives.
Spinocerebellar ataxia, autosomal recessive, 7
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR7 patients show difficulty walking and writing, dysarthria, limb ataxia, and cerebellar atrophy.
Spinocerebellar ataxia, autosomal recessive, 8
Autosomal recessive cerebellar ataxia type 1
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR8 is an autosomal recessive form.
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence.
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
Spinocerebellar ataxia, autosomal recessive, 1
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN2 is an autosomal recessive form associated with peripheral neuropathy and elevated serum alpha-fetoprotein, immunoglobulins and, less commonly, creatine kinase levels. Some SCAN2 patients manifest oculomotor apraxia.
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN3 is an autosomal recessive disorder characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy and distal sensory impairment due to an axonal peripheral neuropathy. Affected individuals have gait disturbances and sometimes manual dexterity difficulties, as well as cerebellar ataxia associated with cerebellar atrophy on brain imaging.
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAX1 is characterized by hypotonia at birth, delayed motor development, gait ataxia, difficulty standing, dysarthria, and slow eye movements. Brain MRI shows cerebellar ataxia.
A benign melanocytic neoplasm composed of epithelioid or spindle cell melanocytes. Spitz nevi usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms.
Split-foot malformation with mesoaxial polydactyly
An autosomal recessive disorder characterized by a split-foot defect, mesoaxial polydactyly, nail abnormalities of the hands, and sensorineural hearing loss.
Split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive
Congenital deafness and split hands and feet
A disease characterized by the association of split-hand/foot malformation with deafness. Split-hand/foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have intellectual disability, ectodermal and craniofacial findings, and orofacial clefting.
Limb deficiencies, distal, with micrognathia
A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have intellectual disability, ectodermal and craniofacial findings, and orofacial clefting.
Split-hand/foot malformation with long bone deficiency 3
Chromosome 17p13.3, telomeric, duplication syndrome
A disease characterized by the association of split-hand/foot malformation with long bone deficiency involving the tibia and fibula. Split-hand/foot malformation is a limb malformation involving the central rays of the autopod. Phenotypic expression is extremely variable between and within families, and even between limbs of a single patient, ranging from syndactyly and oligodactyly to the most severe monodactyly with only a single phalanx. Limb features include median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals.
Spondylo-megaepiphyseal-metaphyseal dysplasia
A skeletal dysplasia characterized by disproportionate short stature with a short and stiff neck and trunk, relatively long limbs that may show flexion contractures of the distal joints, delayed and impaired ossification of the vertebral bodies, the presence of large epiphyseal ossification centers and wide growth plates in the long tubular bones, and numerous pseudoepiphyses of the short tubular bones in hands and feet.
A chronic rheumatic disease with multifactorial inheritance. It includes a spectrum of related disorders comprising ankylosing spondylitis, a subset of psoriatic arthritis, reactive arthritis (e.g. Reiter syndrome), arthritis associated with inflammatory bowel disease and undifferentiated spondyloarthropathy. These disorders may occur simultaneously or sequentially in the same patient, probably representing various phenotypic expressions of the same disease. Ankylosing spondylitis is the form of rheumatoid arthritis affecting the spine and is considered the prototype of seronegative spondyloarthropathies. It produces pain and stiffness as a result of inflammation of the sacroiliac, intervertebral, and costovertebral joints.
Congenital scoliosis with unilateral unsegmented bar
Disorder characterized by short stature and vertebral, carpal and tarsal fusions.
Spondylocostal dysostosis 1, autosomal recessive
A condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life.
Spondylocostal dysostosis 2, autosomal recessive
Spondylocostal dysostosis 3, autosomal recessive
Spondylocostal dysostosis 4, autosomal recessive
A rare condition of variable severity characterized by vertebral and costal anomalies. The main feature include dwarfism, vertebral fusion, hemivertebrae, posterior rib fusion, reduced rib number, and other rib malformations.
Scoliosis, congenital, with or without rib anomalies
A rare condition of variable severity characterized by vertebral and costal anomalies. The main feature include dwarfism, vertebral fusion, hemivertebrae, posterior rib fusion, reduced rib number, and other rib malformations. SCDO5 inheritance can be autosomal dominant or recessive.
Spondylocostal dysostosis 6, autosomal recessive
A form of spondylocostal dysostosis, a condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life.
Spondyloenchondrodysplasia with immune dysregulation
Combined immunodeficiency with autoimmunity and spondylometaphyseal dysplasia
A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone.
Spondyloepimetaphyseal dysplasia with joint laxity, 1, with or without fractures
Spondyloepimetaphyseal dysplasia with joint laxity Beighton type
A bone disease characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. Additional skeletal features include elbow deformities with radial head dislocation, dislocated hips, clubfeet, and tapered fingers with spatulate distal phalanges. Many affected children have an oval face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Palatal abnormalities and congenital heart disease are also observed.
Spondyloepimetaphyseal dysplasia with joint laxity, 2
Spondyloepimetaphyseal dysplasia with joint laxity Hall type
Spondyloepimetaphyseal dysplasia with joint laxity leptodactylic type
Spondyloepimetaphyseal dysplasia with multiple dislocations Hall type
A bone disease characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly. The most distinctive features for differential diagnosis of SEMDJL2 are the slender metacarpals and phalanges and the progressive degeneration of carpal bones; however, these 2 features are evident only in older children and young adults. The soft consistency of cartilage in the airways leads to laryngotracheomalacia with proneness to respiratory obstruction and inspiratory stridor in infancy and childhood.
Spondyloepimetaphyseal dysplasia with joint laxity, 3
An autosomal recessive bone disease characterized by multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones.
Spondyloepimetaphyseal dysplasia, aggrecan type
A bone disease characterized by severe short stature, macrocephaly, severe midface hypoplasia, short neck, barrel chest and brachydactyly. The radiological findings comprise long bones with generalized irregular epiphyses with widened metaphyses, especially at the knees, platyspondyly, and multiple cervical-vertebral clefts.
Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type
Spondyloepimetaphyseal dysplasia bowed-legs type
Spondyloepimetaphyseal dysplasia matrilin-3 type
Spondylo-epi-metaphyseal dysplasia matrilin 3 type
Spondylometaepiphyseal dysplasia matrilin-3 type
An autosomal recessive bone disease characterized by disproportionate early-onset dwarfism, bowing of the lower limbs, lumbar lordosis and normal hands. Skeletal abnormalities include short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, hypoplastic iliac bones and flat, ovoid vertebral bodies.
Spondyloepimetaphyseal dysplasia, Di Rocco type
A skeletal disorder characterized by short stature, joint pain, genu vara and spondyloepimetaphyseal dysplasia involving the hips, knees, ankles, wrists and hands. Patients also exhibit variable degrees of metaphysis and spine involvement. SEMDDR transmission pattern is consistent with autosomal dominant inheritance.
Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type
An autosomal recessive skeletal disorder characterized by spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability.
Spondyloepimetaphyseal dysplasia, Genevieve type
An autosomal recessive disorder characterized by global developmental delay with infantile onset, intellectual disability, skeletal dysplasia, and short stature. Skeletal findings include flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, premature carpal ossification and small carpal bones.
Spondyloepimetaphyseal dysplasia, Isidor-Toutain type
An autosomal dominant bone disease characterized by early postnatal growth deficiency, severe short stature, genu varum, platyspondyly and severe epiphyseal and metaphyseal changes in the lower limbs.
Spondyloepimetaphyseal dysplasia, Krakow type
An autosomal recessive skeletal disorder characterized by severe spondyloepimetaphyseal dysplasia, rhizomelia, mesomelia with significant anterior bowing of all limbs, severe immunodeficiency, and developmental delay.
Spondyloepimetaphyseal dysplasia, Missouri type
Spondyloepimetaphyseal dysplasia type Missouri
Spondylometaepiphyseal dysplasia type Missouri
A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.
Spondyloepimetaphyseal dysplasia, Shohat type
An autosomal recessive skeletal dysplasia that affects cartilage development. It is characterized by vertebral, epiphyseal, and metaphyseal abnormalities, including scoliosis with vertebral compression fractures, flattened vertebral bodies, and hypomineralization of long bones. Affected individuals may exhibit a small trunk, short neck, small limbs, joint laxity, bowlegs, and/or abdominal distension with hepatosplenomegaly.
Spondyloepimetaphyseal dysplasia, short limb-hand type
SMED short limb-abnormal calcification type
Spondylometaepiphyseal dysplasia short limb-abnormal calcification type
Spondylometaepiphyseal dysplasia short limb-hand type
A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping.
Spondyloepimetaphyseal dysplasia, sponastrime type
Short limb dwarfism with saddle nose, spinal alterations and metaphyseal striation
Spondylar and nasal alterations with striated metaphyses
An autosomal recessive bone disease characterized by spine abnormalities, mid-face hypoplasia with a depressed nasal bridge, and striation of the metaphyses. Additional features include disproportionate short stature with exaggerated lumbar lordosis, scoliosis, coxa vara, limited elbow extension, small dysplastic epiphyses, childhood cataracts, short dental roots, and hypogammaglobulinemia. Disease severity and clinical manifestations are variable. Some patients have intellectual disability.
Spondyloepimetaphyseal dysplasia, Strudwick type
Spondyloepiphyseal dysplasia congenita with dappled metaphyses
Spondylometaepiphyseal dysplasia congenita, Strudwick type
A bone disease characterized by disproportionate short stature from birth, with a very short trunk and shortened limbs, and skeletal abnormalities including lordosis, scoliosis, flattened vertebrae, pectus carinatum, coxa vara, clubfoot, and abnormal epiphyses or metaphyses. A distinctive radiographic feature is irregular sclerotic changes, described as dappled in the metaphyses of the long bones.
Spondyloepimetaphyseal dysplasia, X-linked
An X-linked recessive bone disease characterized by severe short-trunk dwarfism, brachydactyly, metaphyseal flaring of lower extremities, short and broad long bone diaphyses, moderate platyspondyly, normal facies, and normal intelligence.
Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy
An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy.
Spondyloepiphyseal dysplasia congenital type
Disorder characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems.
Spondyloepiphyseal dysplasia Maroteaux type
A clinically variable spondyloepiphyseal dysplasia with manifestations limited to the musculoskeletal system. Clinical features include short stature, brachydactyly, platyspondyly, short and stubby hands and feet, epiphyseal hypoplasia of the large joints, and iliac hypoplasia. Intelligence is normal.
X-linked recessive disorder of endochondral bone formation.
Spondyloepiphyseal dysplasia type Kimberley
Spondyloepiphyseal dysplasias are a heterogeneous group of congenital chondrodysplasias that specifically affect epiphyses and vertebrae. The autosomal dominant SEDK is associated with premature degenerative arthropathy.
