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 very rare form of PCH with prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death. Has been reported in 10 families to date. Caused by a compound heterozygosity for p.A307S plus non-sense or splice site mutations in the TSEN54 gene. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5. Inherited in an autosomal recessive manner.	Preferred (foundation metadata concept)
A very rare form of acrofacial dysostosis, reported in four members of a family from the Sicilian village of Palagonia. The syndrome has characteristics of normal intelligence, shortness of stature, and mild acrofacial dysostosis (malar hypoplasia, micrognathia and webbing of digits with shortening of the fourth metacarpals) associated with oligodontia, normal or high arched palate, aplasia cutis verticis with pili torti, mild cutaneous syndactyly of digits 2-5, webbing of digits and shortening of the fourth metacarpals and unilateral cleft lip.	Preferred (foundation metadata concept)
A very rare form of acrofacial dysostosis, reported in two sisters to date, with characteristics of short stature, acrocephaly, ocular hypertelorism, ptosis of eyelids, ocular proptosis, downslanting palpebral fissures, high nasal bridge, anteverted nostrils, short philtrum, cleft palate, micrognathia, abnormal external ears, preauricular pits, mixed hearing loss, bulbous digits, metatarsus varus, pectus excavatum and various radiological abnormalities. Features of this syndrome were reported to overlap with otopalatodigital syndrome types 1 and 2. There have been no further descriptions in the literature since 1988.	Preferred (foundation metadata concept)
A very rare form of familial partial lipodystrophy of unknown aetiology characterised by loss of adipose tissue that is confined to the limbs and a normal or increased fat distribution of the face, neck, and trunk. Arterial hypertension and diabetes have also been associated	Preferred (foundation metadata concept)
A very rare form of focal palmoplantar keratoderma with characteristics of painful circumscribed hyperkeratotic lesions on weight-bearing areas of soles, moderate focal hyperkeratosis of palmar pressure-related areas and an asymptomatic leukokeratosis confined to labial and lingual attached gingiva. Additional occasional features may include hyperhidrosis, follicular keratosis and extended oral mucosa involvement.	Preferred (foundation metadata concept)
A very rare form of hereditary episodic ataxia with characteristics of late-onset episodic ataxia, recurrent attacks of vertigo and diplopia.	Preferred (foundation metadata concept)
A very rare form of hereditary episodic ataxia with characteristics of vestibular ataxia, vertigo, tinnitus and interictal myokymia.	Preferred (foundation metadata concept)
A very rare form of multiple endocrine neoplasia, an inherited cancer syndrome, with parathyroid and anterior pituitary tumours, possibly associated with adrenal, renal, and reproductive organ tumours. Caused by heterozygous inactivating mutations in the CDKN1B gene (12p13.1-p12) encoding p27, a cyclin-dependent kinase inhibitor that acts as a negative regulator of cell cycle progression. Most cases are the result of autosomal dominant inheritance. Some cases of sporadic de novo occurrence are however reported.	Preferred (foundation metadata concept)
A very rare form of stromal corneal dystrophy with characteristics of irregular amorphous sheet-like opacities in the posterior corneal stroma and in the Descemet membrane along with mildly impaired vision. Prevalence of this form of corneal dystrophy is not known. To date cases have been reported primarily in the USA. Patients usually develop corneal abnormalities in infancy or childhood. The condition is non-progressive or slowly progressive. Unlike other corneal dystrophies, non-corneal manifestations have been observed and include abnormalities of the iris including iridocorneal adhesions, corectopia, and pseudopolycoria. An autosomal dominant pattern of inheritance has been reported.	Preferred (foundation metadata concept)
A very rare form of superficial corneal dystrophy with characteristics of feather-shaped opacities and microcysts in the corneal epithelium arranged in a band-shaped and sometimes whorled pattern, occasionally with impaired vision. Exact prevalence of this form of corneal dystrophy is not known but very few cases have been reported to date. Lesions generally develop in childhood. Epithelial opacities are slowly progressive and painless blurred vision sometimes occurs after 60 years of age. The exact cause is unknown but appears to be genetic. The gene related to Lisch epithelial corneal dystrophy has been mapped to the short arm of the X chromosome (Xp22.3).	Preferred (foundation metadata concept)
