900000000000508004: Great Britain 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)\GB 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
GB 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 ectodermal dysplasia syndrome with characteristics of sparse to absent scalp hair, eyebrows, and eyelashes (with pili torti when present), widely spaced, conical-shaped teeth with peg-shaped, conical crowns and enamel hypoplasia and palmoplantar hyperkeratosis, associated with partial cutaneous syndactyly in hands and feet. Caused by homozygous or compound heterozygous mutation in the PVRL4 gene (NECTIN4) on chromosome 1q23.	Preferred (foundation metadata concept)
A rare genetic ectodermal dysplasia syndrome with characteristics of sparse, thin brittle scalp hair as well as sparse eyebrows, eyelashes, axillary and pubic hair, delayed eruption of deciduous teeth and hypodontia of both dentitions. Mild palmoplantar keratosis, cafe au lait spots on back, mild dystrophy of nails and tibial deflection of toes are also associated. There have been no further descriptions in the literature since 1986.	Preferred (foundation metadata concept)
A rare genetic endocrine disease characterised by neonatal macrosomia, asymmetrical overgrowth (typically manifesting as left-sided hemihypertrophy) and recurrent, severe hypoinsulinaemic (or hypo ketotic hypo-fatty-acidaemic) hypoglycaemia in infancy, which results in episodes of reduced consciousness and seizures. There is evidence the disease can be caused by heterozygous mutation in the AKT2 gene on chromosome 19q13.	Preferred (foundation metadata concept)
A rare genetic endocrine disease characterised by the association of common variable immunodeficiency manifesting with hypogammaglobulinaemia and recurrent or severe childhood-onset sinopulmonary infections, followed, possibly many years later, by symptomatic adrenocorticotropic hormone (ACTH) deficiency resulting from anterior pituitary hormone deficiency. Caused by heterozygous mutation in the NFKB2 gene on chromosome 10q24.	Preferred (foundation metadata concept)
A rare genetic endocrine disease with characteristics of a defect in conversion of cortisone to active cortisol, resulting in ACTH-mediated excessive androgen release from adrenal glands. Premature adrenarche is typical with precocious pseudopuberty, proportionate tall stature and accelerated bone maturation in males and hirsutism, oligoamenorrhoea, central obesity and infertility in females. Imaging studies may indicate adrenal hyperplasia.	Preferred (foundation metadata concept)
A rare genetic endocrine disease with characteristics of central hypothyroidism, testis enlargement in adolescence resulting in adult macroorchidism, delayed pubertal testosterone rise with a subsequent delayed pubertal growth spurt, small thyroid gland, and variable prolactin and growth hormone deficiency. Caused by mutation in the IGSF1 gene on chromosome Xq26.	Preferred (foundation metadata concept)
A rare genetic endocrine disease with characteristics of early-onset (before the age of five years old) excessive acceleration of linear growth and body size due to pituitary mixed growth hormone and prolactin secreting adenomas and/or mixed-cell pituitary hyperplasia. Patients present gigantism and may associate acromegalic features (for example coarse facial features, frontal bossing, prognathism, increased interdental space) as well as marked enlargement of hands and feet, soft tissue swelling, appetite increase and acanthosis nigricans.	Preferred (foundation metadata concept)
A rare genetic endocrine disease with characteristics of idiopathic short stature due to diminished GHR function (decreased ligand binding or reduced availability of receptor), thus resulting in partial insensitivity to growth hormone. There is evidence the disease is caused by heterozygous mutation in the growth hormone receptor gene (GHR) on chromosome 5p13-p12.	Preferred (foundation metadata concept)
A rare genetic endocrine disorder characterised by persistently high prolactin serum levels (not associated with gestation, puerperium, drug intake or pituitary tumour) in multiple affected family members. Clinically it manifests with signs usually observed in hyperprolactinaemia, which are: secondary medroxyprogesterone acetate (MPA)-negative amenorrhoea and galactorrhoea in female patients, and hypogonadism and decreased testosterone level-driven sexual disfunction in male patients. Oligomenorrhoea and primary infertility have also been reported in some female patients.	Preferred (foundation metadata concept)
A rare genetic endocrine growth disease resulting from growth hormone secretagogue receptor (GHSR) deficiency. The disease has characteristics of postnatal growth delay that results in short stature. The pituitary gland is typically without morphological changes, although anterior pituitary gland hypoplasia has been reported.	Preferred (foundation metadata concept)