Spondyloepiphyseal dysplasia with congenital joint dislocations
A bone dysplasia clinically characterized by dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The disorder is usually evident at birth, with short stature and multiple joint dislocations or subluxations that dominate the neonatal clinical and radiographic picture. During childhood, the dislocations improve, both spontaneously and with surgical treatment, and features of spondyloepiphyseal dysplasia become apparent, leading to arthritis of the hips and spine with intervertebral disk degeneration, rigid kyphoscoliosis, and trunk shortening by late childhood.
Spondyloepiphyseal dysplasia, Kondo-Fu type
SED with elevated blood lysosomal enzymes
A disorder characterized by severely retarded growth, spondyloepiphyseal dysplasia, reduced bone mineral density, and markedly elevated plasma levels of various lysosomal enzymes. Additional features include pectus carinatum, kyphosis, a waddling gait, brachydactyly and dysmorphic facial features. SEDKF transmission pattern is consistent with autosomal recessive inheritance.
Spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and Leber congenital amaurosis
Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis
An autosomal recessive disorder characterized by early-onset retinal degeneration, sensorineural hearing loss, short stature due to spondyloepiphyseal dysplasia, and motor and intellectual delay. Brain imaging shows abnormalities including delayed myelination, leukoencephalopathy, and cerebellar hypoplasia.
Spondyloepiphyseal dysplasia, Stanescu type
An autosomal dominant spondyloepiphyseal dysplasia characterized by glycoproteins accumulation in chondrocytes. Clinical features include progressive joint contractures, premature degenerative joint disease particularly in the knee, hip and finger joints, and osseous distention of the metaphyseal ends of the phalanges causing swolling of interphalangeal joints of the hands. Radiological features include generalized platyspondyly, hypoplastic pelvis, epiphyseal flattening with metaphyseal splaying of the long bones, and enlarged phalangeal epimetaphyses of the hands.
Spondylometaphyseal dysplasia Kozlowski type
A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. It is characterized by postnatal dwarfism, significant scoliosis and mild metaphyseal abnormalities in the pelvis. The vertebrae exhibit platyspondyly and overfaced pedicles.
Spondylometaphyseal dysplasia with cone-rod dystrophy
A disorder characterized by postnatal growth deficiency resulting in profound short stature, rhizomelia with bowing of the lower extremities, platyspondyly with anterior vertebral protrusions, progressive metaphyseal irregularity and cupping with shortened tubular bones, and early-onset progressive visual impairment associated with a pigmentary maculopathy and electroretinographic evidence of cone-rod dysfunction.
Spondylometaphyseal dysplasia with corneal dystrophy
An autosomal recessive disorder characterized by postnatal growth deficiency, profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding, and intellectual disability.
A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDAX is characterized by metaphyseal changes of truncal-juxtatruncal bones, including the proximal femora. Main clinical features are postnatal growth failure, rhizomelic short stature in early childhood evolving into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and function rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on fundoscopic examination and cone-rod dystrophy on electroretinogram. The radiological hallmarks include short ribs with flared, cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora.
Spondylometaphyseal dysplasia, corner fracture type
Spondylometaphyseal dysplasia, Sutcliffe type
Sutcliffe type of spondylometaphyseal dysplasia
An autosomal dominant form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDCF is characterized by flake-like, triangular, or curvilinear ossification centers at the edges of irregular metaphyses that simulate fractures. These corner fractures involve the distal tibia, the ulnar aspect of the distal radius, the proximal humerus, and the proximal femur. They represent irregular ossification at the growth plates and secondary ossification centers.
Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type
Chondrodysplasia, Megarbane-Dagher-Melike type
An autosomal recessive disease characterized by pre- and postnatal short stature, developmental delay, dysmorphic facial appearance, narrow chest, prominent abdomen, platyspondyly, and short limbs.
Spondylometaphyseal dysplasia, Pagnamenta type
A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDP is an autosomal recessive form characterized by short stature and mild platyspondyly with no disproportion between the limbs. Mild metaphyseal changes are present.
Spondylometaphyseal dysplasia, Sedaghatian type
Congenital lethal metaphyseal chondrodysplasia
A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDS is a neonatal lethal form characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, cardiac conduction defects, and central nervous system abnormalities.
A syndrome characterized by cataract, loss of vision due to retinal detachment, facial dysmorphism, facial hypotonia, normal height with disproportional short trunk, osteoporosis, immobile spine with thoracic kyphosis and reduced lumbal lordosis.
SPD patients manifest short stature, midface hypoplasia, sensorineural hearing loss, spondyloepiphyseal dysplasia, platyspondyly and brachydactyly.
Spongiform encephalopathy with neuropsychiatric features
Autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms.
Neurodevelopmental disorder with low cholesterol and abnormal urine organic acids
An autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, facial dysmorphisms, low total and LDL-cholesterol, and abnormal urine organic acids.
Squamous cell carcinoma of the head and neck
A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes.
A neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild dysmorphism, ophthalmologic anomalies, feeding difficulties, deafness, and variable congenital malformations of the cardiac and/or urogenital systems.
Stapes ankylosis with broad thumb and toes
Ankylosis of stapes, hyperopia, broad thumbs, broad first toes, and syndactyly
Stapes ankylosis syndrome without symphalangism
An autosomal dominant disorder characterized by hyperopia, a hemicylindrical nose, broad thumbs, great toes, and other minor skeletal anomalies but lacked carpal and tarsal fusion and symphalangism.
A common hereditary macular degeneration. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina.
Macular dystrophy autosomal dominant chromosome 6-linked
Disease characterized by round or oval cystic tumors widely distributed on the back, anterior trunk, arms, scrotum, and thighs.
Dislocated hips and radial heads, carpal coalition, scoliosis, and short stature
A syndrome characterized by dislocated hips and radial heads, fusion of carpal bones, short stature, scoliosis, and cervical spine anomalies. Facial features include prominent forehead, long oval-shaped face, hypertelorism and broad nasal bridge.
A rare blistering mucocutaneous disease that share clinical and histopathologic features with toxic epidermal necrolysis. Both disorders are characterized by high fever, malaise, and a rapidly developing blistering exanthema of macules and target-like lesions accompanied by mucosal involvement. Stevens-Johnson syndrome is a milder disease characterized by destruction and detachment of the skin epithelium and mucous membranes involving less than 10% of the body surface area. Ocular symptoms include ulcerative conjunctivitis, keratitis, iritis, uveitis and sometimes blindness. It can be caused by a severe adverse reaction to particular types of medication, although Mycoplasma infections may induce some cases.
Arthro-ophthalmopathy hereditary progressive
Stickler syndrome membranous vitreous type
An autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
Stickler syndrome 1 non-syndromic ocular
An autosomal dominant form of Stickler syndrome characterized by the ocular signs typically seen in Stickler syndrome type 1 such as cataract, myopia, retinal detachment. Systemic features of premature osteoarthritis, cleft palate, hearing impairment, and craniofacial abnormalities are either absent or very mild.
An autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
An autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. STL5 is characterized by high myopia, vitreoretinal degeneration, retinal detachment, mild to moderate sensorineural hearing loss, short stature in childhood, and absence of cleft palate and Pierre Robin sequence.
A form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondyly and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. STL6 is an autosomal recessive form characterized by early-onset progressive hearing loss and progressive myopia, with variable manifestation of facial dysmorphism and skeletal anomalies.
A syndrome characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness.
STING-associated vasculopathy, infantile-onset
An autoinflammatory disease characterized by early-onset systemic inflammation and cutaneous vasculopathy, resulting in severe skin lesions. Violaceous, scaling lesions of fingers, toes, nose, cheeks and ears progress to acral necrosis in most of the patients. Some patients have severe interstitial lung disease.
Stomatin-deficient cryohydrocytosis with neurologic defects
GLUT1 deficiency syndrome with pseudohyperkalemia and hemolysis
A rare form of stomatocytosis characterized by episodic hemolytic anemia, cold-induced red cells cation leak, erratic hyperkalemia, neonatal hyperbilirubinemia, hepatosplenomegaly, cataracts, seizures, intellectual disability, and movement disorder.
A rare autosomal dominant disease characterized by mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis.
Striatal degeneration, autosomal dominant 1
A movement disorder affecting the striatal part of the basal ganglia and characterized by bradykinesia, dysarthria and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present.
Striatal degeneration, autosomal dominant 2
An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis.
Striatonigral degeneration, childhood-onset
An autosomal recessive neurological disorder characterized by sudden childhood onset of developmental regression. Affected children develop impaired movements with dystonia, progressively become non-ambulatory and non-verbal, and exhibit striatal abnormalities on MRI.
Apple peel syndrome with microcephaly and ocular anomalies
Jejunal atresia with microcephaly and ocular anomalies
An autosomal recessive congenital disorder characterized by intestinal atresia, ocular anomalies, microcephaly, and renal and cardiac abnormalities in some patients. The disease has features of a ciliopathy, and lethality in early childhood is observed in severe cases.
Structural brain anomalies with impaired intellectual development and craniosynostosis
A disease characterized by microcephaly, agenesis of corpus callosum, abnormal conformation of the ventricles and posterior fossa, hypoplasia of both cerebellar hemispheres, colpocephaly, and partial absence of the cerebellar vermis with fusion of the cerebellar hemispheres. Intellectual development is moderately to severely impaired. Bicoronal synostosis, scoliosis, and tethered cord may be present.
Structural heart defects and renal anomalies syndrome
An autosomal recessive syndrome characterized by central nervous system, cardiac, renal, and digit abnormalities. Clinical features include ventricular and atrial septal defects, truncus arteriosus, tetralogy of Fallot, partial anomalous pulmonary venous return, renal cysts, renal failure, and generalized edema. Some patients show partial agenesis of corpus callosum.
A syndrome characterized by an intracranial vascular anomaly, leptomeningeal angiomatosis, most often involving the occipital and posterior parietal lobes. The most common features are facial cutaneous vascular malformations (port-wine stains), seizures, and glaucoma. Stasis results in ischemia underlying the leptomeningeal angiomatosis, leading to calcification and laminar cortical necrosis. The clinical course is highly variable and some children experience intractable seizures, intellectual disability, and recurrent stroke-like episodes.
A familial form of stuttering, a disturbance in the normal fluency and time patterning of speech, characterized by frequent repetitions or prolongations of sounds or syllables, and by interruptions of speech known as blocks. STUT1 inheritance is autosomal dominant.
Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome
A form of Stuve-Wiedemann syndrome, an autosomal recessive disease characterized by bowing of tubular bones and other skeletal and craniofacial abnormalities, respiratory distress, feeding difficulties, and hyperthermic episodes. Most patients do not survive past infancy.
A form of Stuve-Wiedemann syndrome, an autosomal recessive disease characterized by bowing of tubular bones and other skeletal and craniofacial abnormalities, respiratory distress, feeding difficulties, and hyperthermic episodes. Most patients do not survive past infancy. STWS2 patients manifest skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response.
SBH is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.
SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.
Succinic semialdehyde dehydrogenase deficiency
Succinate semialdehyde dehydrogenase deficiency
A rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, intellectual disability, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances.