A very rare form of superficial corneal dystrophy with characteristics of frequent recurrent corneal erosions in the first decade of life and progressive loss of vision. The condition has only been reported in one single family. Painful episodes of recurrent corneal erosions occur in the first decade of life but decrease during adolescence. Later in life, patients are reported to develop subepithelial opacities and a corneal haze. The disease eventually progresses over time leading to corneal opacities and loss of vision. The gene related to this disease has not been mapped to a particular chromosomal locus.	Preferred (foundation metadata concept)
A very rare genetic bone disorder with characteristics of ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive hearing loss in some patients.	Preferred (foundation metadata concept)
A very rare genetic disorder of water balance, closely resembling the far more frequent syndrome of inappropriate antidiuretic secretion (SIAD) characterised by hypotonic hyponatraemia due to impaired free water excretion and undetectable or low plasma arginine vasopressin (AVP) levels. Symptoms are the classical symptoms of hyponatraemic encephalopathy such as nausea, vomiting, dizziness and gait disturbances. Caused by a gain of function mutation in the type 2 AVP receptor (AVPR2) gene (location Xq28). This mutation leads to constant activation of the AVPR2 receptor on renal collecting duct cells, which causes an increase in free water reabsorption and an increase in urine concentration. An X-linked disorder affecting mainly males with females often being asymptomatic carriers.	Preferred (foundation metadata concept)
A very rare genetic disorder with characteristics of the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate and severe joint contractures. Less than 20 cases have been reported in the literature. The fingers are thin with absent knuckles and reduced creases over the joints and patients show an inability to make a full fist. Additional findings may include deformed ears, ptosis, an inability to open the mouth fully, heart defects, and clubfoot. There are currently no human genes associated with this disease.	Preferred (foundation metadata concept)
A very rare genetic disorder with clinical characteristics of elevated serum bile acid concentrations, itching and fat malabsorption reported in patients of Old Order Amish descent. Can be caused by mutation in the TJP2 gene on chromosome 9q21, the BAAT gene on chromosome 9q31, or the EPHX1 gene on chromosome 1q42.	Preferred (foundation metadata concept)
A very rare genetic malformation syndrome with characteristics of upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances and congenital bilateral non-progressive mixed hearing loss. Prevalence is not known. To date, four affected families from Venezuela, Italy, Hungary, and Turkey (discordant monozygotic twins) have been described. The syndrome has been linked to mutations in the SALL4 gene (20q13.2) encoding a transcription factor. Inherited in an autosomal dominant manner.	Preferred (foundation metadata concept)
A very rare genetic overgrowth/obesity syndrome with characteristics of macrocephaly, obesity, mental (intellectual) disability and ocular abnormalities. Other frequent clinical signs include macrosomia, downslanting palpebral fissures, hypertelorism, broad nasal root, high and broad forehead and delay in bone maturation, in association with normal thyroid function and karyotype.	Preferred (foundation metadata concept)
A very rare genetic vascular disease of autosomal recessive inheritance, described in less than 20 patients to date. The disease has manifestations of adult-onset (as early as the second decade of life) isolated calcification of the arteries of the lower extremities (including the iliac, femoral, and tibial arteries) as well as the capsule joints of the fingers, wrists, ankles and feet.	Preferred (foundation metadata concept)