A rare genetic epidermal disease with characteristics of early childhood-onset of punctate palmoplantar keratoderma in association with adult-onset leucoencephalopathy manifested by progressive tetrapyramidal syndrome and cognitive deterioration.	Preferred (foundation metadata concept)
A rare genetic epidermal disorder with characteristics of a chronic diffuse fine scaly erythematous rash on the face (predominantly the chin, nasolabial folds, eyebrows) around the earlobes and over the scalp, associated with hyperkeratosis over elbows, knees, palms, soles and metacarpophalangeal joints, in the absence of associated rheumatological or neurological disorders. Cold weather, emotional stress and strenuous physical activity may exacerbate symptoms. There is evidence the disease is caused by mutation in the ZNF750 gene.	Preferred (foundation metadata concept)
A rare genetic epidermal disorder with characteristics of congenital erythroderma with severe psoriasiform dermatitis, ichthyosis, severe palmoplantar keratoderma, yellow keratosis on the hands and feet, elevated immunoglobulin E, multiple food allergies, and metabolic wasting. Other variable features may include hypotrichosis, nail dystrophy, recurrent infections, mild global developmental delay, eosinophilia, nystagmus, growth impairment and cardiac defects.	Preferred (foundation metadata concept)
A rare genetic epilepsy characterised by relatively large head circumference or macrocephaly, diminished or absent deep-tendon reflexes and mild gross motor delay in infancy, followed by intractable focal seizures with language regression, behavioural abnormalities (hyperactivity, attention deficit, aggressive/autoaggressive behaviour, autistic features) and intellectual disability later in life.	Preferred (foundation metadata concept)
A rare genetic epilepsy disorder with characteristics of autosomal dominant lesional and nonlesional focal epilepsy with variable penetrance. Focal seizures emanate from different cortical locations (temporal, frontal, centroparietal, parietal, parietal-occipital, occipital) in different family members, but for each individual a single focus remains constant throughout lifetime. Seizure type (tonic, tonic-clonic or hyperkinetic) and severity varies among family members and tends to decrease (but do not disappear) during adulthood. Many patients have an aura and show automatisms during diurnal seizures whereas others have nocturnal seizures. Most individuals are of normal intelligence but patients with intellectual disability, autistic spectrum disorder and obsessive-compulsive disorder have been described.	Preferred (foundation metadata concept)
A rare genetic epilepsy syndrome characterised by neonatal or early infantile onset of severe, progressive, typically frequent and prolonged myoclonic seizures that are refractory to treatment, associated with localised and/or generalised paroxysmal dystonia (which later becomes persistent). Other features include severe hypotonia, hemiplegia, psychomotor regression (or lack of psychomotor development) and progressive cerebral and cerebellar atrophy, with affected individuals becoming progressively non-reactive to environmental stimuli.	Preferred (foundation metadata concept)
A rare genetic epilepsy syndrome with characteristics of congenital alopecia, early-onset epilepsy, intellectual disability and speech delay. Large stature, delayed bone development and abnormal electroencephalogram have also been associated.	Preferred (foundation metadata concept)
A rare genetic erythrokeratoderma disorder characterised by generalised cutaneous erythema with fine white scales and pruritus refractory to treatment, progressive dilated cardiomyopathy, palmoplantar keratoderma, sparse or absent eyebrows and eyelashes, sparse scalp hair, nail dystrophy and dental enamel anomalies. Variable features include failure to thrive, developmental delay and development of corneal opacities. Histology shows psoriasiform acanthosis, hypogranulosis, and compact orthohyperkeratosis.	Preferred (foundation metadata concept)
A rare genetic eye disease with characteristics of foveal hypoplasia, optic nerve misrouting with an increased number of axons decussating at the optic chiasm and innervating the contralateral cortex, and posterior embryotoxon or Axenfeld anomaly (indicating anterior segment dysgenesis), in the absence of albinism. Patients present congenital nystagmus, decreased visual acuity, refractive errors and occasionally strabismus. Microphthalmia and retinochoroidal coloboma may also be associated. There is the disease is caused by homozygous or compound heterozygous mutation in the SLC38A8 gene on chromosome 16q23.	Preferred (foundation metadata concept)
A rare genetic eye disease with characteristics of microcornea, coloboma of the iris and the optic disc, axial enlargement of the globe, staphyloma and severe myopia. Additional manifestations are mild cornea plana, iridocorneal angle abnormalities with elevation of intraocular pressure and shallow anterior chamber depth. Variable expressivity of the phenotype has been described, including unilateral or bilateral involvement or variable extent of coloboma among other features.	Preferred (foundation metadata concept)