Succinyl-CoA:3-oxoacid CoA transferase deficiency
Succinyl-CoA:3-ketoacid CoA-transferase deficiency
Succinyl-CoA:3-ketoacid-CoA transferase deficiency
Succinyl-CoA:acetoacetate transferase deficiency
Succinyl-CoA-3-ketoacid-CoA transferase deficiency
A disorder of ketone body metabolism, characterized by episodic ketoacidosis. Patients are usually asymptomatic between episodes.
Unexpected rapid death due to cardiovascular collapse in a short time period, generally within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as chest pain and cardiac arrhythmias, particularly ventricular tachycardia, can lead to the loss of consciousness and cardiac arrest followed by biological death.
An autosomal recessive disease characterized by sudden death due to unexpected cardiac arrest following ingestion of small amounts of alcohol.
A disease characterized by sudden death within the first 2 years of life due to unexpected cardiac arrest. Some patients manifest hypertrophic cardiomyopathy, lipid accumulation in myocardium, degeneration of mitochondrial cristae, metabolic acidosis, and elevated plasma lactate levels. SCFI transmission pattern is consistent with autosomal recessive inheritance.
SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive.
Sudden infant death with dysgenesis of the testes syndrome
Autosomal recessive disorder. Affected infants appear normal at birth, develop signs of visceroautonomic dysfunction early in life, and die before 12 months of age of abrupt cardiorespiratory arrest. Features included bradycardia, hypothermia, severe gastroesophageal reflux, laryngospasm, bronchospasm, and abnormal cardiorespiratory patterns during sleep. Genotypic males with SIDDT had fetal testicular dysgenesis and ambiguous genitalia, with findings such as intraabdominal testes, dysplastic testes, deficient fetal testosterone production, fusion and rugation of the gonadal sac, and partial development of the penile shaft. Female sexual development was normal. Affected infants had an unusual staccato cry, similar to the cry of a goat.
An autosomal recessive syndrome characterized by global developmental delay with poor expressive language, poor fine motor skills and hypotonia, microcephaly, feeding difficulties with failure to thrive, recurrent respiratory infections, cardiovascular malformations, cryptorchidism, happy demeanor, and facial dysmorphism. Distinctive facial features are excessive forehead hair, arched and thick eyebrows with synophrys, epicanthus, hypertelorism, thick eyelids with periorbital fullness, broad nasal bridge, long and smooth philtrum, thin upper lip, and low set prominent ears.
Sulfide:quinone oxidoreductase deficiency
An autosomal recessive disorder of hydrogen sulfide metabolism characterized by a variable phenotype. Some patients present with encephalopathy, clinical manifestations of Leigh syndrome, and may have a fatal disease course. Others are asymptomatic. Additional features may include lactic acidosis and decreased mitochondrial respiratory chain complex IV activity in tissues.
A life-threatening, autosomal recessive neurometabolic disorder characterized by severe neurological impairment. Classic ISOD manifests in the first few hours to days of life and is characterized by intractable seizures, feeding difficulties, rapidly progressive encephalopathy, microcephaly, and profound intellectual disability. Children usually die during the first few months of life. Mild ISOD manifests in infancy or early childhood and is characterized by ectopia lentis that is variably present, developmental delay and regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and rarely acute hemiplegia due to metabolic stroke.
Congenital narrowing of the ascending aorta which can occur sporadically, as an autosomal dominant condition, or as one component of Williams-Beuren syndrome.
Helicoidal peripapillary chorioretinal degeneration
Characterized by symmetrical lesions radiating from the optic disk involving the retina and the choroid.
An autosomal dominant syndrome characterized by facial dysostosis, including hypertelorism, deficiencies of the eyelids and facial bones, cleft palate/velopharyngeal insufficiency, and low-set cupped ears.
Hereditary absence of the proximal interphalangeal joints
A disease characterized by the hereditary absence of the proximal interphalangeal joints. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conductive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.
Symptomatic deficiency in lactate transport
Deficiency of lactate transporter may result in an acidic intracellular environment created by muscle activity with consequent degeneration of muscle and release of myoglobin and creatine kinase. This defect might compromise extreme performance in otherwise healthy individuals.
A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. In SDTY3, there is usually complete and bilateral syndactyly between the fourth and fifth fingers. Usually it is soft tissue syndactyly but occasionally the distal phalanges are fused. The fifth finger is short with absent or rudimentary middle phalanx. The feet are not affected.
A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. SDTY4 is characterized by complete bilateral syndactyly (involving all digits 1 to 5). A frequent association with polydactyly (with six metacarpals and six digits) has been reported. Feet are affected occasionally.
Syndactyly with metacarpal and metatarsal fusion
A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. The characteristic finding in SDTY5 is the presence of an associated metacarpal and metatarsal fusion. The metacarpals and metatarsals most commonly fused are the 4th and 5th or the 3rd and 4th. Soft tissue syndactyly usually affects the 3rd and 4th fingers and the 2nd and 3rd toes.
Syndactyly, mesoaxial synostotic, with phalangeal reduction
Mesoaxial synostotic syndactyly, Malik-Percin type
An autosomal recessive, non-syndromic digit anomaly characterized by mesoaxial osseous synostosis at a metacarpal level, reduction of one or more phalanges, hypoplasia of distal phalanges of preaxial and postaxial digits, clinodactyly of fifth fingers, and preaxial fusion of toes.
Limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
A rare autosomal recessive form of systemic lupus erythematosus with childhood onset, characterized by high frequency of anti-neutrophil cytoplasmic antibodies and lupus nephritis. Systemic lupus erythematosus is a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
A form of systemic lupus erythematosus, a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. SLEB17 is an X-linked dominant form characterized by onset of systemic autoinflammatory symptoms in the first decades of life.
Autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. Present early in life with hypoketotic hypoglycemia and acute metabolic decompensation, or later in life with skeletal myopathy or cardiomyopathy.
T-cell immunodeficiency with thymic aplasia
An autosomal recessive disorder characterized by selective hypo- or aplasia of the thymus, T-cell immunodeficiency due to impaired T-cell development, and increased susceptibility to viral infections.
T-cell immunodeficiency, congenital alopecia, and nail dystrophy
Severe T-cell immunodeficiency-congenital alopecia-nail dystrophy
A disorder characterized by the association of congenital alopecia, severe T-cell immunodeficiency, and ridging and pitting of all nails.
T-cell immunodeficiency, recurrent infections, and autoimmunity with or without cardiac malformations
A primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect.
T-cell lymphoma, subcutaneous panniculitis-like
An uncommon form of T-cell non-Hodgkin lymphoma, in which cytotoxic CD8+ T-cells infiltrate subcutaneous adipose tissue, and rimming adipocytes in a lace-like pattern. Affected individuals typically present with multiple subcutaneous nodules, systemic B-cell symptoms, and, in a subset of cases, autoimmune disorders, most commonly systemic lupus erythematosus. A subset of patients develop hemophagocytic lymphohistiocytosis. SPTCL transmission pattern is consistent with autosomal recessive inheritance with incomplete penetrance.
T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant
An autosomal dominant disorder characterized by decreased numbers of T cells, particularly cytotoxic CD8+ T cells, and increased susceptibility to recurrent infections, mainly respiratory viral infections. Additional features may include impaired thymic development, skin abnormalities, such as atopic dermatitis, and nail dystrophy.
An autosomal dominant syndrome characterized by macrothrombocytopenia, lymphedema, intellectual disability, developmental delay, and distinctive facial features.
High density lipoprotein deficiency, Tangier Type
An autosomal recessive disorder characterized by near absence of plasma high density lipoproteins, low serum HDL cholesterol, and massive tissue deposition of cholesterol esters. Clinical features include large yellow-orange tonsils, hepatomegaly, splenomegaly, enlarged lymph nodes, and often sensory polyneuropathy.
Autosomal dominant, late-onset distal myopathy. Muscle weakness and atrophy are usually confined to the anterior compartment of the lower leg, in particular the tibialis anterior muscle. Clinical symptoms usually occur at age 35-45 years or much later.
Pierre Robin syndrome with congenital heart malformation and clubfoot
Talipes equinovarus atrial septal defect robin sequence and persistence of left superior vena cava
A disorder characterized by the Robin sequence (micrognathia, glossoptosis and cleft palate), talipes equinovarus and cardiac defects.
Autosomal dominant disorder characterized by fusion of the carpals, tarsals and phalanges, short first metacarpals causing brachydactyly, and humeroradial fusion. TCC is allelic to SYM1, and different mutations in NOG can result in either TCC or SYM1 in different families.
An overgrowth syndrome characterized by a distinctive facial appearance, tall stature and intellectual disability. Facial gestalt is characterized by a round face, heavy horizontal eyebrows and narrow palpebral fissures. Less common features include atrial septal defects, seizures, umbilical hernia, and scoliosis.
Chromosome 22q11.2 deletion syndrome, Opitz phenotype
Opitz oculogenitolaryngeal syndrome, type II
A form of Teebi hypertelorism syndrome, a syndrome characterized by an abnormally increased distance between ocular orbits, and facial features that can resemble craniofrontonasal dysplasia such as prominent forehead, widow's peak, heavy and broad eyebrows, long palpebral fissures, ptosis, high and broad nasal bridge, short nose, low-set ears, natal teeth, thin upper lip and a grooved chin. Some affected individuals have limb, urogenital, umbilical and cardiac defects. Developmental delay and/or impaired intellectual development have been observed in some patients. TBHS1 inheritance is autosomal dominant.
A form of Teebi hypertelorism syndrome, a syndrome characterized by an abnormally increased distance between ocular orbits, and facial features that can resemble craniofrontonasal dysplasia such as prominent forehead, widow's peak, heavy and broad eyebrows, long palpebral fissures, ptosis, high and broad nasal bridge, short nose, low-set ears, natal teeth, thin upper lip and a grooved chin. Some affected individuals have limb, urogenital, umbilical and cardiac defects. Developmental delay and/or impaired intellectual development have been observed in some patients. TBHS2 inheritance is autosomal dominant.
Telangiectasia, hereditary hemorrhagic, 1
Hereditary hemorrhagic telangiectasia of Rendu, Osler, and Weber
A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain.
Telangiectasia, hereditary hemorrhagic, 2
Telangiectasia, hereditary hemorrhagic, 5
A developmental disorder characterized by intellectual disability, epilepsy, hypoplasia or aplasia of the thumb and great toe nails, and broadening and/or elongation of the thumbs and halluces, which have a tubular aspect. Some patients show facial dysmorphism.
Preaxial brachydactyly syndrome Temtamy type
A syndrome characterized by multiple congenital anomalies, intellectual disability, sensorineural deafness, talon cusps of upper central incisors, growth retardation, and bilateral symmetric digital anomalies mainly in the form of preaxial brachydactyly and hyperphalangism.
An autosomal recessive syndrome characterized by intellectual disability, variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus.