A very rare gonadotropin-independent familial form of male-limited precocious puberty generally presenting between 2-5 years of age as accelerated growth, early development of secondary sexual characteristics and reduced adult height. Caused by an activating mutation of the Lutropin-Choriogonadotropic Hormone Receptor gene (LHCGR, 2p21) which leads to increased levels of sex steroids in the context of low luteinising hormone. This receptor's chronic activation leads to precocious testosterone production by Leydig cells. No effect is observed in female carriers due to the dual luteinising hormone (LH)/ follicle stimulating hormone (FSH) signal necessary to promote ovarian stimulation. Transmission is autosomal dominant. Mothers may act as silent carriers, with each son having a 50% chance of displaying this disorder.	Preferred (foundation metadata concept)
A very rare heart-hand syndrome that has characteristics of a variety of cardiovascular anomalies including patent arterial duct, bicuspid aortic valve and pseudocoarctation of the aorta in conjunction with hand anomalies such as brachydactyly and ulnar ray derivative i.e. fifth metacarpal hypoplasia. Transmission is most likely autosomal dominant although X-linked dominance could not be excluded.	Preferred (foundation metadata concept)
A very rare hepatic and biliary tract neoplasm with a growth pattern resembling that found in hepatocellular carcinomas and cholangiocarcinomas but presenting atypical histological and immunohistochemical features (such as trabecular, organoid, microcystic and/or blastemal-like architecture and inhibin A, cytokeratin 7 and/or cytokeratin 19 positivity) that do not allow a formal diagnosis of the more common aforementioned liver cancers. Patients may present abdominal distension and pain, a palpable abdominal mass and elevated liver enzymes.	Preferred (foundation metadata concept)
A very rare hereditary epidermal disorder characterised by hypotrichosis/woolly scalp hair, sparse body hair, eyelashes and eyebrows, leukonychia and striate palmoplantar keratoderma (more severe on the soles than the palms), which progressively worsens with age. Pseudo ainhum of the fifth toes was also reported. Although the syndrome shares clinical similarities with both Naxos disease and Carvajal syndrome, cardiomyopathy is notably absent. There is evidence the disease is caused by homozygous mutation in the KANK2 gene on chromosome 19p13	Preferred (foundation metadata concept)
A very rare hereditary neurological dysmorphic syndrome with characteristics of moyamoya disease, short stature of postnatal onset and stereotypical facial dysmorphism. The syndrome is extremely rare and has been reported in three unrelated families to date, with 10 affected individuals in several generations. These families are not from Japan or Asia, whereas in general the incidence of moyamoya disease is highest in Japan and other Asian countries, in comparison with other parts of the world. Affected patients are all male (X-linked inheritance) and have moyamoya angiopathy (progressive stenosis of the terminal portion of the intracranial internal carotid arteries), short stature, hypergonadotropic hypogonadism and other variable manifestations.. The genetic cause appears to involve Xq28 deletions removing MTCP1/CMC4 and BRCC3 (Xq28) .The specific pathophysiological mechanisms underlying this disorder remain obscure, but appear to involve alteration in DNA repair.	Preferred (foundation metadata concept)
A very rare hereditary skin disease with manifestation of irregularly distributed epidermal hyperkeratosis of the palms and soles. Reported in 35 families worldwide to date. The lesions usually start to develop in early adolescence but can also present later in life. Mutations in the AAGAB gene (15q22.33-q23) have recently been identified as one of the causes. Mutations in the COL14A1 gene (8q23) have also been identified as causal in some cases in Asia that seem to have a similar phenotype	Preferred (foundation metadata concept)
A very rare inborn error of metabolism disorder with a highly variable phenotype. Typical characteristics are neonatal to infancy-onset of seizures, psychomotor delay and abnormal muscle tone that may include hypo and/or hypertonia, resulting in generalised weakness, dystonic movements, and/or progressive respiratory distress, associated with severe lactic acidosis and elevated lactate, ketoglutarate and 2-oxoacids in urine. Additional manifestations may include dehydration, vomiting, signs of liver dysfunction, extrapyramidal signs, spastic tetraparesis, brisk deep tendon reflexes, speech impairment, swallowing difficulties and pulmonary hypertension. There is evidence the disease is caused by compound heterozygous mutation in the LIPT1 gene on chromosome 2q11.	Preferred (foundation metadata concept)
