900000000000509007: United States of America English language reference set (foundation metadata concept)

SNOMED CT Concept\SNOMED CT Model Component\Foundation metadata concept (foundation metadata concept)\Reference set\Language type reference set (foundation metadata concept)\English [International Organization for Standardization 639-1 code en] language reference set (foundation metadata concept)\US English

Status: current, Not sufficiently defined by necessary conditions definition status (core metadata concept). Date: 31-Jan 2002. Module: SNOMED CT model component module (core metadata concept)

Descriptions:

Expanded Value Set

Outbound Relationships	Type	Target	Active	Characteristic	Refinability	Group	Values
US English	Is a	English [International Organization for Standardization 639-1 code en] language reference set (foundation metadata concept)	true	Inferred relationship	Some

Members	acceptabilityId
A rare genetic isolated constitutional thrombocytopenia disease with characteristics of decreased platelet counts not associated with platelet morphology or function impairment, in multiple members of a family. Manifestations are variable, typically ranging from asymptomatic to mild bleeding diathesis (e.g. easy bruising, epistaxis, petechiae). Occasionally, a more severe bleeding tendency has been associated and a mild predisposition to infection and eczema has been reported.	Preferred (foundation metadata concept)
A rare genetic isolated constitutional thrombocytopenia disease with characteristics of impaired platelet aggregation resulting from a defect in thromboxane synthesis or signaling, manifesting with mild to moderate mucocutaneous, gastrointestinal or surgical bleeding (for example easy bruising, prolonged epistaxis, excessive bleeding after a tooth extraction). Conferred by heterozygous mutation in the gene encoding the thromboxane A2 receptor (TBXA2R) on chromosome 19p13.	Preferred (foundation metadata concept)
A rare genetic isolated diffuse palmoplantar keratoderma with characteristics of diffuse, mild to thick finely demarcated hyperkeratosis of palms and soles. Additional clinical findings include knuckle pad-like keratoses on fingers, hyperkeratosis of umbilicus and areola, diffuse dry skin, hyperhidrosis, hangnails and frequent fungal infections. Histological examination of lesions reveals orthokeratotic hyperkeratosis, acanthosis, hypergranulosis and mild lymphocyte infiltrations in the upper dermis with no evidence of epidermolysis.	Preferred (foundation metadata concept)
A rare genetic isolated dystonia initially presenting as torticollis and later progressing to segmental or generalized dystonia. Dysphonia and dysarthria also occur later in the disease course.	Preferred (foundation metadata concept)
A rare genetic isolated dystonia with characteristics of a variable combination of cervical dystonia with tremor, blepharospasm, oromandibular and laryngeal dystonia. Dystonia progresses slowly and might spread to become segmental. Arm tremor and myoclonic jerks in the arms or neck have also been reported. Caused by heterozygous mutation in the ANO3 gene on chromosome 11p14.	Preferred (foundation metadata concept)
A rare genetic isolated dystonia with characteristics of adult-onset non-progressive focal cervical dystonia typically manifesting with torticollis and occasionally accompanied by mild head tremor and essential-type limb tremor.	Preferred (foundation metadata concept)
A rare genetic isolated focal palmoplantar keratoderma disease with characteristics of focal thickening of the skin of the soles and often of the palms, associated with minimal or no nail involvement. Patients frequently present non-epidermolytic painful plantar blistering and occasionally subtle oral leukokeratosis or plantar hyperhidrosis. Caused by heterozygous mutation in the KRT6C gene on chromosome 12q13.	Preferred (foundation metadata concept)
A rare genetic isolated palmoplantar keratoderma disorder with characteristics of focal hyperkeratotic lesions affecting the pressure and mechanical trauma bearing areas of the palms and soles, as well as hyperkeratotic plaques involving joints, including knees, elbows, ankles and dorsa of interphalangeal joints. Caused by heterozygous mutation in the DSG1 gene on chromosome 18q12.	Preferred (foundation metadata concept)
A rare genetic isolated palmoplantar keratoderma disorder with characteristics of non-epidermolytic, diffuse hyperkeratotic lesions affecting both the palms and the soles, associated with a tendency of painful fissuring. Contrary to the clinical findings, histologic examination reveals findings suggestive of keratosis palmoplantaris striata, with ortho hyperkeratosis featuring widening of the intercellular spaces and dis-adhesion of keratocytes in the upper epidermal layers. Caused by heterozygous mutation in the DSG1 gene on chromosome 18q12.	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies syndrome with characteristics of hydranencephaly and diaphragmatic hernia along with macrocephaly, a widely open anterior fontanel, scaphoid abdomen and hypotonia. Additionally, congenital heart defects, polyhydramnios and pulmonary hypertension have also been associated.	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome characterized by consistently abnormal facial appearance, true or apparent hydrocephalus, motor and cognitive developmental delay, failure to thrive (feeding difficulties, vomiting, chest infections) and death within a few months of birth. Carp mouth, hairiness of the forehead, neonatal hyperbilirubinemia and advanced bone age may also be associated. There have been no further descriptions in the literature since 1991.	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome with characteristics of early intrauterine growth retardation, generalized edema, craniofacial dysmorphism (such as microcephaly, brachycephaly, frontal bossing, hypertelorism, short palpebral fissures, or absent nasal bone), cerebellar hypoplasia, sex reversal in male fetuses, congenital heart defects (including septal and valve defects and cardiomegaly) and late fetal loss.	