Overgrowth, macrocephaly, and intellectual disability syndrome
A disease characterized by overgrowth, macrocephaly, and intellectual disability. Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome.
Digital osseous dysplasia with facial pigmentary defects and multiple frenula
Osseous dysplasia and pigmentary defects
Terminal osseous dysplasia and pigmentary defects
A rare X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin and recurrent digital fibroma during infancy. A significant phenotypic variability is observed in affected females.
Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 1
An autosomal dominant disorder with onset in infancy, characterized by poor overall growth, microcephaly, hypotonia, profound global developmental delay, impaired intellectual development, poor or absent speech, and characteristic dysmorphic facial features, including hypertelorism and abnormal nose. Other variable neurologic and systemic features may also occur.
Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 2
An autosomal dominant disorder characterized by poor overall growth, microcephaly, hypotonia, profound global developmental delay, impaired intellectual development, absent speech, and characteristic dysmorphic facial features, including hypertelorism, abnormal nose, and wide mouth.
Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 3
An autosomal dominant disorder characterized by global developmental delay with poor overall growth, impaired intellectual development, and speech difficulties. More variable features include hypotonia, microcephaly, and dysmorphic facies.
Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 4
An autosomal dominant disorder characterized by global developmental delay with poor overall growth, variably impaired intellectual development, learning difficulties, distal skeletal anomalies, and dysmorphic facies. Some patients have visual or hearing deficits.
Testicular anomalies with or without congenital heart disease
A 46,XY disorder of sex development with variable clinical presentation and defects in testicular differentiation and function. Clinical features include ambiguous genitalia, fused labioscrotal folds, hypospadias, microphallus, and bilateral inguinal hernia containing gonads.
A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
Tetraamelia syndrome, autosomal recessive
A form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS1 patients manifest complete limb agenesis without defects of scapulae or clavicles. Other features include bilateral cleft lip/palate, diaphragmatic defect with bilobar right lung, renal and adrenal agenesis, pelvic hypoplasia, and urogenital defects. TETAMS1 transmission pattern is consistent with autosomal recessive inheritance.
A form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS2 patients manifest limb deformities, bilateral agenesis of the lungs, abnormalities of the pulmonary vasculature, labioscrotal fold aplasia, and dysmorphic features including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, and microretrognathia. TETAMS2 transmission pattern is consistent with autosomal recessive inheritance.
A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis.
Lethal short-limbed platyspondylic dwarfism San Diego type
Platyspondylic lethal skeletal dysplasia San Diego type
A neonatal lethal skeletal dysplasia. Affected individuals manifest severe shortening of the limbs with macrocephaly, narrow thorax, short ribs, and curved femurs.
Cloverleaf skull with thanatophoric dwarfism
Thanatophoric dysplasia with kleeblattschaedel
Thanatophoric dysplasia with straight femurs and cloverleaf skull
A neonatal lethal skeletal dysplasia causing severe shortening of the limbs, narrow thorax and short ribs. Patients with thanatophoric dysplasia type 2 have straight femurs and cloverleaf skull.
A rare autosomal recessive syndrome characterized by generalized overgrowth, developmental delay, learning disabilities, and variable congenital abnormalities including congenital heart defects, renal dysplasia, and skeletal defects.
Thiamine metabolism dysfunction syndrome 2, biotin- or thiamine-responsive type
An autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia.
Thiamine metabolism dysfunction syndrome 4, bilateral striatal degeneration and progressive polyneuropathy type
Bilateral striatal degeneration and progressive polyneuropathy
Striatal necrosis, bilateral and progressive polyneuropathy
A disease characterized by recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy.
Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type
Episodic encephalopathy due to thiamine pyrophosphokinase deficiency
An autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits.
Thiamine-responsive megaloblastic anemia syndrome
Megaloblastic anemia thiamine-responsive with diabetes mellitus and sensorineural deafness
Thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type)
An autosomal recessive disease characterized by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke.
A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC3 is an autosomal recessive form characterized by onset in infancy.
Thrombocytopenia 5 with increased susceptibility to malignancy
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC5 is an autosomal dominant disorder, associated with an increased susceptibility to the development of hematologic and solid malignancies.
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC6 is an autosomal dominant form. Affected individuals may also have bone abnormalities and an increased risk for myelofibrosis.
A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC7 is an autosomal dominant form with highly variable severity, ranging from absence of bleeding symptoms to epistaxis or more severe bleeding episodes.
Thrombocytopenia with beta-thalassemia, X-linked
Thrombocytopenia platelet dysfunction hemolysis and imbalanced globin synthesis
An unusual form of thrombocytopenia associated with beta-thalassemia. Patients have splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and unbalanced (hemo)globin chain synthesis resembling that of beta-thalassemia minor.
Thrombocytopenia, anemia, and myelofibrosis
An autosomal recessive disorder characterized by thrombocytopenia, increased number of giant platelets, and anemia manifesting in early childhood. Bone marrow biopsy shows increased number of megakaryocytes and reticular fibrosis consistent with myelofibrosis.
Radial aplasia-thrombocytopenia syndrome
An autosomal recessive disorder characterized by bilateral absence of the radii with the presence of both thumbs, thrombocytopenia, low numbers of megakaryocytes, and bleeding episodes in the first year of life. Thrombocytopenic episodes decrease with age. Skeletal anomalies range from absence of radii to virtual absence of upper limbs, with or without lower limb defects such as malformations of the hip and knee.
Thrombophilia 13, X-linked, due to factor VIII defect
An X-linked dominant, hemostatic disorder associated with markedly elevated F8 levels, and characterized by severe thrombophilia.
Thrombophilia due to activated protein C resistance
Thrombophilia due to deficiency of activated protein C cofactor
A hemostatic disorder due to defective degradation of factor V by activated protein C. It is characterized by a poor anticoagulant response to activated protein C resulting in tendency to thrombosis.
Thrombophilia due to heparin cofactor 2 deficiency
A hemostatic disorder characterized by a tendency to recurrent thrombosis.
Thrombophilia due to histidine-rich glycoprotein deficiency
A hemostatic disorder characterized by a tendency to thrombosis.
Thrombophilia due to protein C deficiency, autosomal dominant
A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.
Thrombophilia due to protein C deficiency, autosomal recessive
Protein C deficiency autosomal recessive
A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.
Thrombophilia due to protein S deficiency, autosomal dominant
Thrombophilia autosomal dominant due to protein S deficiency
Thrombophilia autosomal recessive due to protein S deficiency
A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Based on the plasma levels of total and free PROS1 as well as the serine protease-activated protein C cofactor activity, three types of THPH5 have been described: type I, characterized by reduced total and free PROS1 levels together with reduced anticoagulant activity; type III, in which only free PROS1 antigen and PROS1 activity levels are reduced; and the rare type II which is characterized by normal concentrations of both total and free PROS1 antigen, but low cofactor activity.
Thrombophilia due to protein S deficiency, autosomal recessive
A very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage.
A multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation.
Thrombophilia due to thrombomodulin defect
Thrombophilia, X-linked, due to factor IX defect
Thrombotic thrombocytopenic purpura, hereditary
Microangiopathic hemolytic anemia congenital
Thrombotic thrombocytopenic purpura familial
An autosomal recessive hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever.
Familial nonmedullary thyroid cancer, papillary
Nonmedullary thyroid carcinoma, papillary
A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
Congenital hypothyroidism due to dyshormonogenesis type 1
Genetic defect in thyroid hormonogenesis 1
Iodine accumulation, transport or trapping defect
A disorder characterized by the inability of the thyroid to maintain a concentration difference of readily exchangeable iodine between the plasma and the thyroid gland, leading to congenital hypothyroidism.
Congenital hypothyroidism due to dyshormonogenesis type 2A
Genetic defect in thyroid hormonogenesis 2A
A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.
Congenital hypothyroidism due to dyshormonogenesis type 3
Genetic defect in thyroid hormonogenesis type 3
A disorder due to thyroid dyshormonogenesis, causing large goiters of elastic and soft consistency in the majority of patients. Although the degree of thyroid dysfunction varies considerably among patients with defective thyroglobulin synthesis, patients usually have a relatively high serum free triiodothyronine (T3) concentration with disproportionately low free tetraiodothyronine (T4) level. The maintenance of relatively high free T3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases.
Congenital hypothyroidism due to dyshormonogenesis type 4
Genetic defect in thyroid hormonogenesis type 4
A disorder due to thyroid dyshormonogenesis, causing severe hypothyroidism, goiter, excessive levels of iodotyrosine in serum and urine, and variable mental deficits derived from unrecognized and untreated hypothyroidism.
Congenital hypothyroidism due to dyshormonogenesis type 5
Genetic defect in thyroid hormonogenesis type 5
A disorder due to thyroid dyshormonogenesis, causing hypothyroidism, goiter, and variable mental deficits derived from unrecognized and untreated hypothyroidism.
Congenital hypothyroidism due to dyshormonogenesis type 6
Genetic defect in thyroid hormonogenesis 6
A disorder due to a defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.
A disorder associated with a reduction in type II iodothyronine deiodinase activity.
An autosomal dominant disorder characterized by slightly increased thyroid-stimulating hormone levels, and elevated serum reverse triiodothyronine (rT3) levels and rT3/T3 ratios.
Thyroid hormone resistance, generalized, autosomal dominant
Familial euthyroid hyperthyroxinemia, secondary to pituitary and peripheral resistance to thyroid hormones
An autosomal dominant disease characterized by high levels of circulating thyroid hormones (T3-T4), goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. Patients have normal or slightly elevated thyroid stimulating hormone (TSH).
Thyroid hormone resistance, generalized, autosomal recessive
An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone.
Thyrotoxic hypokalemic periodic paralysis
A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease.
An autosomal dominant disorder characterized by generalized hypopigmentation and congenital, bilateral, profound sensorineural deafness.
Disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.
A clonal disorder characterized by the polyagglutination of red blood cells by naturally occurring anti-Tn antibodies following exposure of the Tn antigen on the surface of erythrocytes. Only a subset of red cells express the antigen, which can also be expressed on platelets and leukocytes. This condition may occur in healthy individuals who manifest asymptomatic anemia, leukopenia, or thrombocytopenia. However, there is also an association between the Tn antigen and leukemia or myelodysplastic disorders.
Toe syndactyly, telecanthus, and anogenital and renal malformations
Syndactyly with renal and anogenital malformations
A syndrome characterized by anal, genital and renal tract anomalies, facial dysmorphism and syndactyly. Features include anal stenosis, a rectovaginal fistula, clitoral hypertrophy, a pelvic right kidney, toe syndactyly, and telecanthus.
Intellectual developmental disorder with behavioral abnormalities and variable bone defects
An autosomal dominant disorder characterized by mildly to moderately impaired intellectual development and behavioral problems, such as autism, attention deficit and hyperactivity disorder, and aggressive episodes. Highly variable, additional features include osteochondroma, craniosynostosis, dysmorphic facies, arachnodactyly, and large head circumference.