A very rare inborn error of mitochondrial fatty acid oxidation with characteristics of variable manifestations ranging from asymptomatic individuals to those with failure to thrive, hypotonia, seizures, developmental delay and progressive myopathy. In affected individuals manifestations include seizures, developmental delay (delayed sitting/walking and/or speech/social interaction), failure to grow with poor feeding and usually muscle weakness and hypotonia. Caused by mutations in the acyl-CoA dehydrogenase, C-2 to C-3 short chain ACADS gene (12q24.31) along with additional as yet unidentified precipitating factors. Inherited in an autosomal recessive manner.	Preferred (foundation metadata concept)
A very rare inherited connective tissue disorder with characteristics of macrocephaly, sparse scalp hair, soft redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rare manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly have also been reported. Caused by homozygous mutation in the RIN2 gene on chromosome 20p11.	Preferred (foundation metadata concept)
A very rare inherited form of thyroglossal duct cyst (TDC) with characteristics of a mass measuring 3cm in diameter or less in the midline area of the neck.	Preferred (foundation metadata concept)
A very rare inherited hair loss disorder with characteristics of sparse, fragile or absent hair on the scalp, eyebrows, eyelashes, axilla and rest of the body, associated with vesicle formation on various parts of the scalp and body which regularly burst and release watery fluid. Evidence suggests this syndrome is caused by homozygous mutation in the desmocollin-3 gene on chromosome 18q12.	Preferred (foundation metadata concept)
A very rare inherited malformation syndrome with characteristics of omphalocele, scoliosis, mild dysmorphic features (downslanted palpebral fissures, s-shaped eyelids and thin upper lip), laryngeal and pharyngeal hypoplasia and learning disabilities.	Preferred (foundation metadata concept)
A very rare kinetic eyelid anomaly that can affect the upper or lower eyelid, presents at birth, that in some cases can result in corneal exposure, and that may be associated with accessory levator muscle slips.	Preferred (foundation metadata concept)
A very rare lysosomal storage disease which is the normosomatic form of sialidosis with characteristics of gait abnormalities, progressive visual loss, bilateral macular cherry red spots and myoclonic epilepsy and ataxia, that usually presents in the second to third decade of life. The prevalence is unknown but it is less frequent than sialidosis type 2. This disease is due to a mutation of the N-acetyl-alpha-neuraminidase-1 (NEU1) gene (6p21) encoding the lysosomal enzyme neuraminidase that initiates the degradation of sialoglycoconjugates in lysosomes. Mutations lead to a decrease in enzyme activity and consequently to an accumulation of sialyloligosaccharides in tissues. Disease severity is linked to level of residual neuraminidase activity in vivo and varies between patients. Inherited in an autosomal recessive manner.	Preferred (foundation metadata concept)
A very rare lysosomal storage disease with characteristics of developmental delay of varying severity and hearing loss, but that can manifest a wide phenotypic heterogeneity.	Preferred (foundation metadata concept)
A very rare malformation syndrome with characteristics of hypoplasia of ulna associated with hypoplastic to absent fourth and/or fifth digits, hypoplasia of fibula, short stature and facial dysmorphism.	Preferred (foundation metadata concept)
A very rare malformation syndrome with characteristics of short stature, hypoplastic fifth digits with tiny dysplastic nails, facial dysmorphism with coarse features including a wide mouth and broad nose, and mild intellectual disability. It has been suggested that Coffin-Siris syndrome and BOD syndrome are perhaps allelic variants.	Preferred (foundation metadata concept)
A very rare malformation with main features of ectrodactyly of the hand and ipsilateral bifurcation of the femur. Approximately 200 cases have been reported worldwide. Congenital aplasia/hypoplasia of the tibia, accompanied by pre-axial oligodactyly or monodactyly of the feet, may also be present. In most cases, the bifurcation of the distal femur is unilateral. Patients are often small. Autosomal dominant and autosomal recessive modes of transmission have been suggested.	Preferred (foundation metadata concept)
A very rare malignant epithelial neoplasm of the pancreas composed of cystic structures lined by glycogen-rich clear cells, associated with local invasiveness often involving the spleen, duodenum and/or stomach and metastatic spread to the liver, peritoneum and/or lymph nodes. Presenting symptoms are variable and usually non-specific and include abdominal and/or flank pain, palpable abdominal mass, upper gastrointestinal bleeding, jaundice or abnormal serum liver enzymes, vomiting, anorexia and/or weight loss.	Preferred (foundation metadata concept)