A rare genetic familial partial epilepsy disease with characteristics of focal seizures associated with prominent ictal auditory symptoms, and/or receptive aphasia, presenting in two or more family members and having a relatively benign evolution.	Preferred (foundation metadata concept)
A rare genetic familial partial epilepsy disease with characteristics of simple partial seizures, complex partial seizures and/or secondarily generalised seizures, originating from the inner aspect of the temporal lobe, associated with an antecedent history of febrile seizures, occurring in various members of a family. Hippocampal abnormalities (for example hippocampal sclerosis) may also be associated. There is evidence the disease is caused by homozygous mutation in the CPA6 gene on chromosome 8q13.	Preferred (foundation metadata concept)
A rare genetic female infertility disorder with characteristics of the presence of abnormal oocytes that lack a zona pellucida. Affected individuals are unable to conceive despite having normal menstrual cycles and sex hormone levels, as well as no obstruction in the fallopian tubes or defects of the uterus or adnexa.	Preferred (foundation metadata concept)
A rare genetic female infertility with characteristics of oocyte maturation arrest during any of the various stages of meiosis I or II. In some patients, first polar body oocytes may be retrieved, but these either shows fertilisation failure or early embryonic arrest. Affected women have regular menstrual cycles.	Preferred (foundation metadata concept)
A rare genetic form of obesity characterised by morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidaemia leading to early coronary disease, myocardial infarction and congestive heart failure. Intellectual disability and decreased sperm counts or azoospermia have also been reported.	Preferred (foundation metadata concept)
A rare genetic form of obesity characterised by severe early-onset obesity, hyperphagia, insulin resistance with hyperinsulinaemia, reduced adult final height, delayed speech and language development and a tendency for social isolation and aggressive behaviour.	Preferred (foundation metadata concept)
A rare genetic form of obesity with characteristics of severe early-onset obesity, hyperphagia and variable presence of cognitive impairment and behavioural disorder, including autistic spectrum behaviour, impaired concentration and memory deficit. Some patients present with Prader-Willi-like features such as hypotonia, developmental delay, intellectual disability, short stature, hypopituitarism and dysmorphic facial features.	Preferred (foundation metadata concept)
A rare genetic form of primary immunodeficiency characterised by life-threatening bacterial, fungal and viral infections with the onset in infancy and failure to thrive. Typically, hypogammaglobulinaemia or agammaglobulinaemia and normal levels of T and B cells are present. There is evidence the disease is caused by homozygous mutation in the IKBKB gene on chromosome 8p11.	Preferred (foundation metadata concept)
A rare genetic form of primary immunodeficiency with characteristics of growth retardation, early recurrent pulmonary infections leading to bronchiectasis, inflammatory gastrointestinal disease, and other symptoms, such as rash, dermatitis, skin infections. Caused by homozygous mutation in the MALT1 gene on chromosome 18q21.	Preferred (foundation metadata concept)
A rare genetic gastroenterological disease characterised by the early onset of chronic diarrhoea, vomiting, anorexia, lactic acidosis, renal insufficiency and hepatic involvement (mild elevation of liver enzymes, steatosis, hepatomegaly). Partial villous atrophy (with eosinophilic infiltration) is observed on intestinal biopsy. Although diarrhoea may resolve, the development of neurologic symptoms (cerebellar ataxia, sensorineural deafness, seizures), retinitis pigmentosa and muscle weakness may complicate disease course and lead to death. There have been no further descriptions in the literature since 1994.	Preferred (foundation metadata concept)
A rare genetic gastroenterological disease characterised by the presence of multiple persistent, intractable ulcers of the small intestine, leading to chronic blood and protein loss. Signs and symptoms include abdominal pain, anaemia, fatigue, oedema, and diarrhoea. Morphologically, the condition manifests with multiple sharply demarcated shallow lesions with irregular circular or linear shape.	Preferred (foundation metadata concept)