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome with characteristics of facial dysmorphism (including long, downward slanting palpebral fissures, hypertelorism, posteriorly rotated ears, broad nasal bridge, short nose with a bulbous tip and anteverted nares, downturned corners of the mouth) as well as vertebral (occult spina bifida, hemivertebrae), brain (ventricular dilatation, agenesis of corpus callosum), cardiac (tetralogy of Fallot, ventricular septal defect) and gastrointestinal (short esophagus with intrathoracic stomach, small intestine, spleen and pancreas, anal atresia) malformations. There have been no further descriptions in the literature since 1991.	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome with characteristics of failure to thrive, severe developmental delay, severe postnatal microcephaly, frequent congenital cardiac defects and characteristic facial dysmorphism (including coarse face with anteverted nostrils, thin vermillion, prominent alveolar ridge and retro or micrognathia). Additional common features include neurologic abnormalities (hyper/hypotonia, sensorineural deafness, hydrocephalus, cerebral atrophy, seizures), as well as brachydactyly, cutis marmorata and genital anomalies. Caused by homozygous mutation in the FTO gene on chromosome 16q12.	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome with characteristics of mid-gestation lethality and features of a ciliopathy. Clinical manifestations include hydrocephalus, cerebellar vermis hypoplasia, corpus callosum agenesis, duodenal atresia, gastrointestinal malrotation, bilateral renal hypoplasia and dysmorphic craniofacial features (such as microcephaly, hypertelorism, low-set ears, prominent nose, short columella, cleft palate, micrognathia and wide mouth).	Preferred (foundation metadata concept)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome with characteristics of severe hydranencephaly and renal dysplasia or agenesis. Pregnancy is complicated by oligo or anhydramnios, leading to features of Potter sequence (including typical facies and microretrognathia, limb contractures, talipes equinovarus, and pulmonary hypoplasia) in the fetus. Affected fetuses either die in utero or shortly after birth. Histology of the brain shows widespread presence of multinucleated neurons and glial cells.	Preferred (foundation metadata concept)
A rare genetic lethal neurometabolic disease characterized by congenital cataracts, sensorineural hearing loss, severe psychomotor developmental delay, severe generalized muscular hypotonia and central nervous system abnormalities (including cerebellar and cerebral hypoplasia, hypomyelination, wide subarachnoid spaces) in the presence of low serum copper and ceruloplasmin. Nystagmus and seizures have also been reported. The disease is caused by homozygous or compound heterozygous mutation in the SLC33A1 gene on chromosome 3q25.	Preferred (foundation metadata concept)
A rare genetic lethal neurometabolic malformation syndrome with characteristics of multiple variable congenital cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with neonatal hypotonia, early-onset epileptic encephalopathy and myoclonic seizures. Craniofacial dysmorphism (prominent occiput, enlarged fontanelle, fused metopic suture, upslanted palpebral fissures, over folded helix, depressed nasal bridge, anteverted nose, malar flattening, Pierre-Robin sequence, high arched palate, short neck) and other manifestations (joint contractures, hyperreflexia, dysplastic nails, developmental delay) are also observed. Caused by mutation in the PIGA gene on chromosome Xp22.	Preferred (foundation metadata concept)
A rare genetic lethal non-dystrophic congenital myopathy disorder characterized, antenatally, by fetal akinesia, intrauterine growth restriction and polyhydramnios, and, following birth, by severe neonatal hypotonia, severe generalized skeletal, bulbar and respiratory muscle weakness, multiple flexion contractures, and normal creatine kinase serum levels. Ultrastructurally, loss of integrin alpha7, beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma and disruption of sarcomeres with disorganization of the Z band are observed. There is evidence this disease is caused by homozygous mutation in the CNTN1 gene on chromosome 12q12.	Preferred (foundation metadata concept)
A rare genetic lethal primary bone dysplasia with characteristics of dysmorphic craniofacial features (low-set, posteriorly rotated ears, hypertelorism, megalophthalmos, flattened and hypoplastic midface, micrognathia), hypomineralization of the calvarium, craniosynostosis, hypoplastic clavicles and pubis and bent long bones (particularly involving the femora). Caused by germline mutations in the FGFR2 gene. Prematurely erupted fetal teeth, osteopenia, hirsutism, clitoromegaly, gingival hyperplasia, and hepatosplenomegaly with extramedullary hematopoesis may also be associated.	Preferred (foundation metadata concept)
A rare genetic leukodystrophy characterized by developmental delay, increased muscle tone leading later to spasticity, mild ataxia, nystagmus, dysarthria, intentional tremor, and mild intellectual disability. Brain imaging reveals supratentorial and infratentorial hypomyelination.	Preferred (foundation metadata concept)
A rare genetic leukodystrophy disorder with characteristics of diffuse hypomyelination in the supratentorial brain white matter, brain stem and spinal cord. Patients usually present nystagmus, lower limb spasticity, hypotonia and motor developmental delay as well as MRI signal abnormalities involving the corpus callosum, anterior brainstem, pyramidal tracts, superior and inferior cerebellar peduncles, dorsal columns and/or lateral corticospinal tracts. Caused by homozygous or compound heterozygous mutation in the DARS gene on chromosome 2q21.	Preferred (foundation metadata concept)
A rare genetic leukodystrophy identified in families of Ashkenazi Jewish descent, characterized by infancy onset of severe global developmental delay with very limited or absent speech and sometimes complete absence of motor development, hypotonia, spasticity and acquired microcephaly. Seizures, hearing loss, visual impairment and autonomic dysfunction have also been described. Brain imaging shows delayed myelination and other white matter abnormalities.	Preferred (foundation metadata concept)
A rare genetic limb malformation syndrome with characteristics of multiple congenital distal joint contractures (including talipes equinovarus and both proximal and distal interphalangeal joint contractures of the hands) and very severe motor paralysis at birth (such as lack of swallowing, autonomous respiratory function and deep tendon reflexes), leading to death within first 3 months of life. Fetal hypo or akinesia, late-onset polyhydramnios and dramatically reduced, or absent, motor nerve conduction velocities are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons.	Preferred (foundation metadata concept)