A very rare malignant epithelial tumour of the pancreas characterised, macroscopically by a usually large well-circumscribed fully or partially encapsulated solid mass often with haemorrhage, necrosis and cystic changes in any portion of the pancreas. Histological characteristics are neoplastic cells with variable degrees of differentiation and morphology ranging from acinar structures similar to normal pancreatic acini to large sheets of poorly differentiated neoplastic cells. Presenting symptoms are typically non-specific and include abdominal pain, weight loss, vomiting, nausea, and/or less commonly jaundice. Immunohistochemical evidence of acinar-specific products is observed. Association with Lynch syndrome, familial adenomatous polyposis, and pancreatic panniculitis has been reported.	Preferred (foundation metadata concept)
A very rare mitochondrial disease with clinical characteristic of cardioencephalomyopathy resulting in death in infancy.	Preferred (foundation metadata concept)
A very rare mitochondrial respiratory chain deficiency described in fewer than 10 infants, primarily of middle Eastern descent, with clinical characteristics of transient but life-threatening liver failure with elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinaemia, and lactic acidaemia.	Preferred (foundation metadata concept)
A very rare motor neuron disease with characteristics of progressive upper motor neuron dysfunction leading to loss of the ability to walk with wheelchair dependence and subsequently, loss of motor speech production. Affected patients are usually normal at birth and have normal early development. During the second year of life, they lose the ability to walk (some patients never walk due to early severe spasticity) and then develop slowly progressive upper motor neuron disorders including pseudobulbar palsy and spastic quadriplegia. Other signs include clumsiness, muscle weakness and balance difficulties. Mutations in the ALS2 gene (2q33-q35) encoding alsin, a protein that is abundant in motor neurons, and less commonly mutations in the ERLIN2 gene (8p11.2) have been reported. Inherited in an autosomal recessive manner.	Preferred (foundation metadata concept)
A very rare movement disorder with characteristics of early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism. Disease presents in infancy to late childhood with one of two possible phenotypes: either generalised dystonia or dystonia-parkinsonism not responsive to L-Dopa. Dystonia usually starts in one limb, becomes generalised and mainly affects the trunk, neck and oromandibular muscles. Motor and speech developmental delays were also reported. The phenotypic spectrum of this disease is still being determined. Caused by mutations in the protein kinase, interferon-inducible double stranded RNA dependent activator (PRKRA) gene, located on chromosome 2q31.2. Inherited in an autosomal recessive manner.	Preferred (foundation metadata concept)
A very rare multiple congenital abnormality syndrome manifesting from birth with progressive hypertrichosis congenita terminalis (thick scalp hair extending onto the forehead with generalised increased body hair) associated with a typical acromegaloid facial appearance (thick eyebrows, prominent supraorbital ridges, broad nasal bridge, anteverted nares, long and large philtrum, and prominent mouth with full lips) appearing during childhood.	Preferred (foundation metadata concept)
A very rare multiple congenital anomalies syndrome described in four siblings and with characteristics of intellectual deficit, flat face and some skeletal features of Marfan syndrome such as tall stature, dolichostenomelia, arm span larger than height, arachnodactyly of hands and feet, little subcutaneous fat, muscle hypotonia and intellectual deficit.	Preferred (foundation metadata concept)
A very rare multiple congenital anomalies syndrome described in three brothers of one South-African family, and with features of hypospadias and intellectual deficit, in association with microcephaly, craniofacial dysmorphism, joint laxity and beaked nails	Preferred (foundation metadata concept)
A very rare multiple congenital anomalies syndrome with characteristics of limb deficiencies and renal anomalies that include split hand-split foot malformation, renal agenesis, polycystic kidneys, uterine anomalies and severe mandibular hypoplasia.	Preferred (foundation metadata concept)