A rare genetic glycogen storage disorder with characteristics of polyglucosan accumulation in various tissues, manifesting with progressive proximal muscle weakness in the lower limbs and rapidly progressive usually dilated cardiomyopathy. Hepatic involvement and growth retardation may be associated. Early-onset immunodeficiency and auto-inflammation presenting with recurrent bacterial infections have also been reported. Caused by homozygous or compound heterozygous mutation in the RBCK1 gene on chromosome 20p13.	Preferred (foundation metadata concept)
A rare genetic haematologic and intestinal disease characterised by childhood onset of bleeding tendency with epistaxis, gum bleeding, gastrointestinal bleeding, haematuria and menorrhagia due to impaired platelet aggregation and secretion, as well as recurrent gastrointestinal ulcer. Mildly reduced levels of coagulation factor XI have been reported in addition.	Preferred (foundation metadata concept)
A rare genetic haematologic and neurologic disease characterised by chronic Coombs-negative haemolysis. The disease is associated with early-onset relapsing immune-mediated inflammatory axonal or demyelinating sensory-motor peripheral polyneuropathy and isolated or recurrent cerebrovascular events (in anterior or posterior circulation).	Preferred (foundation metadata concept)
A rare genetic haematologic disease characterised by increased levels of serum haemoglobin, haematocrit and erythrocyte mass, associated with elevated or inappropriately normal erythropoietin serum levels, occurring in various members of a family and with autosomal dominant inheritance.	Preferred (foundation metadata concept)
A rare genetic haematologic disorder characterised by bone marrow failure which manifests with aplastic anaemia and/or myelodysplasia, associated with hearing/ear abnormalities (such as deafness, labyrinthitis), inherited in an autosomal dominant manner. Caused by heterozygous mutation in the SRP72 gene on chromosome 4q12.	Preferred (foundation metadata concept)
A rare genetic haematologic disorder characterised by progressive trilineage bone marrow failure (with hypocellularity), developmental delay with learning disabilities and microcephaly. Mild facial dysmorphism and hypotonia have also been reported. There is evidence the disease is caused by homozygous mutation in the ERCC6L2 gene on chromosome 9q22.	Preferred (foundation metadata concept)
A rare genetic haemoglobinopathy characterised by generally mild clinical phenotype, high fetal haemoglobin levels and mild microcytosis and hypochromia. In some cases, acute sickle cell disease manifestations were reported, namely acute chest syndrome and acute pain crisis.	Preferred (foundation metadata concept)
A rare genetic haemoglobinopathy disorder due to a defect in the gama subunit of the fetal haemoglobin and characterised by neonatal cyanosis, low haemoglobin oxygen saturation levels without arterial hypoxaemia, moderate anaemia and reticulocytosis, not associated with heart or lung disease. Symptoms progressively subside within the first months of life. Can be caused by heterozygous mutation in the HBG2 gene on chromosome 11p15.5.	Preferred (foundation metadata concept)
A rare genetic hair anomaly with characteristics of a prolonged anagen phase of the eyelash hairs, leading to extreme eyelash growth that may result in corneal irritation. Increased growth of hair on other parts of the face (eyebrows, cheeks, forehead) and/or the body (chest, arms, legs) may be associated. There is evidence the disease is caused by homozygous mutation in the FGF5 gene on chromosome 4q21.	Preferred (foundation metadata concept)
A rare genetic heart-hand syndrome with characteristics of typical manifestations of the Carney complex (spotty pigmentation of the skin, familial cardiac and cutaneous myxomas and endocrinopathy) associated with trismus and distal arthrogryposis (presenting as involuntary contraction of distal and proximal interphalangeal joints of hands evident only on dorsiflexion of wrist and similar lower-limb contractures producing foot deformities).	Preferred (foundation metadata concept)
A rare genetic hepatic disease characterised by massive hepatomegaly, moderate to severe transient hypertriglyceridaemia and hepatic steatosis (followed by fibrosis) manifesting in infancy with failure to thrive, vomiting, an enlarged abdomen and a fatty liver. Reduction or normalisation of triglyceride serum levels occurs with advancing age. Caused by homozygous or compound heterozygous mutation in the GPD1 gene on chromosome 12q13.	Preferred (foundation metadata concept)
A rare genetic hepatic disease characterised by the presence of green colouration of the skin, urine, plasma and other body fluids (ascites, breastmilk) or parts (sclerae) due to increased serum levels of biliverdin in association with biliary obstruction and/or liver failure. Association with malnutrition, medication, and congenital biliary atresia has also been reported. Can be caused by heterozygous or homozygous mutation in the gene encoding bilirubin reductase-alpha (BLVRA) on chromosome 7p13.	Preferred (foundation metadata concept)