An X-linked recessive disorder characterized by global developmental delay apparent from early infancy, impaired intellectual development, speech delay, behavioral abnormalities, abnormal gait, dysmorphic facial features, limb anomalies, and urogenital abnormalities with hypogenitalism. A subset of more severely affected males develop congenital diaphragmatic hernia in utero, which may result in perinatal or premature death. Carrier females may have very mild skeletal or hormonal abnormalities.
Absence of second premolars and third molars
Hypodontia/oligodontia with orofacial cleft
Selective tooth agenesis with orofacial cleft
A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG1 can be associated with orofacial cleft in some patients.
A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG10 inheritance is autosomal recessive.
A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth).
Tooth agenesis, selective, 4, with or without ectodermal dysplasia
A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). In STHAG4, the upper lateral incisors are absent or peg-shaped. Some STHAG4 patients manifest mild features of ectodermal dysplasia, including sparse hair, sparse eyebrows, short eyelashes, abnormalities of the nails, sweating anomalies and dry skin. STHAG4 inheritance is autosomal dominant or autosomal recessive.
An autosomal dominant form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth).
A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG8 inheritance is autosomal dominant.
A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG9 inheritance is autosomal dominant.
Retinal hemorrhage with vascular tortuosity
A disease characterized by marked tortuosity of second- and third-order retinal arteries with normal first-order arteries and venous system. Most patients manifest variable degrees of symptomatic transient vision loss due to retinal hemorrhage following minor stress or trauma.
Rare congenital heart disease (CHD) in which the pulmonary veins fail to connect to the left atrium during cardiac development, draining instead into either the right atrium or one of its venous tributaries. This disease accounts for 1.5% of all CHDs and has a prevalence of approximately 1 out of 15'000 live births.
Anus, imperforate, with hand, foot, and ear anomalies
Deafness, sensorineural, with imperforate anus and thumb anomalies
Townes-Brocks branchiootorenal-like syndrome
A form of Townes-Brocks syndrome, a rare autosomal dominant disease characterized by the triad of imperforate anus, dysplastic ears, and thumb malformations. Minor features of the condition include hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease.
An inborn error of the pentose phosphate pathway resulting in early-onset multisystem disease. Clinical features include growth retardation, dysmorphic features, cutis laxa, congenital heart disease, hepatosplenomegaly, telangiectases of the skin, pancytopenia, and bleeding tendency.
Transient bullous dermolysis of the newborn
Epidermolysis bullosa dystrophica dominant neonatal type
TBDN is a neonatal form of dystrophic epidermolysis bullosa characterized by sub-epidermal blisters, reduced or abnormal anchoring fibrils at the dermo-epidermal junction, and electron-dense inclusions in keratinocytes. TBDN heals spontaneously or strongly improves within the first months and years of life.
Transient familial neonatal hyperbilirubinemia
A condition characterized by excessive concentration of bilirubin in the blood, which may lead to jaundice. Breast milk jaundice is a common problem in nursing infants.
Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. Transient neonatal diabetes remits early, with a possible relapse during adolescence.
Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. In a significant number of patients with transient neonatal diabetes mellitus, diabetes type 2 appears later in life. The onset and severity of TNDM3 is variable with childhood-onset diabetes, gestational diabetes or adult-onset diabetes described.
Transposition of the great arteries dextro-looped 1
A congenital heart defect consisting of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. The presence or absence of associated cardiac anomalies defines the clinical presentation and surgical management of patients with transposition of the great arteries.
A form of Treacher Collins syndrome, a disorder of craniofacial development. Treacher Collins syndrome is characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss.
Mandibulofacial dysostosis Treacher Collins type autosomal recessive
A form of Treacher Collins syndrome, a disorder of craniofacial development. Treacher Collins syndrome is characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. TCS4 inheritance pattern is autosomal dominant.
An autosomal recessive condition characterized by the inability to digest trehalose, a disaccharide found in mushrooms, products containing baker's yeast, and dried food. Individuals with trehalase deficiency suffer from abdominal pain, increased rectal flatulence, and diarrhea due to osmotic water flow into the colon.
A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant.
A form of essential tremor, a common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles may also be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. ETM6 inheritance is autosomal dominant.
Autosomal dominant disorder characterized by craniofacial and skeletal abnormalities. It is allelic with tricho-rhino-phalangeal type 3. Typical features include sparse scalp hair, a bulbous tip of the nose, protruding ears, a long flat philtrum and a thin upper vermilion border. Skeletal defects include cone-shaped epiphyses at the phalanges, hip malformations and short stature.
A syndrome that combines the clinical features of tricho-rhino-phalangeal syndrome type 1 and multiple exostoses type 1. Affected individuals manifest multiple dysmorphic facial features including large, laterally protruding ears, a bulbous nose, an elongated upper lip, as well as sparse scalp hair, winged scapulae, multiple cartilaginous exostoses, redundant skin, and intellectual disability.
Autosomal dominant disorder characterized by craniofacial and skeletal abnormalities. It is allelic with tricho-rhino-phalangeal type 1. In TRPS3 a more severe brachydactyly and growth retardation are observed.
An autosomal dominant disease characterized by curly kinky hair at birth, enamel hypoplasia, taurodontism, thickening of cortical bones and variable expression of craniofacial morphology.
Fatal infantile diarrhea with trichorrhexis nodosa
Intractable diarrhea with phenotypic anomalies
A syndrome characterized by intrauterine growth retardation, severe diarrhea in infancy requiring total parenteral nutrition, facial dysmorphism, immunodeficiency, and hair abnormalities, mostly trichorrhexis nodosa. Hepatic involvement contributes to the poor prognosis of affected patients.
An autosomal recessive complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and global developmental delay.
A morphologic trait characterized by unusually long eyelashes and mild hypertrichosis of eyebrows. It can be observed in association with corneal irritation, cataracts, and hereditary spherocytosis.
Ichthyosiform erythroderma with hair abnormality and mental and growth retardation
Ichthyosis, congenital, with trichothiodystrophy
Ichthyosis with brittle hair, intellectual impairment, decreased fertility and short stature
Trichothiodystrophy with congenital ichthyosis
A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD1 patients manifest cutaneous photosensitivity.
A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder.
Trichothiodystrophy, complementation group A
Trichothiodystrophy 4, non-photosensitive
Trichothiodystrophy, nonphotosensitive 1
Trichothiodystrophy-neurocutaneous syndrome
Trichothiodystrophy non-photosensitive 1
A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD4 patients do not manifest cutaneous photosensitivity.
Trichothiodystrophy 5, non-photosensitive
An X-linked form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD5 features include microcephaly, profound intellectual disability, sparse brittle hair, aged appearance, short stature, facial dysmorphism, seizures, an immunoglobulin deficiency, multiple endocrine abnormalities, cerebellar hypoplasia and partial absence of the corpus callosum, in the absence of cellular photosensitivity and ichthyosis.
Trichothiodystrophy 6, non-photosensitive
A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD6 patients do not manifest cutaneous photosensitivity. Inheritance pattern has been reported to be autosomal recessive.
Trichothiodystrophy 7, non-photosensitive
A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD7 patients do not manifest cutaneous photosensitivity. They have cysteine- and threonine-deficient hair with alternating light and dark 'tiger-tail' banding pattern observed under polarization microscopy. Inheritance pattern is autosomal recessive.
Trichothiodystrophy 8, non-photosensitive
Trichothiodystrophy 8, nonphotosensitive
A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD8 is an autosomal recessive, non-photosensitive form characterized by brittle hair and nails, scaly skin, accompanied by failure to thrive, microcephaly, and neuromotor developmental delay.
Trichothiodystrophy 9, non-photosensitive
A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD9 is an autosomal recessive, non-photosensitive form characterized by brittle hair and nails, scaly skin, accompanied by failure to thrive, microcephaly, and neuromotor developmental delay.
A neuropsychiatric disorder characterized by chronic, repetitive, or compulsive hair pulling resulting in noticeable hair loss. Affected individuals may develop physical complications and often have overlapping psychological disorders, such as Gilles de la Tourette syndrome or obsessive-compulsive disorder.
A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head.
Inborn error of metabolism associated with an offensive body odor and caused by deficiency of FMO-mediated N-oxidation of amino-trimethylamine (TMA) derived from foodstuffs. Affected individuals excrete relatively large amounts of TMA in their urine, sweat, and breath, and exhibit a fishy body odor characteristic of the malodorous free amine.
Triokinase and FMN cyclase deficiency syndrome
An autosomal recessive disease characterized by cataracts and developmental delay that may be associated with cerebellar hypoplasia. Additional features may include liver dysfunction, microcytic anemia, and fatal cardiomyopathy with lactic acidosis following a febrile illness.
Hemolytic anemia due to triosephosphate isomerase deficiency
An autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, progressive neuromuscular dysfunction, susceptibility to bacterial infection, and cardiomyopathy.
Triphalangeal thumb-polysyndactyly syndrome
Autosomal dominant syndrome. It is characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development.
A disorder of vision characterized by a selective deficiency of blue spectral sensitivity.
Idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer.
An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes.
Tubulointerstitial kidney disease, autosomal dominant, 1
Familial juvenile hyperuricemic nephropathy 1
Glomerulocystic kidney disease with hyperuricemia and isosthenuria
A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance.
Tubulointerstitial kidney disease, autosomal dominant, 2
Autosomal dominant medullary cystic kidney disease 1
Tubulointerstitial kidney disease, autosomal dominant, 4
Early-onset hyperuricemia anemia and progressive kidney failure
Familial juvenile hyperuricemic nephropathy 2
Tubulointerstitial kidney disease, autosomal dominant, 5
Familial juvenile hyperuricemic nephropathy 4
Hyperuricemic nephropathy, familial juvenile, 4
An autosomal dominant condition characterized by predisposition to develop a variety of tumors, including benign melanocytic tumors as well as several malignant tumors, including uveal melanoma, cutaneous melanoma, malignant mesothelioma on exposure to asbestos, lung adenocarcinoma and meningioma.
An autosomal recessive condition characterized by predisposition to develop a variety of tumors or malignancies, including acute myeloid leukemia, myelodysplastic syndrome, colorectal adenomatous polyposis and carcinoma, and uveal melanoma.
Tumoral calcinosis, hyperphosphatemic, familial, 1
Cortical hyperostosis with hyperphosphatemia
Familial tumoral calcinosis with hyperphosphatemia
Tumoral calcinosis primary hyperphosphatemic
A form of hyperphosphatemic tumoral calcinosis, a rare autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients have recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement.
Tumoral calcinosis, hyperphosphatemic, familial, 2
Tumoral calcinosis, hyperphosphatemic, familial, 3
Tumoral calcinosis, normophosphatemic, familial
Tumoral calcinosis with normophosphatemia
An uncommon, life-threatening disorder characterized by progressive deposition of calcified masses in cutaneous and subcutaneous tissues. Serum phosphate levels are normal. Clinical features include painful calcified ulcerative lesions and massive calcium deposition in the mid- and lower dermis, severe skin and bone infections, erythematous papular skin eruption in infancy, conjunctivitis, and gingivitis. NFTC shows a striking resemblance to acquired dystrophic calcinosis, in which tissue calcification occurs as a consequence of tissue injury/inflammation.