A very rare multiple congenital anomalies syndrome with short stature, facial dysmorphism (elongated face, hypertelorism, broad and high nasal bridge, mild epicanthus, posteriorly angulated ears, narrow and high-arched palate), skeletal anomalies (mesomelic brachymelia, short broad hands, prominent finger pads, short stubby thumbs, hyperextensibility of small joints, small feet), hypernasality and normal intelligence. Delayed bone age has also been reported.	Preferred (foundation metadata concept)
A very rare multiple congenital anomaly syndrome with characteristics of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities. An autosomal recessive inheritance has been suggested.	Preferred (foundation metadata concept)
A very rare multiple congenital anomaly syndrome. The syndrome has characteristics of bifid nose (with bulbous nasal tip but not associated with hypertelorism) with or without the presence of anal defects (i.e. anteriorly placed anus, rectal stenosis or atresia) and renal dysplasia (unilateral or bilateral renal agenesis) and without intellectual disability. BNAR syndrome is phenotypically related to Fraser syndrome and oculotrichoanal syndrome.	Preferred (foundation metadata concept)
A very rare multisystem neurodegenerative disorder characterised by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells, and neuronal loss. Infantile, juvenile, and adult-onset cases have been described. As any part of the nervous system can be affected (central, peripheral, and autonomic nervous systems), the clinical manifestations depend on the sites involved, and widely vary. The most common neurological signs include ataxia, extra-pyramidal signs (tremor and oculogyral crises), lower motor neuron findings (absent deep tendon reflexes, weakness, muscle wasting, foot deformities), and less apparent behavioural or cognitive difficulties. Most cases are sporadic.	Preferred (foundation metadata concept)
A very rare neonatal epileptic encephalopathy disorder with clinical characteristics of myoclonic and clonic, or clonic seizures associated with apnoea occurring several hours to 5 days after birth and responding to folinic acid.	Preferred (foundation metadata concept)
A very rare neoplasm of the pineal region that is thought to arise from the specialised ependymocytes of the subcommissural organ and that manifests with visual disturbances, headaches, loss of coordination and balance, nausea and vomiting due to obstructive hydrocephalus.	Preferred (foundation metadata concept)
A very rare non-syndromic autosomal recessive pyridoxine-refractory sideroblastic anaemia due to a splice defect of glutaredoxin-5 (GLRX5) described in a single patient with adult onset microcytic hypochromic anaemia with liver iron overload and type 2 diabetes.	Preferred (foundation metadata concept)
A very rare progressive and untreatable disease with manifestations of ataxia with sensory neuropathy. Prevalence is unknown, typically starts in middle-aged adults and presents with cerebellar ataxia, pyramidal signs, and peripheral sensory loss. The disease has been linked to chromosome 16q22.1 in kindreds from Utah (USA) and Germany but the mutation is yet unknown and does not appear to involve trinucleotide repeats.	Preferred (foundation metadata concept)
A very rare pure form of spastic paraplegia with characteristics of onset in infancy of lower limb spasticity associated with gait disturbances, scissor gait, tiptoe walking, clonus and increased deep tendon reflexes. Mild upper limb involvement may occasionally also be associated.	Preferred (foundation metadata concept)
A very rare recessive X-linked biogenic amine metabolism disorder with clinical characteristics of mild intellectual deficit, impulsive aggressiveness, sometimes violent behaviour and presenting from childhood.	Preferred (foundation metadata concept)
A very rare secondary neonatal autoimmune disease characterised by generalised weakness, severe hypotonia, absent or reduced deep tendon reflexes and highly elevated serum creatine kinase levels presenting in the neonatal period. Perifascicular atrophy in the presence of a diffuse perivascular inflammatory cell exudate is observed on muscle biopsy.	Preferred (foundation metadata concept)
A very rare secondary neonatal autoimmune disease characterised by onset of haemolytic anaemia in the neonatal period associated with a positive direct antiglobulin test. Hepatosplenomegaly may be associated.	Preferred (foundation metadata concept)