A rare genetic limb reduction defects syndrome with characteristics of bilateral radial aplasia/hypoplasia manifesting with absent/short forearms in association with anogenital abnormalities (for example hypospadias or imperforate anus). Additional features reported include hydrocephalus and absent preaxial digits. There have been no further descriptions in the literature since 1993.	Preferred (foundation metadata concept)
A rare genetic lipodystrophy with characteristics of abnormal subcutaneous fat distribution, resulting in excess accumulation of fat in the face, neck, shoulders, axilla, trunk and pubic region, and loss of subcutaneous fat from the lower extremities. Variable common additional features are progressive adult onset myopathy, insulin resistance, diabetes, hypertriglyceridemia, hepatic steatosis, and vitiligo.	Preferred (foundation metadata concept)
A rare genetic lipodystrophy with characteristics of abnormal subcutaneous fat distribution, resulting in preservation of visceral, neck and axillary fat and absence of lower limb and gluteofemoral subcutaneous fat. Additional clinical features are acanthosis nigricans, insulin-resistant type II diabetes mellitus, dyslipidemia, and hypertension, leading to pancreatitis, hepatomegaly and hepatic steatosis.	Preferred (foundation metadata concept)
A rare genetic lipodystrophy with characteristics of loss of subcutaneous adipose tissue primarily affecting the lower limbs and gluteal region due to a defect in the PLIN1 gene. Associated features of insulin resistance, hepatic steatosis, dyslipidemia, hypertension, axillary acanthosis nigricans and muscular hypertrophy of the lower limbs are typical. Caused by heterozygous mutation in the PLIN1 gene on chromosome 15q26.	Preferred (foundation metadata concept)
A rare genetic lissencephaly with cerebellar hypoplasia subtype with characteristics of classical lissencephaly with thickened cortical gray matter (with either no discernable gradient, a predominantly posterior gradient, or a predominantly anterior gradient) associated with variable predominantly midline cerebellar hypoplasia.	Preferred (foundation metadata concept)
A rare genetic lissencephaly with cerebellar hypoplasia subtype with characteristics of the presence of lissencephaly with an abrupt transition, near the boundary between the frontal and parietal cortex, from frontal agyria to posterior gyral simplification, associated with cerebellar hypoplasia which predominantly affects the midline vermis.	Preferred (foundation metadata concept)
A rare genetic lymphoproliferative syndrome characterized by early onset recurrent infections, lymphadenopathy with hepatosplenomegaly and variable autoimmune disorders, including hemolytic anemia, thrombocytopenia, neutropenia, enteropathy, type I diabetes, scleroderma, arthritis, atopic dermatitis, and inflammatory lung disease. Patients commonly have failure to thrive. Variable immunologic findings include decreased regulatory T-cells, hypogammaglobulinemia, and reduction in memory B cells.	Preferred (foundation metadata concept)
A rare genetic macular dystrophy with characteristics of blurred vision, metamorphopsia and mild visual impairment secondary to a slightly elevated yellow egg yolk-like lesion located in the foveal or parafoveal region. Clinical onset is typically between the fourth and sixth decade of life. The mechanism underlying the physiopathology is unknown. An autosomal dominant inheritance with variable expression and incomplete penetrance is suggested but the disease can also be sporadic without evidence of a familial inheritance pattern.	Preferred (foundation metadata concept)
A rare genetic male infertility due to oligozoospermia (number of sperm in the ejaculate inferior to 15 million/mL) resulting from a mutation in a single gene known to cause oligozoospermia. Sperm morphology may be normal.	Preferred (foundation metadata concept)
A rare genetic male infertility due to sperm disorder with characteristics of the presence of spermatozoa with abnormal morphology, such as macrozoospermia or globozoospermia, in over 85% of sperm, resulting from mutation in a single gene known to cause teratozoospermia. It is a heterogeneous group that includes a wide range of abnormal sperm phenotypes affecting, solely or simultaneously, head, neck, midpiece and/or tail.	Preferred (foundation metadata concept)
A rare genetic male infertility with characteristics of azoospermia resulting from a mutation in a single gene known to cause azoospermia. Sperm morphology may be normal.	Preferred (foundation metadata concept)
A rare genetic malformation disorder with characteristics of cleft lip, with or without cleft palate, contractures of the lower extremities, abnormal external genitalia, syndactyly of fingers and/or toes, and a pyramidal skin fold over the hallux nail. Associated with mutations in the IRF6 gene (1q32.2-q32.3) which is involved in the formation of connective and epithelial tissues. Follows an autosomal dominant pattern of inheritance.	Preferred (foundation metadata concept)
A rare genetic malformation syndrome with characteristics of microcephaly, borderline intellectual disability, hyperpigmentation of the skin, short stature, and ventricular extrasystoles. Cardiac syncope may also be associated. There have been no further descriptions in the literature since 1975.	Preferred (foundation metadata concept)
A rare genetic malformation syndrome with short stature characterized by postnatal microcephaly, failure to thrive, global developmental delay and intellectual disability, hypotonia, dysmorphic features (short nose, depressed nasal bridge, low set ears, short neck, clinodactyly and cutaneous syndactyly of T2-3 at birth and broad forehead, midface retrusion, epicanthal folds, laterally sparse eyebrows, short nose, long philtrum, widely spaced teeth, micrognathia and coarsening of facial features later in life). Other associated features include postnatal transient generalized edema, myopia, strabismus, hypothyroidism.	Preferred (foundation metadata concept)