A rare genetic hereditary poikiloderma syndrome characterised by early-onset poikiloderma (mainly on the face), hypotrichosis, hypohidrosis, muscle and tendon contractures with varus foot deformity, progressive proximal and distal muscle weakness in all extremities and progressive pulmonary fibrosis. Mild lymphoedema of the extremities, growth retardation, liver impairment, exocrine pancreatic insufficiency and haematologic abnormalities are additional variable features. There is evidence the disease is caused by heterozygous mutation in the FAM111B gene on chromosome 11q12.	Preferred (foundation metadata concept)
A rare genetic human prion disease characterised by adult-onset neurodegenerative manifestations associated with a movement disorder and psychiatric/behavioural disturbances. Patients typically present personality changes, aggressiveness, manias, anxiety and/or depression in conjunction with rapidly progressive cognitive decline (presenting with dysarthria, apraxia, aphasia and eventually leading to dementia) as well as ataxia (manifesting with gait disturbances, unsteadiness, coordination problems), Parkinsonism, myoclonus, and/or chorea. Additional features may include generalised spasticity, seizures, urine incontinence and pyramidal abnormalities. There is evidence the disease is caused by 8 extra octapeptide repeats in the PRNP gene on chromosome 20p13.	Preferred (foundation metadata concept)
A rare genetic hyperkinetic movement disorder with predominant characteristics of chorea of variable severity associated with bilateral striatal abnormalities on cerebral MRI. The disease is not progressive and cognitive performance is preserved in the majority of cases, although mild cognitive delay has also been reported.	Preferred (foundation metadata concept)
A rare genetic hypertension with characteristics of a familial severe hypertension with an onset before age 20 years, associated with suppressed plasma renin and low aldosterone levels in the presence of low or normal levels of the mineralocorticoid aldosterone, that is highly resistant to antihypertensive medication. During pregnancy, there is a marked exacerbation of hypertension, accompanied by low serum potassium levels and undetectable aldosterone levels, but without signs of preeclampsia, requiring early delivery.	Preferred (foundation metadata concept)
A rare genetic immune disease characterised by early onset of recurrent bacterial, viral and fungal infections, chronic inflammatory bowel disease, gastritis and inflammatory polyarthritis. Patients present with diarrhoea, vomiting, hepatosplenomegaly, mouth ulcers, perianal abscesses, chronic lung disease with bronchiectasis and failure to thrive. Occurrence of a skin rash associated with lymphocytic vasculitis has also been reported. Immunologic abnormalities include variable T-cell lymphopenia, decreased natural killer cells, and decreased B-cells with variable hypogammaglobulinaemia.	Preferred (foundation metadata concept)
A rare genetic immune disease characterised by recurrent sinopulmonary infections and autoimmune enterocolopathy, manifesting as frequent episodes of intractable diarrhoea with abdominal pain and fever, accompanied by eczematous rashes, due to deficits in components of innate and adaptive immunity. Immunologic abnormalities include IgG subclass deficiency, impaired antigen-induced lymphocyte proliferation, reduced cytokine production by CD8+ T lymphocytes and decreased numbers of natural killer cells.	Preferred (foundation metadata concept)
A rare genetic immuno-osseous dysplasia disorder with characteristics of pre and post-natal growth retardation, hypotonia, borderline to moderate intellectual disability, retinal dystrophy, spondyloepiphyseal dysplasia (epiphyseal dysplasia, epiphyses ossification delay, vertebral changes) and skeletal anomalies (brachydactyly, fifth finger clinodactyly). Also associated are humeral immunodeficiency with inability to generate specific antibodies and low circulating B-cells, craniofacial dysmorphism that typically includes microcephaly, hypertelorism, long palpebral fissures, prominent eyelashes, a narrow, tubular, upturned nose with hypoplastic alae nasi, long philtrum and thin upper lip. There is evidence the disease is caused by compound heterozygous mutation in the RNU4ATAC gene on chromosome 2q14.	Preferred (foundation metadata concept)
A rare genetic immunodeficiency due to a complement cascade protein anomaly characterised by low or undetectable serum ficolin 3 levels, susceptibility to infections and possibly autoimmunity. The presentation is variable, from perinatal necrotising enterocolitis and recurrent skin infections with Staphylococcus aureus to childhood-onset recurrent pulmonary infections leading to brain abscesses and pulmonary fibrosis, to membranous nephropathy. In some patients clinical consequences of ficolin 3 deficiency were not clear. There is evidence that ficolin 3 deficiency is caused by homozygous mutation in the FCN3 gene on chromosome 1p36.	Preferred (foundation metadata concept)