A syndrome characterized by facial dysmorphism, intellectual disability, feeding problems, impaired growth, and a range of brain, cardiovascular, and skeletal abnormalities. Craniofacial features include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic ears.
Keratosis palmaris et plantaris with esophageal cancer
An autosomal dominant syndrome characterized by diffuse palmoplantar keratoderma, oral leukokeratosis, and a high lifetime risk of esophageal cancer.
A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Diabetes mellitus, insulin-dependent, 10
Diabetes mellitus, insulin-dependent, 12
Diabetes mellitus, insulin-dependent, 19
Diabetes mellitus, insulin-dependent, 20
Diabetes mellitus, insulin-dependent, 22
A form of diabetes mellitus, a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Diabetes mellitus, non-insulin-dependent, 1
Diabetes mellitus, non-insulin-dependent, 5
Type IIb congenital disorder of glycosylation
Characterized by marked generalized hypotonia and hypomotility of the neonate, dysmorphic features, including a prominent occiput, short palpebral fissures, retrognathia, high arched palate, generalized edema, and hypoplastic genitalia. Symptoms of the infant included hepatomegaly, hypoventilation, feeding problems and seizures. The clinical course was progressive and the infant did not survive more than a few months.
An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and hepatorenal manifestations. Typical features include hepatic necrosis, renal tubular injury, episodic weakness, self-mutilation, and seizures. Renal tubular dysfunction is associated with phosphate loss and hypophosphataemic rickets. Progressive liver disease can lead to the development of hepatocellular carcinoma. Dietary treatment with restriction of tyrosine and phenylalanine alleviates the rickets, but liver transplantation has so far been the only definite treatment.
Keratosis palmoplantaris with corneal dystrophy
An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and intellectual disability.
4-hydroxyphenylpyruvate dioxygenase deficiency
4-hydroxyphenylpyruvic acid oxidase deficiency
An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild intellectual disability.
Ubiquitin-positive frontotemporal dementia
Tau-negative frontotemporal dementia linked to chromosome 17
Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.
Muscular dystrophy, limb-girdle, autosomal recessive 22
A congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.
A form of Ullrich muscular dystrophy, a congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.
Characterized by ulnar ray defects, obesity, hypogenitalism, delayed puberty, hypoplasia of nipples and apocrine glands.
A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age. UHS1 inheritance is autosomal dominant.
A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age.
UPVN is characterized by a localized epidermolytic hyperkeratosis in parts of the right palm and the right sole, following the lines of Blaschko.
Cutis laxa with severe pulmonary gastrointestinal and urinary abnormalities
A syndrome characterized by disrupted pulmonary, gastrointestinal, urinary, musculoskeletal, craniofacial and dermal development. Clinical features include cutis laxa, mild cardiovascular lesions, respiratory distress with cystic and atelectatic changes in the lungs, and diverticulosis, tortuosity and stenosis at various levels of the intestinal tract. Craniofacial features include microretrognathia, flat midface, receding forehead and wide fontanelles.
A form of nephrolithiasis, a common multifactorial disease characterized by stones formation in the kidney and urinary tract. Nephrolithiasis is due to supersaturation of the urine by stone-forming constituents, including calcium, oxalate and uric acid. Crystals or foreign bodies can act as nidi, upon which ions from the supersaturated urine form microscopic crystalline structures. Uric acid nephrolithiasis occurs when the urine becomes overly concentrated with uric acid and accounts for 20% of all stones.
An autosomal recessive inborn error of metabolism characterized by increased urinary uridine and cytidine excretion. It is a likely benign metabolic trait without clinical manifestations.
Encephalopathy due to urocanase deficiency
An inborn error of histidine metabolism resulting in urocanic aciduria and neurological manifestations including intellectual disability, ataxia, episodic aggressive behavior or exaggerated affection-seeking.
Hydronephrosis with peculiar facial expression
Inverted smile and occult neuropathic bladder
Partial facial palsy partial with urinary abnormalities
A rare autosomal recessive disorder characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. Affected individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure.
Uruguay faciocardiomusculoskeletal syndrome
Faciocardiomusculoskeletal syndrome, Uruguay type
An X-linked recessive syndrome characterized by brachyturricephaly, pugilistic coarse facies, a muffled voice, cardiomyopathy, muscular hypertrophy, broad hands, wide feet with progressive pes cavus deformities, dislocation of toes, variable congenital hip dislocation, and scoliosis.
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
USH1DF patients are heterozygous for mutations in CDH23 and PCDH15, indicating a digenic inheritance pattern.
A form of Usher syndrome, a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1M is an autosomal recessive disease characterized by prelingual sensorineural hearing loss, vestibular dysfunction, night blindness, and progressive impairment of vision.
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses.
Usher syndrome type IIC GPR98/PDZD7 digenic
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses.
USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life.
A syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life.
A form of Usher syndrome, a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish different types of Usher syndrome. USH4 is characterized by late onset of retinitis pigmentosa and usually late-onset of progressive sensorineural hearing loss without vestibular involvement. USH4 inheritance is autosomal recessive.
Usmani-Riazuddin syndrome, autosomal dominant
A neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development and speech delay, hypotonia, and behavioral abnormalities. More variable additional features may include seizures and distal limb anomalies.
Usmani-Riazuddin syndrome, autosomal recessive
A neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development and speech delay, hypotonia, spasticity, and behavioral abnormalities. More variable additional features may include seizures, scoliosis, and joint laxity.
An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors.
An autosomal recessive disorder characterized by cutaneous photosensitivity and slight dyspigmentation, without an increased risk of skin tumors.
VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects.
VACTERL association X-linked with or without hydrocephalus
Vertebral anal tracheoesophageal esophageal radial anomalies
A syndrome characterized by a non-random association of congenital defects. Affected individuals manifest vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) such as urethral atresia with hydronephrosis, and limb anomalies (L) such as hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb. Some patients may have hydrocephalus. Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement.
Endosteal hyperostosis autosomal recessive
VBCH is an autosomal recessive sclerosing bone dysplasia characterized by endosteal hyperostosis of the mandible, skull, ribs, clavicles, and diaphyses of the long bones. Affected patients present a symmetrically increased thickness of bones, most frequently found as an enlarged jawbone, but also an enlargement of the skull, ribs, diaphysis of long bones, as well as tubular bones of hands and feet. The clinical consequence of increased thickness of the skull include facial nerve palsy causing hearing loss, visual problems, neurological pain, and, very rarely, blindness as a consequence of optic atrophy. Serum alkaline phosphatase levels are elevated.
VBCH2 is an autosomal dominant sclerosing bone dysplasia characterized by cranial osteosclerosis, thickened calvaria and cortices of long bones, enlarged mandible and normal serum alkaline phosphatase levels.
Blepharophimosis arachnodactyly and congenital contractures
Marden-Walker-like syndrome without psychomotor retardation
A syndrome characterized by craniofacial and skeletal abnormalities that include blepharophimosis, a flat and wide nasal bridge, narrow and beaked nose, hypoplastic maxilla with or without cleft palate and everted lower lip, prominent ears, down-slanting eyes, arachnodactyly, and camptodactyly. Patients present congenital joint contractures that improve without intervention, and normal growth and development. Intelligence is normal. Rarely, enlarged cerebella can be present. Some patients experience respiratory problems due to laryngeal abnormalities.
Cleft lip and/or palate with mucous cysts of lower lip
An autosomal dominant developmental disorder characterized by lower lip pits, cleft lip and/or cleft palate.
An X-linked recessive syndrome characterized by different degrees of intellectual disability, moderate to severe short stature, microcephaly, hypogonadism, and variable congenital malformations.
An autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia.
A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Variegate porphyria is the most common form of porphyria in South Africa. It is characterized by skin hyperpigmentation and hypertrichosis, abdominal pain, tachycardia, hypertension and neuromuscular disturbances. High fecal levels of protoporphyrin and coproporphyrin, increased urine uroporphyrins and iron overload are typical markers of the disease.
Vascular malformation, primary intraosseous
An autosomal recessive, rare malformation characterized by non-neoplastic severe expansions of blood vessels, usually seen in the vertebral column and in the skull. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequently observed.
Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome
An autosomal recessive, systemic necrotizing vasculitis that affects medium and small arteries. The ensuing tissue ischemia can affect any organ, including the skin, musculoskeletal system, kidneys, gastrointestinal tract, and the cardiovascular and nervous systems. Organ involvement and disease severity are highly variable. Clinical features include recurrent ischemic stroke affecting the small vessels of the brain and resulting in neurologic dysfunction, recurrent fever, myalgias, livedoid rash, gastrointestinal pain and hepatosplenomegaly.
Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations
Hereditary endotheliopathy with retinopathy-nephropathy-stroke
Vascular retinopathy with cerebral and renal involvement and Raynaud and migraine phenomena
An adult-onset, autosomal dominant endotheliopathy affecting the microvessels of the brain. It results in central nervous system degeneration and retinopathy, with progressive loss of vision, stroke, motor impairment, and cognitive decline. The ocular manifestations are characterized by telangiectasias, microaneurysms and retinal capillary obliteration starting in the macula. Diseased cerebral white matter has prominent small infarcts that often coalesce to pseudotumors. A subset of patients have systemic vascular involvement that can manifest as Raynaud phenomenon, micronodular cirrhosis, and glomerular dysfunction.
A syndrome characterized by abnormal pharyngeal arch development that results in defective development of the parathyroid glands, thymus, and conotruncal region of the heart. The phenotype is highly variable, with no single clinical feature present in every patient. Affected individuals may present with structural or functional palatal abnormalities, cardiac defects, unique facial characteristics, hypernasal speech, hypotonia, and defective thymic development associated with impaired immune function. In addition, affected individuals may present with learning disabilities, overt developmental delay, and psychiatric disorders.
Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome
RYR2 calcium release deficiency syndrome
An autosomal dominant arrhythmogenic disorder characterized by syncope, cardiac arrest and/or sudden unexpected death, often in association with physical exertion or acute emotional stress. Patients who survive manifest polymorphic ventricular tachycardia and ventricular fibrillation. Unlike typical catecholaminergic ventricular tachycardia, arrhythmias are not reproducible on exercise stress testing or adrenaline challenge.
A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death.
Ventricular tachycardia, catecholaminergic polymorphic, 1, with or without atrial dysfunction and/or dilated cardiomyopathy
Double tachycardia induced by catecholamines
Malignant paroxysmal ventricular tachycardia
Stress-induced polymorphic ventricular tachycardia
Ventricular tachycardia catecholaminergic polymorphic 1
An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT1 inheritance is autosomal dominant.