A rare genetic metabolic liver disease with characteristics of progressive neurodegeneration, cutaneous abnormalities including varying degrees of ichthyosis or seborrheic dermatitis, and systemic iron overload. Patients manifest with infantile-onset seizures, encephalopathy, abnormal eye movements, axial hypotonia with peripheral hypertonia, brisk reflexes, cortical blindness and deafness, myoclonus and hepato/splenomegaly, as well as oral manifestations including microdontia, widely spaced and pointed teeth with delayed eruption and gingival overgrowth.	Preferred (foundation metadata concept)
A rare genetic metabolite absorption and transport disorder characterized by progressive rod-cone dystrophy, usually presenting with impaired night vision in childhood, progressive loss of visual acuity and severe retinol deficiency without keratomalacia. Association with ocular colobomas, severe acne and hypercholesterolemia has been reported. There is evidence the disease can be caused by homozygous or compound heterozygous mutation in the RBP4 gene chromosome 10q23.	Preferred (foundation metadata concept)
A rare genetic mitochondrial DNA depletion syndrome characterized by neonatal or early-infantile onset hepatopathy (manifesting with hepatomegaly, cholestasis, increased transaminases, coagulopathy, hypoalbuminemia, ascites, and/or liver failure), associated with renal tubulopathy and progressive neurodegenerative manifestations, which include muscular atrophy, hyporeflexia, ataxia, sensory neuropathy, epilepsy, sensorineural hearing impairment, psychomotor regression, athetosis, nystagmus, and/or ophthalmoplegia. Patients typically present with recurrent vomiting, severe failure to thrive, feeding difficulties, and fasting hypoglycemia.	Preferred (foundation metadata concept)
A rare genetic mitochondrial DNA depletion syndrome with characteristics of severely reduced mitochondrial DNA content due to DGUOK deficiency typically manifesting with early-onset liver dysfunction, psychomotor delay, hypotonia, rotary nystagmus that develops into opsoclonus, lactic acidosis and hypoglycemia. Caused by homozygous or compound heterozygous mutation in the DGUOK gene on chromosome 2p13.	Preferred (foundation metadata concept)
A rare genetic mitochondrial DNA-related mitochondrial myopathy disorder with characteristics of slowly progressive muscular weakness (proximal greater than distal), predominantly involving the facial muscles and scapular girdle, associated with insulin-dependent diabetes mellitus. Neurological involvement and congenital myopathy may be variably observed. The phenotype is caused by mutation in the mitochondrially-encoded tRNA-glu gene (MTTE).	Preferred (foundation metadata concept)
A rare genetic mitochondrial disease with characteristics of early-onset progressive renal failure, manifesting with hyperuricemia, hyponatremia, hypomagnesemia, hypochloremic metabolic alkalosis, elevated BUN and polyuria, associated with systemic manifestations which include pulmonary hypertension, failure to thrive, global developmental delay, hypotonia and ventricular hypertrophy. Additional features include prematurity, elevated serum lactate, diabetes mellitus and in some pancytopenia. Caused by homozygous mutation in the SARS2 gene, which encodes mitochondrial seryl-tRNA synthetase on chromosome 19q13.2.	Preferred (foundation metadata concept)
A rare genetic mitochondrial disorder due to a defect in mitochondrial protein synthesis with characteristics of infantile-onset severe hypertrophic cardiomyopathy (that occasionally progresses to dilated cardiomyopathy) associated with failure to thrive, global development delay, muscular hypotonia, elevated serum lactate and complex I deficiency in skeletal muscle biopsy. Intellectual disability, pericardial effusion and a mild cardiac phenotype have been also reported. Caused by homozygous or compound heterozygous mutation in the ELAC2 gene on chromosome 17p12.	Preferred (foundation metadata concept)
A rare genetic mitochondrial myopathy disorder with characteristics of congenital cataract, progressive muscular hypotonia that particularly affects the lower limbs, reduced deep tendon reflexes, sensorineural hearing loss, global development delay and lactic acidosis. Muscle biopsy reveals reduced complex I, II and IV respiratory chain activity. Can be caused by mutations in the GFER gene.	Preferred (foundation metadata concept)
A rare genetic mitochondrial oxidative phosphorylation disorder that may present with a wide range of symptoms (including muscular hypotonia, hypertrophic cardiomyopathy, psychomotor delay, encephalopathy, peripheral neuropathy, lactic acidosis, 3-methylglutaconic aciduria) and clinical syndromes including Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome and Maternally inherited Leigh (MILS) syndrome.	Preferred (foundation metadata concept)
A rare genetic mitochondrial oxidative phosphorylation disorder with characteristics of a highly variable phenotype which ranges from a fatal neonatal/infantile encephalomyopathy with lactic acidosis, hyporeflexia/areflexia, severe hypotonia and respiratory failure to less severe cases presenting with central hypotonia, global developmental delay, congenital sensorineural hearing loss and renal disease. Additional variably observed clinical features include intellectual disability, seizures, and cardiomyopathy. Caused by homozygous or compound heterozygous mutation in the RMND1 gene on chromosome 6q25.	Preferred (foundation metadata concept)
A rare genetic mitochondrial oxidative phosphorylation disorder with characteristics of either late-onset myopathy with progressive external ophthalmoplegia and muscular weakness (predominantly limb-girdle) or early-onset myopathy presenting with decreased fetal movements, congenital ptosis, progressive external ophthalmoplegia, hypotonia and variably joint contractures. Reduced content and multiple deletions of mitochondrial DNA is observed in muscle biopsy. Caused by heterozygous mutation in the DNA2 gene on chromosome 10q.	Preferred (foundation metadata concept)
A rare genetic mitochondrial oxidative phosphorylation disorder with characteristics of infantile-onset encephalomyopathy presenting with developmental delay, slowly progressive hemiplegia, intractable epileptic seizures and asymmetrical brain atrophy with dilatation of the ipsilateral ventricle system. Additional features include optic atrophy, mildly increased plasma and/or CSF lactate and decreased cytochrome c oxidase activity in skeletal muscle biopsy.	Preferred (foundation metadata concept)