A rare genetic immunodeficiency due to a complement cascade protein anomaly with characteristics of low serum levels of MASP-2 and a variable susceptibility to bacterial infections (for example pulmonary tuberculosis, pneumococcal pneumonia, skin abscesses and sepsis), and autoimmune diseases (for example inflammatory lung disease, cystic fibrosis, systemic lupus erythematosus). In many cases it remains asymptomatic. There is evidence the disease is caused by homozygous mutation in the MASP2 gene on chromosome 1p36.	Preferred (foundation metadata concept)
A rare genetic immunological disease reported in a single consanguineous Pakistani family with several affected members presenting with severe bacterial and viral infections, recurrent hepatopathy (portal inflammation, fibrosis) and recurrent, stereotypical febrile episodes, sometimes lasting several days, with encephalopathy and difficult-to-control seizures. Variable cardiac malformations were also reported. Although there were autoimmune lymphoproliferative syndrome (ALPS)-like biological features, clinical ALPS was not present. A homozygous missense mutation in the FADD gene (11q13.3) was found in the family and the disease is thought to follow an autosomal recessive pattern of inheritance.	Preferred (foundation metadata concept)
A rare genetic inborn error of branched-chain amino acid metabolism disorder, with a highly variable clinical and biochemical phenotype. Typical characteristics are mild to severe global developmental delay, elevated methylmalonic acid and occasionally lactic acid plasma levels and chronic methylmalonic aciduria, which may be accompanied by elevation of additional organic or amino acids in urine (for example beta-alanine, methionine, 3-hydroxypropionic, 3-aminoisobutyric and/or 3-hydroxyisobutyric acid). Microcephaly, mild craniofacial dysmorphism, axial hypotonia, liver failure and central nervous system abnormalities on MRI have also been reported. Caused by homozygous or compound heterozygous mutation in the ALDH6A1 gene on chromosome 14q24.	Preferred (foundation metadata concept)
A rare genetic inborn error of metabolism characterised by a relatively benign clinical phenotype, with only mild to moderate hepatomegaly reported, in addition to laboratory studies revealing permanent, greatly increased hypermethioninaemia, mild to moderate elevation of aminotransferases and highly elevated plasma S-adenosyl-methionine with normal S-adenosylhomocysteine and total homocysteine. The disease is caused by homozygous or compound heterozygous mutation in the GNMT gene on chromosome 6p21.	Preferred (foundation metadata concept)
A rare genetic infantile epilepsy syndrome disease with characteristics of neonatal to infancy onset myoclonic focal seizures occurring in various members of a family, associated in some with mild dysarthria, ataxia and borderline-to-moderate intellectual disability.	Preferred (foundation metadata concept)
A rare genetic intellectual disability characterised by the association of intellectual disability with variable other anomalies in the absence of a well-characterised syndrome. Associated abnormalities may include facial dysmorphism, neurological signs and symptoms, behavioural problems, and abnormalities of various other organ systems.	Preferred (foundation metadata concept)
A rare genetic intellectual disability syndrome with characteristics of delayed motor and cognitive development, absence or severe delay in speech development, intellectual disability and alacrima. Achalasia/dysphagia and mild autonomic dysfunction (anisocoria) have also been reported in some patients. The phenotype is similar to the one observed in autosomal recessive Triple A syndrome, but differs by the presence of intellectual disability in all affected individuals.	Preferred (foundation metadata concept)
A rare genetic intellectual disability syndrome with characteristics of macrocephaly, hypotonia, dysmorphic facial features (wide forehead, ptosis, downslanting palpebral fissures, enlarged and calcified external ears, large jaw), sparse body hair and tall stature. Hearing loss, insulin-resistant diabetes, and progressive distal muscle wasting (leading to joint contractures) have also been reported in adulthood. Rare manifestations include hypothyroidism, cerebral calcification, ataxia and peripheral neuropathy. There is evidence this disease is caused by heterozygous mutation in the ZBTB20 gene on chromosome 3q13.	Preferred (foundation metadata concept)