Ventricular tachycardia, catecholaminergic polymorphic, 2
An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT2 inheritance is autosomal recessive.
Ventricular tachycardia, catecholaminergic polymorphic, 3
An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, or sudden death after physical activity or emotional stress. CPVT3 is an autosomal recessive disorder with onset at early age and associated with sudden death in childhood. Patients manifest QT prolongation on adrenergic stimulation.
Ventricular tachycardia, catecholaminergic polymorphic, 4
An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT4 inheritance is autosomal dominant.
Ventricular tachycardia, catecholaminergic polymorphic, 6
An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT6 inheritance is autosomal dominant.
An autosomal recessive disorder with fatal outcome, characterized by prenatal onset of severe features including limb contractures, arthrogryposis, and enlarged brain ventricles that may be associated with hydrocephalus, abnormalities of the corpus callosum, and cerebellar hypoplasia. Some affected fetuses may also have congenital heart disease and hydrops fetalis. Death occurs in utero.
Ventriculomegaly with cystic kidney disease
A severe autosomal recessive developmental disorder manifesting in utero. It is characterized by cerebral ventriculomegaly, echogenic kidneys, microscopic renal tubular cysts and findings of congenital nephrosis.
A syndrome characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects.
Vertebral anomalies and variable endocrine and T-cell dysfunction
An autosomal dominant syndrome characterized by skeletal malformations primarily involving the vertebrae, immunodeficiency, endocrine abnormalities such as hypoparathyroidism and growth hormone deficiency, craniofacial dysmorphism, congenital cardiac anomalies consisting of double-outlet right ventricle, pulmonary valve stenosis and atrial septal defect, and developmental impairments.
Vertebral hypersegmentation and orofacial anomalies
An autosomal dominant disease characterized by supernumerary ribs, supernumerary cervical, thoracic and/or lumbar vertebrae, and orofacial anomalies such as cleft lip with or without cleft palate in most patients.
Vertebral, cardiac, renal, and limb defects syndrome 1
An autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects.
Vertebral, cardiac, renal, and limb defects syndrome 2
Vertebral, cardiac, renal, and limb defects syndrome 3
An autosomal recessive, lethal disorder characterized by severe cardiac and renal anomalies, including hypoplastic or absent left ventricle, transposition of the great arteries, absent pulmonary trunk, and hypoplastic or absent kidneys. Patients also exhibit vertebral segmentation defects and shortening of the proximal long bones or micromelia. Death occurs in early infancy.
Vertebral, cardiac, tracheoesophageal, renal, and limb defects
An autosomal dominant disorder with incomplete penetrance and variable expressivity, characterized by cardiac, vertebral, tracheo-esophageal, renal and limb defects. Some patients also exhibit craniofacial abnormalities.
A rare malformation characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence.
An autosomal dominant disorder characterized by mild developmental delay and intellectual disability, speech delay, learning difficulties, autistic features, and mild facial dysmorphism.
A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease.
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic
A sporadic, often fatal, treatment-refractory inflammatory syndrome that develops in late adulthood. Clinical features include fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. The disease affects only males and is associated with de novo somatic mutations.
An autosomal dominant disorder characterized by localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum.
Immunodeficiency with cleft lip/palate cataract hypopigmentation and absent corpus callosum
A rare congenital multisystem disorder characterized by agenesis of the corpus callosum, cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy.
An autosomal dominant form of myopathic pseudo-obstruction characterized by impaired function of enteric smooth muscle cells, resulting in abnormal intestinal motility, severe abdominal pain, malnutrition, and even death. The disease shows inter- and intrafamilial variability. Most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and dependence on total parenteral nutrition and urinary catheterization.
A form of visceral myopathy, a gastrointestinal pseudo-obstruction disorder characterized by impaired function of enteric smooth muscle cells, intestinal dysmotility and paresis, severe abdominal pain, and malnutrition. The disease shows inter- and intrafamilial variability. VSCM2 inheritance is autosomal dominant.
Visceral neuropathy, familial, 1, autosomal recessive
An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Additional variable features are progressive peripheral neuropathy, arthrogryposis, hypoplasia or aplasia of the olfactory bulb and of the external auditory canals, microtia or anotia, and facial dysmorphism. Some patients present structural cardiac anomalies and arthrogryposis with multiple pterygia.
Visceral neuropathy, familial, 2, autosomal recessive
An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Patients also show peripheral axonal neuropathy, hypotonia, mild developmental delay, unilateral ptosis, and sensorineural hearing loss.
An autosomal recessive disease characterized by early-onset thoracic aortic aneurysm, aneurysm and tortuosity of other arteries, motor developmental delay, connective tissue findings such as joint hypermobility, skin laxity and hernias, and craniofacial dysmorphic features. Immune dysregulation has been reported in some patients.
An autosomal dominant disorder characterized by global developmental delay, intellectual disability of varying degree, speech delay, motor delay, and hypotonia. Abnormal growth, and cerebral, skeletal, muscle and soft tissue abnormalities are frequently observed. Many patients have behavioral problems, including anxiety, obsessive compulsive disorder, autism spectrum disorder and attention-deficit hyperactivity disorder.
Visual impairment and progressive phthisis bulbi
An autosomal recessive, progressive disease characterized by poor vision at birth and development of bilateral phthisis bulbi by adulthood.
An autosomal dominant disorder of vitamin D metabolism resulting in early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D.
A pigmentary disorder of the skin and mucous membranes. It is characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases.
Vitiligo-associated multiple autoimmune disease 1
Systemic lupus erythematosus vitiligo-related
A disorder characterized by the association of vitiligo with several autoimmune and autoinflammatory diseases including autoimmune thyroid disease, rheumatoid arthritis and systemic lupus erythematosus.
Vitreoretinochoroidopathy, autosomal dominant
Vitreoretinochoroidopathy autosomal dominant with nanophthalmos, microcornea, rod-cone dystrophy, cataract and posterior staphyloma
Vitreoretinochoroidopathy with microcornea-glaucoma-cataract
An autosomal dominant ocular disorder characterized by vitreoretinochoroidal dystrophy. The clinical presentation is variable. VRCP may be associated with cataract, nanophthalmos, microcornea, shallow anterior chamber, and glaucoma.
Vitreoretinopathy with phalangeal epiphyseal dysplasia
An autosomal dominant disorder characterized by rhegmatogenous retinal detachment, premature arthropathy, and development of phalangeal epiphyseal dysplasia resulting in brachydactyly.
Autosomal dominant familial exudative vitreoretinopathy
A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history.
X-linked familial exudative vitreoretinopathy
A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.
A form of exudative vitreoretinopathy, a disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.
Vitreoretinopathy, neovascular inflammatory
Neovascular inflammatory vitreoretinopathy autosomal dominant
An autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. Patients present during the second or third decade of life with posterior uveitis and reduction of the electroretinogram b-wave. They become more symptomatic when cataracts, cystoid macular edema, and disk edema diminish visual acuity during the second stage. Severe vision loss begins during the third stage when proliferative retinal neovascularization and epiretinal membranes appear. There is an ongoing pigmentary retinal degeneration and peripheral visual field loss during all stages. In the fourth stage, proliferative vitreoretinopathy causes tractional retinal detachments at the macula and vitreous base. The fifth or end-stage disease is marked by phthisis.
Congenital deafness with keratopachydermia and constrictions of fingers and toes
An autosomal dominant disease characterized by hyperkeratosis, constriction on fingers and toes and congenital deafness.
A variant form of Vohwinkel syndrome without hearing loss and associated with ichthyosiform dermatosis. Clinical features include palmoplantar keratoderma, pseudoainhum and ichthyosis. Compact hyperkeratosis with round retained nuclei and hypergranulosis is observed on skin biopsies.
VHLD is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst).
A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.
A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in altered platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.
A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.
Intellectual developmental disorder with impaired expressive speech and behavioral abnormalities, with or without seizures
An autosomal dominant disorder characterized by intellectual disability, poor speech, motor delay, and autistic features. Most patients have additional non-specific features, including hypotonia and gait abnormalities, seizures, which may be refractory, high pain threshold, and sleep disturbances.
WS1 is an autosomal dominant disorder characterized by non-progressive sensorineural deafness, pigmentary disturbances such as frontal white blaze of hair, heterochromia of irides, white eyelashes, leukoderma, and wide bridge of nose owing to lateral displacement of the inner canthus of each eye (dystopia canthorum). WS1 shows variable clinical expression and some affected individuals do not manifest hearing impairment or iris pigmentation disturbances. Dystopia canthorum is the most consistent sign and is found in 98% of the patients.
WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1.
Hypogonadotropic hypogonadism with anosmia and deafness with or without hypopigmentation
Kallmann syndrome and deafness with or without hypopigmentation
Waardenburg syndrome type 2E with or without neurologic involvement
WS2E with or without neurologic involvement
An autosomal dominant auditory-pigmentary disorder characterized by sensorineural deafness, pigmentary disturbances of the hair, skin and eyes, and absence of dystopia canthorum which is the lateral displacement of the inner canthus of each eye. Individuals with WS2E may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Some patients can manifest features of Kallmann syndrome.
A form of Waardenburg syndrome, an auditory-pigmentary disorder characterized by sensorineural deafness, pigmentary disturbances of the hair, skin and eyes, and absence of dystopia canthorum which is the lateral displacement of the inner canthus of each eye. WS2F is an autosomal recessive form with variable expressivity, characterized by congenital or neonatal-onset sensorineural hearing loss.
Waardenburg syndrome with upper limb anomalies
WS3 is an autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, dystopia canthorum and limb anomalies such as hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, syndactylies.
Hirschsprung disease with pigmentary anomaly
Waardenburg syndrome with Hirschsprung disease type 4A
A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease).
Waardenburg syndrome with Hirschsprung disease type 4B
Waardenburg syndrome with Hirschsprung disease type 4C
A rare vitreoretinopathy characterized by an optically empty vitreous cavity with fibrillary condensations and a preretinal avascular membrane. Other optical features include progressive chorioretinal atrophy, perivascular sheating, subcapsular cataract and myopia.
A neurologic disorder characterized by delayed psychomotor development, intellectual disability, and early-onset Parkinson disease.
A rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism.
A rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism.
A form of Warburg micro syndrome, a rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism.
An autosomal dominant disease characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acro-osteolysis.
A condition characterized by sensitivity to warfarin, a drugs used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. Warfarin sensitive individuals develop bleeding complications when they are given warfarin within the therapeutic ranges.
A syndrome characterized by severe microcephaly, pre- and postnatal growth retardation, facial dysmorphism and abnormal skin pigmentation. Additional features include high arched palate, coloboma of the right optic disk, deafness, ventricular septal defect, toes and fingers abnormalities. At cellular level, drug-induced chromosomal breakage, a feature of Fanconi anemia, and sister chromatid cohesion defects, a feature of Roberts syndrome, coexist.