A rare genetic mitochondrial oxidative phosphorylation disorder with characteristics of intrauterine growth retardation, microcephaly, hypotonia, vision impairment, speech and language delay and lactic acidosis with reduced respiratory chain activity (typically complex I). Additional features may include macrocytic anemia, tremor, muscular atrophy, dysmetria and mild intellectual disability. Caused by homozygous or compound heterozygous mutation in the SFXN4 gene on chromosome 10q26.	Preferred (foundation metadata concept)
A rare genetic mitochondrial oxidative phosphorylation disorder with characteristics of potentially life-threatening severe myopathy manifesting in the neonatal to early infantile period, followed by marked spontaneous improvement of muscular function by early childhood. Associated biochemical findings include lactic acidosis and a transient marked decrease in respiratory chain activity.	Preferred (foundation metadata concept)
A rare genetic mixed autoinflammatory and autoimmune syndrome with characteristics of chronic systemic autoinflammation (presenting as recurrent fever in the neonatal or infantile period) and combined immunodeficiency (manifesting as recurrent viral and invasive bacterial infections). Muscular amylopectinosis may be subclinical or be complicated by myopathy/cardiomyopathy.	Preferred (foundation metadata concept)
A rare genetic motor neuron disease with characteristics of adult-onset of slowly progressive proximal muscular weakness with fasciculations, amyotrophy, cramps and absent/hypoactive reflexes without bulbar or pyramidal involvement. Caused by heterozygous mutation in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB) on chromosome 20q13.	Preferred (foundation metadata concept)
A rare genetic motor neuron disease with characteristics of decreased or absent fetal movements, congenital proximal and distal joint contractures (consistent with arthrogryposis multiplex congenita) and multiple congenital fractures of the long bones. Further manifestations are neonatal respiratory distress, severe muscular hypotonia, areflexia, dysphagia, congenital heart defects, and dysmorphic facial features. Muscle biopsy shows increased fiber-size variation and grouping of larger type I fibers. The disease is usually fatal in infancy due to respiratory failure.	Preferred (foundation metadata concept)
A rare genetic motor neuron disease with characteristics of late childhood or adolescent onset of slowly progressive severe distal limb muscle weakness and wasting, in association with pyramidal signs, normal sensation and absence of bulbar involvement. Leads to degeneration of motor neurons in the brain and spinal cord.	Preferred (foundation metadata concept)
A rare genetic motor neuron disease with characteristics of progressive early respiratory failure associated with diaphragm paralysis, distal muscular weakness, joint contractures, and axial hypotonia with preserved antigravity limb movements. The phenotype overlaps considerably with SMARD type 1 but is differentiated by a mutation in a different gene.	Preferred (foundation metadata concept)
A rare genetic motor neuron disease with characteristics of slowly progressive predominantly proximal muscular weakness and atrophy which typically manifests with muscle cramps, fasciculations, decreased/absent deep tendon reflexes, hand tremor and elevated serum creatine kinase at onset and later associates gait disturbances and impaired vibration sensation. There is evidence the disease is caused by heterozygous mutation in the CHCHD10 gene on chromosome 22q11.	Preferred (foundation metadata concept)
A rare genetic movement disorder with characteristics of autosomal dominant, adult-onset, slowly progressive, multifocal, cortical myoclonus. Patients present somatosensory-evoked, brief, jerky, involuntary movements in the face, arms and legs, associated in most of cases with sustained, multiple, sudden falls without loss of consciousness. Seizures or other neurological deficits, aside from mild cerebellar ataxia late in the course of the illness, are absent. The disease is caused by heterozygous mutation in the NOL3 gene on chromosome 16q22.	Preferred (foundation metadata concept)
A rare genetic movement disorder with characteristics of involuntary movements on one side of the body that mirror intentional movements on the opposite side of the body, which are present in various first-degree members of a family, persist beyond the first decade of life, and have no associated comorbidities.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies syndrome with characteristics of congenital heart defects (for example coarctation of the aorta with or without atrioventricular canal and subaortic stenosis), associated with tongue hamartomas, postaxial hand polydactyly and toe syndactyly. There is evidence the disease is caused by compound heterozygous mutation in the WDPCP gene on chromosome 2p15.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies syndrome with characteristics of second branchial arch anomalies (branchial cysts and fistulae), malformations of the outer, middle and inner ear associated with sensorineural, mixed or conductive hearing loss and the absence of renal abnormalities. Typical ear findings consist of malformed auricles (lop or cupped ears), preauricular pits and/or tags, and middle and/or inner ear dysplasias (including cochlear, vestibular and semicircular channel hypoplasia, malformation of the ossicles and of middle ear space).	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies syndrome with characteristics of short stature, hand brachydactyly with hypoplastic distal phalanges, global development delay, intellectual disability and more variably; seizures, obesity, and craniofacial dysmorphism that includes microcephaly, high forehead, flat face, hypertelorism, deep set eyes, flat nasal bridge, averted nostrils, long philtrum, thin lip vermilion and short neck. The malformation is due to a loss of function in the enzyme protein arginine N-methyltransferase 7 (encoded by PRMT7, 16q22.1) resulting in decreased levels of protein arginine methylation. Transmission is autosomal recessive.