A rare genetic intellectual disability syndrome with characteristics of severe global developmental delay with intellectual disability, microcephaly, growth retardation, ocular defects such as congenital cataract and naevus flammeus simplex on the forehead. Cardiac, urogenital, and skeletal abnormalities, as well as seizures are present in most patients. Dysmorphic craniofacial features include sparse hair, downslanting palpebral fissures, hypertelorism, broad and overhanging nasal tip and short philtrum among others. The syndrome is caused by homozygous variants in the MED25 gene (19q13.33), coding for a component of the mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. Transmission is autosomal recessive.	Preferred (foundation metadata concept)
A rare genetic intestinal disease characterised by early-onset chronic non-infectious, non-bloody, watery diarrhoea associated with protein-losing enteropathy, which results in hypoalbuminaemia, hypogammaglobulinaemia and elevated stool alpha-1-antitrypsin. Patients typically present severe, intractable diarrhoea, failure to thrive, recurrent infections and oedema. There is evidence the disease is caused by homozygous mutation in the DGAT1 gene.	Preferred (foundation metadata concept)
A rare genetic intestinal disease with characteristics of early-onset chronic diarrhoea and intestinal inflammation due to overactivity of guanylate cyclase 2C. Additional manifestations include meteorism, dehydration, metabolic acidosis and electrolyte disturbances. Intestinal dysmotility, small-bowel obstruction and oesophagitis (with or without oesophageal hernia), as well as irritable bowel syndrome (without severe abdominal pain) and Crohn's disease are frequently associated. There is evidence the disease is caused by heterozygous mutation in the GUCY2C gene on chromosome 12p12.	Preferred (foundation metadata concept)
A rare genetic intestinal disease with the presence of multiple (usually large) hyperplastic/serrated colorectal polyps, usually with a pancolonic distribution. Histology reveals hyperplastic polyps, sessile serrated adenomas (most common), traditional serrated adenomas or mixed polyps. It is associated with an increased personal and familial (first-degree relatives) risk of colorectal cancer. There is evidence this disease is caused by heterozygous mutation in the RNF43 gene on chromosome 17q22.	Preferred (foundation metadata concept)
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 dystonia initially presenting as torticollis and later progressing to segmental or generalised 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 characterised 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 hyperbilirubinaemia 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 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 oesophagus 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 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 characterised by congenital cataracts, sensorineural hearing loss, severe psychomotor developmental delay, severe generalised 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 characterised, antenatally, by fetal akinesia, intrauterine growth restriction and polyhydramnios, and, following birth, by severe neonatal hypotonia, severe generalised 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 disorganisation 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), hypomineralisation 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 leucodystrophy identified in families of Ashkenazi Jewish descent, characterised 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 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 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 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, dyslipidaemia, 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 grey 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 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 characterised 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 generalised oedema, 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 seborrhoeic 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 characterised 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 hypercholesterolaemia 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 characterised by neonatal or early-infantile onset hepatopathy (manifesting with hepatomegaly, cholestasis, increased transaminases, coagulopathy, hypoalbuminaemia, 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 hypoglycaemia.	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 hypoglycaemia. 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 hyperuricaemia, hyponatraemia, hypomagnesaemia, hypochloraemic 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)

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Reference Sets

Reference set descriptor

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Id	Description	Lang	Type	Status	Case?	Module
900000000001112010	Great Britain 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)
900000000001113017	GB English	en	Synonym (core metadata concept)	Active	Entire term case sensitive (core metadata concept)	SNOMED CT model component module (core metadata concept)
900000000001114011	Great Britain 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)