Pulmonary stenosis with cafe-au-lait spots
A syndrome characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and intellectual disability. It is considered as an atypical form of neurofibromatosis.
A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand.
Hypothalamo-pituitary-frontotemporal hypoplasia with visual and renal anomalies
A disorder characterized by postnatal microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, global developmental delay, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract.
Autosomal recessive Weill-Marchesani syndrome
Congenital mesodermal dysmorphodystrophy
A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma.
Autosomal dominant Weill-Marchesani syndrome
Glaucoma-lens ectopia-microspherophakia-stiffness-shortness syndrome
An autosomal recessive syndrome characterized by lenticular myopia, ectopia lentis, glaucoma, spherophakia and short stature. Brachydactyly and decreased joint flexibility are present in some patients.
An autosomal dominant, multiple congenital anomaly syndrome with variable expressivity and complete penetrance. Patients manifest developmental delay, hypotonia, feeding difficulties, craniofacial abnormalities including ptosis, abnormal head shape, downslanting palpebral fissures, metopic ridging, and craniosynostosis. Variable congenital heart defects can be observed in some patients. A few patients show agenesis of the corpus callosum on brain imaging.
Late-onset autosomal dominant distal muscular dystrophy
An autosomal dominant disorder characterized by adult onset of distal muscle weakness predominantly affecting the distal long extensors of the hands, with slow progression to involve all small hand muscles and the lower legs. Skeletal muscle biopsy shows myopathic changes and prominent rimmed vacuoles. Rare homozygous patients showed earlier onset, faster progression, and proximal muscle involvement.
A rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction.
Warts, hypogammaglobulinemia, infections and myelokathexis syndrome 1
An autosomal dominant immunologic disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.
Warts, hypogammaglobulinemia, infections, and myelokathexis 2
An autosomal recessive form of WHIM syndrome, a primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow. Monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. There is significant phenotypic variation among patients, such that some individuals may have an incomplete form of the disorder in which one or more of the classic tetrad features are not present.
A rare disorder characterized by the presence of soft, white, and spongy plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved.
Global developmental delay, hypotonia, and characteristic facial features
An autosomal dominant disorder characterized by global developmental delay, variably impaired intellectual development, hypotonia, and characteristic facial features. Some patients may have genitourinary and skeletal abnormalities.
An autosomal dominant syndrome characterized by developmental delay, intellectual disability, hypotonia, behavioral abnormalities, and dysmorphic facial features. Variable features include short stature, microcephaly, strabismus and hearing loss.
Contractures of feet, muscle atrophy, and oculomotor apraxia
Oculomotor apraxia with congenital contractures and muscle atrophy
A severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show intellectual disability. Carrier females may have mild features of the disorder.
Wieacker-Wolff syndrome, female-restricted
An X-linked dominant neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero resulting in fetal akinesia, arthrogryposis multiplex congenita and diffuse contractures apparent at birth, global developmental delay with difficulty walking or inability to walk, hypotonia, variably impaired intellectual development, poor or absent speech and language, and dysmorphic features.
An autosomal recessive, neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, hypotonia, variable mental impairment, and a progeroid appearance. Clinical features include apparent macrocephaly, sparse hair, prominent scalp veins, entropion, greatly widened anterior fontanelles, malar hypoplasia, and generalized lipoatrophy. Death usually occurs in early childhood but survival to third decade has been reported.
Hairy elbows short stature facial dysmorphism and developmental delay
Hypertrichosis cubiti facial dysmorphism and developmental delay
A syndrome characterized by hairy elbows (hypertrichosis cubiti), intellectual disability, a distinctive facial appearance, and short stature. Facial characteristics include long eyelashes, thick or arched eyebrows with a lateral flare, and downslanting and vertically narrow palpebral fissures.
Embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms.
A pediatric malignancy of kidney, and the most common childhood abdominal malignancy. It is caused by the uncontrolled multiplication of renal stem, stromal, and epithelial cells.
An autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.
A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes.
Eczema-thrombocytopenia-immunodeficiency syndrome
An X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.
An immunodeficiency disorder characterized by eczema, thrombocytopenia, recurrent infections, defective T-cell proliferation, and impaired natural killer cell function.
An autosomal dominant syndrome characterized by global developmental delay, mild to severe intellectual disability, and facial dysmorphism. Additional features include short stature, microcephaly, joint hypermotility, and small hands and feet with digital abnormalities. Brain imaging shows dilated ventricles, thin corpus callosum and, in some cases, dysgyria or polymicrogyria.
Multiple epiphyseal dysplasia with early-onset diabetes mellitus
A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, intellectual disability and cardiovascular abnormalities.
Ventricular familial preexcitation syndrome
A supernormal conduction disorder characterized by the presence of one or several accessory atrioventricular connections, which can lead to episodes of sporadic tachycardia.
Diabetes insipidus and mellitus with optic atrophy and deafness syndrome
A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses.
A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.
Wolfram-like syndrome autosomal dominant
Hearing loss progressive with optic atrophy and/or impaired glucose regulation
A disease characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy. The hearing impairment, which is usually diagnosed in the first decade of life, is relatively constant and alters mainly low- and middle-frequency ranges.
A severe manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. WD occurs in infancy and is nearly always fatal before the age of 1 year.
A rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, intellectual disability, and extrapyramidal syndrome.
A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrhexis nodosa and tapered ends.
Woolly hair autosomal recessive 1 with or without hypotrichosis
A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrhexis nodosa and tapered ends. Some individuals exhibit features of hypotrichosis.
Woolly hair autosomal recessive 2 with or without hypotrichosis
A hair shaft disorder characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, woolly hair grows slowly and stops growing after a few inches. Under light microscopy, woolly hair shows some structural anomalies, including trichorrhexis nodosa and tapered ends. Some individuals may present with hypotrichosis.
Woolly hair, autosomal recessive 3, with hypotrichosis
A rare autosomal recessive disorder characterized by wrinkling of the skin of the dorsum of the hands and feet, an increased number of palmar and plantar creases, wrinkled abdominal skin, multiple musculoskeletal abnormalities, microcephaly, growth failure and developmental delay.
Humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin.
Less severe form of X-linked immunodeficiency with a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.
X-linked dyserythropoietic anemia and thrombocytopenia
Disorder characterized by erythrocytes with abnormal size and shape, and paucity of platelets in peripheral blood. The bone marrow contains abundant and abnormally small megakaryocytes.
A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol.
Combined deficiency of xanthine dehydrogenase and aldehyde oxidase
A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. In addition, XAN2 patients cannot metabolize allopurinol into oxypurinol due to dual deficiency of xanthine dehydrogenase and aldehyde oxidase.
Xeroderma pigmentosum complementation group A
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-A patients show the most severe skin symptoms and progressive neurological disorders.
Xeroderma pigmentosum complementation group B
Xeroderma pigmentosum group B with Cockayne syndrome
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-B patients present features of Cockayne syndrome, including cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex.
Xeroderma pigmentosum complementation group C
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities.
Xeroderma pigmentosum complementation group D
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-D patients present features of Cockayne syndrome, including cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex.
Xeroderma pigmentosum complementation group E
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-E patients show a mild phenotype with minimal or no neurologic features.
Xeroderma pigmentosum complementation group F
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-F patients show a mild phenotype.
Xeroderma pigmentosum complementation group G
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-G patients present features of Cockayne syndrome, cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex.
Xeroderma pigmentosum type F/Cockayne syndrome
A variant form of Cockayne syndrome, a disorder characterized by growth retardation, microcephaly, impairment of nervous system development, pigmentary retinopathy, peculiar facies, and progeria together with abnormal skin photosensitivity. Cockayne syndrome dermatological features are milder than those in xeroderma pigmentosum and skin cancers are not found in affected individuals. XPF/CS patients, however, present with severe skin phenotypes, including severe photosensitivity, abnormal skin pigmentation, and skin cancer predisposition.
Xeroderma pigmentosum with normal DNA repair rates
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most patients with the variant type of xeroderma pigmentosum do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.
A syndrome characterized by aged bird-like facies, lack of subcutaneous fat, dwarfism, cachexia and microcephaly. Additional features include sun-sensitivity from birth, learning disabilities, hearing loss, and visual impairment.
An autosomal dominant disorder characterized by intellectual disability, mild dysmorphism, hypotonia, delayed psychomotor development with absent or poor expressive language, hypoplasia of the corpus callosum, simplified gyral pattern, and delayed myelination.
An autoinflammatory disease characterized by periodic fever, dermatitis, polyarthritis, leg swelling, and gastrointestinal and sicca-like symptoms. YAOS is a complex disease with multifactorial inheritance.
Yemenite deaf-blind hypopigmentation syndrome
A disorder characterized by cutaneous hypopigmented and hyperpigmented spots and patches, microcornea, coloboma and severe hearing loss.
An autosomal recessive disorder characterized by global developmental delay, and variably impaired intellectual development. Additional variable features may include hypotonia, spasticity, ataxia, hearing loss, visual problems, seizures, and non-specific anomalies on brain imaging.
A syndrome characterized by severe global developmental delay, intellectual disability, dysmorphic facial features, microcephaly, abnormal movements, congenital heart disease comprising developmental abnormalities of the great vessels, and abnormal auditory and visual function. The transmission pattern is consistent with autosomal recessive inheritance.
Cleidocranial dysplasia with micrognathia, absent thumbs, and distal aphalangia
A severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy.
An autosomal recessive disorder characterized by developmental delay, progressive microcephaly, and short stature, as well as dysmorphic features including sparse scalp hair, cupped ears, wide nose and mouth, short philtrum, and high-arched palate. Other variable features have been observed, including ocular, skeletal, cardiac, and renal anomalies.
Fibromatosis, gingival, with abnormal fingers, fingernails, nose, and ears, and splenomegaly
Gingival fibromatosis, abnormal fingers, fingernails, nose and ears and splenomegaly
A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some patients manifest intellectual disability with or without epilepsy. ZLS1 inheritance is autosomal dominant.
A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some patients manifest intellectual disability with or without epilepsy. ZLS2 inheritance is autosomal dominant.
A form of Zimmermann-Laband syndrome, a rare developmental disorder characterized by facial dysmorphism with bulbous nose and thick floppy ears, gingival enlargement, hypoplasia or aplasia of terminal phalanges and nails, hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some patients manifest intellectual disability with or without epilepsy. ZLS3 inheritance is autosomal dominant.
Neonatal zinc deficiency due to low breast milk zinc
A disorder occurring in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is required for normal growth particularly in infants, and breast milk normally contains adequate zinc to meet the requirement for infants up to 4 to 6 months of age. Zinc deficiency can lead to dermatitis, alopecia, decreased growth, and impaired immune function. The disorder shows autosomal dominant inheritance with incomplete penetrance.
An autosomal dominant syndrome characterized by intellectual disability, developmental delay, malformations of the cerebral cortex, epilepsy, vision problems, musculo-skeletal abnormalities, and congenital malformations.