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic features-intellectual disability syndrome with characteristics of developmental and speech delay, intellectual disability, feeding difficulties, failure to thrive, growth retardation, and associated malformations such as abnormality of fingers and toes (i.e. clinodactyly of the fifth finger, second to third toe syndactyly), microcephaly, heart defects and upper airways anomalies. Observed facial dysmorphism includes hypertelorism, small, narrow or downslanting palpebral fissures, ptosis, epicanthus, ear malformations, broad nasal bridge, bulbous/prominent nose, short philtrum, thin lips, retrognathia/micrognathia, arched/cleft palate and dental anomalies. Additional variable manifestations include hearing and visual impairment, seizures, joint anomalies, obesity, and behavioral/psychiatric disorders.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by a variable phenotype including macrocephaly, postnatal overgrowth, advanced carpal ossification, obesity, speech delay, intellectual disability, autism spectrum disorders, and behavioral difficulties with aggressive outbursts, and variable facial dysmorphism. Seizures, structural abnormalities of the brain, as well as a variety of other manifestations such as recurrent otitis media, joint hypermobility, hirsutism, or nevi have also been reported.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by almost complete lack of B-cells and severe hypogammaglobulinemia, anomalies of the hands and feet, urogenital malformations and characteristic facial dysmorphism (including microcephaly, highly arched eyebrows, hypoplastic alae nasi and micrognathia). Most patients are developmentally normal although moderate intellectual disability has also been described.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by epiphyseal and vertebral dysplasia and abnormalities of the external ears (severe microtia or anotia) and the nose (hypoplastic nose with bifid tip, triangular nares or anteverted nares). Additional variable findings include short stature, localized aplasia cutis, hypodontia, synophrys, agenesis of the corpus callosum and cardiac, gastrointestinal and/or urogenital malformations among others. Psychomotor development may be delayed.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, variable degrees of intellectual disability and facial dysmorphism (including high nasal bridge, deep-set eyes, and wide mouth), often associated with feeding difficulties and/or gastroesophageal reflux. Additional reported manifestations are seizures, hypotonia, autistic features and joint laxity. Brain imaging may show non-specific features (such as cerebral atrophy).	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by growth retardation, short stature, developmental delay, intellectual disability, craniofacial dysmorphism (severe microcephaly, sloping forehead, prominent eyes, broad nasal ridge, hypoplastic nasal septum, epicanthal folds), spontaneous chromosomal instability, cellular hypersensitivity to ionizing radiation and radioresistant DNA synthesis, without severe infections, immunodeficiency or cancer predisposition. Additional reported features include mild spasticity, slight and nonprogressive ataxia, hyperopia, multiple pigmented nevi, widely spaced nipples, and clinodactyly.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by intellectual disability, obesity, macrocephaly, behavioral abnormalities (such as aggressive tantrums and autistic-like behavior), and delayed speech development. Dysmorphic facial features include large, square forehead, prominent supraorbital ridges, broad nasal tip, large ears, prominent lower lip, and minor dental anomalies such as small upper lateral incisors and central incisor gap.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable developmental delay and intellectual disability, movement disorder or gait abnormalities and dysmorphic craniofacial features (such as facial asymmetry, broad forehead, posteriorly rotated ears, thick lower lip, micrognathia, or cleft palate). A variety of congenital malformations have been reported in addition, including ocular, renal, cardiac and joint anomalies, among others. Some patients show behavioral alterations (autism, hyperactivity, or anxiety).	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable intellectual disability, developmental delay, autistic behavior, short stature and microcephaly. Additional variable manifestations include feeding problems, vision and hearing impairments, recurrent upper airway infections and epilepsy. Reported malformations are cryptorchidism and cerebral anomalies. Dysmorphic facial features include short and upslanted palpebral fissures, ptosis, telecanthus, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of agenesis of the corpus callosum, borderline or mild intellectual disability, macrocephaly and dysmorphic facial features (broad forehead, widely spaced eyes). Chiari type I malformation has also been reported in association.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of cerebellar-like ataxia, photosensitivity (mainly of the face and trunk), short stature and intellectual disability. Additional features include clinodactyly, single palmar transverse crease, high-arched palate, pseudohypertrophy of the calves and aortic valve lesions. There have been no further descriptions in the literature since 1983.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of choanal atresia, athelia or hypoplastic nipples, branchial arch abnormalities, external ear malformations, hearing loss, thyroid abnormalities, delayed or absent pubertal development and short stature. Developmental delay/intellectual disabilities are variably reported.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of congenital diaphragmatic hernia, short bowel, and asplenia. Dysmorphic facial features include long forehead, hypertelorism, upturned nares and small mandible. Atresia of the duodenum has also been reported.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of congenital microcephaly with facial dysmorphism (sloping forehead, prominent nose, mild retrognathia), moderate to severe, non-progressive intellectual disability and symmetrical digital malformations of variable degree, including brachydactyly of the fifth fingers with single flexion crease, clinodactyly, syndactyly, polydactyly and hallux valgus. Congenital anonychia and white cafe au lait-like spots on the skin of hands and feet are also associated. There is evidence this disease is caused by homozygous mutation in the RBBP8 gene on chromosome 18q11.2.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of congenital microcephaly, infantile-onset epileptic encephalopathy and profound developmental delay. Additional reported features include cortical visual impairment, sensorineural hearing loss, increased muscle tone, limb contractures, scoliosis and dysmorphic features like midface hypoplasia, narrow forehead, short nose, narrowed nasal bridge and small chin. Brain imaging may show thin corpus callosum and delayed myelination.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of congenital microcephaly, severe epilepsy with hypsarrhythmia, adducted thumbs, abnormal genitalia, and normal thyroid function. Hypotonia, moderate to severe psychomotor delay, and characteristic facial dysmorphism (including round face with prominent cheeks, blepharophimosis, large, bulbous nose with wide alae nasi, posteriorly rotated ears with dysplastic conchae, narrow mouth, cleft palate, and mild micrognathia) are additional characteristic features.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of craniofacial dysmorphism (including an abnormal skull shape, hypertelorism, downslanting palpebral fissures, epicanthal folds, low-set ears, depressed nasal bridge, micrognathia), short stature, ectodermal anomalies (such as sparse eyebrows, eyelashes, and scalp hair, hypoplastic toenails), developmental delay, and intellectual disability. Additional features may include cerebral/cerebellar malformations and mild renal involvement.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of craniofacial dysmorphism (midface hypoplasia, depressed nasal bridge, small nose with upturned tip, cleft palate, Pierre Robin sequence), bilateral, pronounced sensorineural hearing loss and skeletal/joint anomalies (including spondyloepiphyseal dysplasia, arthralgia/arthropathy), in the absence of ocular abnormalities. There is evidence the disease is caused by heterozygous mutation in the COL11A2 gene on chromosome 6p21.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of delayed motor development, intellectual disability, dysarthria, pseudobulbar signs, cryptorchidism, and syndactyly associated with a FLBN1 gene point mutation. Macular degeneration and signs of brain atrophy and spinal cord compression have also been reported.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay with intellectual disability, postnatal growth deficiency causing profound limb shortening with proximal and distal segments involvement, narrow chest, abnormalities of the spine, pelvis and metaphyses, corneal clouding and patent ductus arteriosus. Dysmorphic facial features include hypertelorism, prominent eyes, depressed nasal bridge and short upturned nose.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay with mild intellectual disability, short stature, facial dysmorphism (such as sparse hair, high forehead, deep-set eyes, short and upslanting palpebral fissures, short nose, anteverted nares, wide nasal base with broad nasal tip and broad columella, long philtrum, thin upper lip, and low-set, posteriorly rotated ears) and variable onset of sensorineural hearing loss and retinitis pigmentosa. Additional features are other ocular anomalies, abnormalities of the fingers, hypothyroidism, and signs of premature aging. Brain imaging shows cerebellar atrophy and dysmyelination.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay, intellectual disability and mild to moderate facial dysmorphism in association with variable brain malformations including abnormal gyration patterns, ventriculomegaly, white matter abnormalities, hypoplasia of the corpus callosum and cerebellar hemispheres. Musculoskeletal abnormalities include hemivertebrae, scoliosis or kyphosis, contractures, and joint laxity. Ocular involvement includes strabismus, hypermetropia and cortical visual impairment. Hypotonia may also be associated. Additional clinical manifestations may include seizures, short stature urogenital malformations, heart defects and gastrointestinal malformations. The disorder is due to a heterozygous de novo SON mutation (21q22.11), which encodes for a protein required for proper RNA splicing. Whilst the disease is autosomal dominant, all reported cases have occurred sporadically.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay, intellectual disability, thin habitus with narrow shoulders, mesomelic shortness of the arms, craniofacial dysmorphism (for example long lower face, maxillary hypoplasia, beak nose, short columella, prognathia, high arched palate, obtuse mandibular angle), brachydactyly (mostly involving middle phalanges) and cardiovascular anomalies (such as aortic root dilatation, mitral valve prolapse).	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay, moderate to severe intellectual disability, dysmorphic features including craniosynostosis, micro/retrognathia, cleft palate, brachydactyly and short stature. Seizures, skeletal anomalies (such as arthrogryposis, gracile bones and pathological fractures) and renal abnormalities have also been described. Cerebral MRI may show periventricular white matter changes and ventriculomegaly.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of dysmorphic facial features including high forehead, elongated and flattened midface, arched and sparse eyebrows, short palpebral fissures, telecanthus, long nose with hypoplastic nostrils, long philtrum, high and narrow palate and microstomia with downturned corners. Ears are characteristically malformed, large, low-set and posteriorly rotated and nasal speech is associated.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of early macrosomia, bilateral severe microphthalmia and a protuberant abdomen with hepatomegaly. Additional reported features include brachycephaly, large fontanelles, prominent forehead, upturned nose and median cleft palate. Cyanotic apneic spells and overwhelming infection lead to death within the first 6 months of life. There have been no further descriptions in the literature since 1989.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of facial dysmorphism (mild eyelid ptosis, xanthelasma, anteverted nostrils, bifid nasal tip, short palate), severe muscle wasting and cachexia, retinitis pigmentosa, numerous lentigines and cafe-au-lait spots, as well as mild soft tissue syndactyly. Additional features include nasal speech, chest asymmetry, pectus excavatum, genu varum, pes planus, and thyroid papillary carcinoma and diffuse enlargement. There has been no further description in the literature since 1984.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay and intellectual disability, infantile hypotonia, microcephaly, movement disorder and impaired balance. Variable manifestations include hearing loss, cortical visual impairment, abnormalities of fingers and/or toes, congenital cardiac anomalies, kyphoscoliosis, dysmorphic facial features, abnormal sleep pattern and seizures.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay and intellectual disability, progressive spondyloepimetaphyseal dysplasia, short stature, short fourth metatarsals and dysmorphic craniofacial features (including microcephaly, hypertelorism, epicanthal folds, mild ptosis, strabismus, malar hypoplasia, short nose, depressed nasal bridge, full lips, small, low-set ears and short neck). Craniosynostosis, generalized hypotonia, as well as asymmetry of the cerebral hemispheres and mild thinning of the corpus callosum on brain imaging have also been described.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay and moderate to severe intellectual disability, as well as variable other manifestations, such as macro- or microcephaly, epilepsy, hypotonia, stereotypic movements and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, upturned nose, dysplastic ears, and broad mouth). Brain imaging may show cerebellar anomalies, hypoplastic corpus callosum, enlarged ventricles, polymicrogyria or white matter abnormalities.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, axial hypotonia, palate abnormalities (including cleft palate and/or high and narrow palate), dysmorphic facial features (including prominent forehead, hypertelorism, downslanting palpebral fissures, wide nasal bridge, thin lips and widely spaced teeth) and short stature. Additional manifestations may include digital anomalies (such as brachydactyly, clinodactyly and hypoplastic toenails) a single palmar crease, lower limb hypertonia, joint hypermobility along with ocular and urogenital anomalies.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, intellectual disability and dysmorphic facial features including facial asymmetry, prominent forehead, short palpebral fissures, low nasal bridge, smooth and long philtrum, thin upper lip, low-set posteriorly rotated dysplastic ears exclusively affecting females. Additional reported manifestations include short stature, choanal atresia, scoliosis, congenital ocular, dental, cardiac and urogenital anomalies, along with hypotonia, seizures and structural brain abnormalities.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, intellectual disability, absent scrotum or labia majora, absent or underdeveloped nipples and a tuft of hair extruding from the lactiferous ducts, bilateral corneal opacities, and dysmorphic craniofacial features (microcephaly, short forehead, and ear abnormalities, among others). Patients also show horizontal nystagmus and ataxic gait. Brain MRI reveals small cerebellar hemispheres and vermis and a small pons.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, intellectual disability, growth retardation, hypotonia, cerebellar symptoms such as ataxia, spondyloepiphyseal dysplasia and dysmorphic craniofacial features (including microcephaly, dolichocephaly, prominent ears, epicanthus, broad nasal bridge, long and flat philtrum, or small mouth). Additional reported manifestations are epilepsy, retinitis pigmentosa and urogenital abnormalities among others. Brain imaging may show cerebellar hypoplasia.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, intellectual disability, hypotonia, craniofacial dysmorphism (such as ridged metopic sutures, long palpebral fissures, broad nasal bridge, hypoplastic alae nasi, low-set, prominent ears, prominent midline tongue groove and downturned mouth), congenital heart defects and variable skeletal abnormalities including hip dysplasia, vertebral anomalies and scoliosis. Additional reported manifestations include high pain tolerance and genitourinary anomalies. Brain imaging may show a thin corpus callosum or white matter abnormalities.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, intellectual disability, hypotonia, seizures and autism spectrum disorder. Variable associated features include ophthalmologic anomalies, congenital heart defects, genitourinary defects and craniofacial dysmorphism (including frontal bossing, epicanthal folds, low-set, posteriorly rotated ears, anteverted nares and micrognathia). Brain imaging may show thinning of the corpus callosum, white matter abnormalities, ventriculomegaly and a small cerebellar vermis.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay, intellectual disability, seizures, abnormal gait and craniofacial dysmorphism (including coarse features, depressed nasal bridge, anteverted nares, broad nasal tip, prominent maxilla and upper lip, wide mouth, abnormal gingiva and widely spaced teeth). Additional reported manifestations are ocular anomalies, cardiac defects, gastrointestinal problems and autistic features. Brain imaging may show thin corpus callosum, white matter abnormalities, or dilated ventricles.	Preferred (foundation metadata concept)
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of intellectual disability, developmental delay, delayed bone age, short stature, generalized muscle weakness and dysmorphic facial features (such as high arched eyebrows, downslanting palpebral fissures, prominent nose and narrow palate and mouth). Additional reported manifestations include blue sclerae, ophthalmoplegia and intention tremor. Brain imaging may show white matter abnormalities.	Preferred (foundation metadata concept)

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Reference Sets

Reference set descriptor

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Id	Description	Lang	Type	Status	Case?	Module
900000000001115012	United States of America English language reference set	en	Synonym (core metadata concept)	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)
900000000001116013	US English	en	Synonym (core metadata concept)	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)
900000000001117016	United States of America English language reference set (foundation metadata concept)	en	Fully specified name	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)