A very rare secondary neonatal autoimmune disease with characteristics of neonatal-onset of erythematous skin lesions with a linear appearance that gradually become indurated and hyperpigmented and progressively present skin atrophy. Positive serum antibodies (in particular antinuclear antibodies and/or rheumatoid factor) may be associated.	Preferred (foundation metadata concept)
A very rare severe motor neuron disease with manifestation of progressive upper and lower motor neuron degeneration causing facial spasticity, dysarthria, and gait disorders with onset before 25 years of age. The disease is usually slowly progressive and some patients have been reported to become bedridden by 12 to 50 years of age. Mutations in the following genes have been found in patients ALS2 (2q33-q35), and rarely SIGMAR1 (9p13.3), SPG11 (15q13-q15) and FUS (16p11.2).	Preferred (foundation metadata concept)
A very rare severe non-syndromic hypochromic anaemia, which is characterised by transfusion-dependent hypochromic, poorly regenerative anaemia, iron overload, resembling non-syndromic sideroblastic anaemia except for increased erythrocyte protoporphyrin levels. It has been reported in 3 siblings to date. Caused by a nonsense heterozygous mutation in the STEAP3/TSAP6 gene. Transmission is most likely recessive with a low expression allele.	Preferred (foundation metadata concept)
A very rare slowly progressive form of neurodegeneration with brain iron accumulation (NBIA) with characteristics of classic NBIA features. The clinical manifestations include early-onset spastic-dystonic paraparesis, oromandibular dystonia, dysarthria, parkinsonism, axonal neuropathy, progressive cognitive impairment, complex motor tics, and obsessive-compulsive disorder. The disease is caused by homozygous or compound heterozygous mutation in the COASY gene on chromosome 17q21.	Preferred (foundation metadata concept)
A very rare subtype of Joubert syndrome and related disorders with characteristics of neurological features of Joubert syndrome associated with orofacial anomalies and often polydactyly. Prevalence is unknown. Typical oral findings include bifid or lobulated tongue, lingual hamartomas and multiple oral frenula, but cleft lip and/or palate can also be present. Two OFD6 patients, including one fetus, were found to carry a homozygous mutation in the TMEM216 gene (11q13.1), but mutations in this gene were excluded in several other patients and the genetic basis of this condition still remains elusive.	Preferred (foundation metadata concept)
A very rare subtype of Joubert syndrome with the neurological features of Joubert Syndrome and congenital hepatic fibrosis. Prevalence is unknown. The age of onset and severity of hepatic manifestations are variable. Some patients may also present chorioretinal or optic nerve colobomas and nephronophthisis but these are not mandatory features. Over 70% of cases are due to mutations in the TMEM67 gene (8q22.1).	Preferred (foundation metadata concept)
A very rare subtype of autosomal dominant cerebellar ataxia type 3 with characteristics of late-onset and slowly progressive cerebellar signs (gait ataxia) and eye movement abnormalities. To date, only 23 affected patients have been described from one American family of Norwegian descent. Disease onset occurs between the ages of 26-60. A candidate gene has recently been identified as the eukaryotic translation elongation factor 2 (EEF2) gene, located on chromosome 19p13.3. Inherited autosomal dominantly.	Preferred (foundation metadata concept)
A very rare subtype of dystrophic epidermolysis bullosa with characteristics of blistering confined primarily to the hands and feet. The disease usually manifests during infancy with trauma-induced blisters limited to extremities. Healing of blisters is associated with milia formation, atrophic scarring and dystrophic nails. There is no extracutaneous involvement. Caused by mutations within the type VII collagen gene (COL7A1). Mutations in this gene lead to an alteration in function of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis. Transmission is autosomal dominant (acral dominant dystrophic epidermolysis bullosa) or autosomal recessive (acral recessive dystrophic epidermolysis bullosa).	Preferred (foundation metadata concept)
A very rare subtype of type I autosomal dominant cerebellar ataxia with cerebellar dysarthria as the initial typical manifestation. Prevalence is unknown. Fewer than 20 cases in a 4-generation Australian family of Anglo-Celtic descent have been reported to date. Age of symptomatic disease onset ranges from 19 to 64 years. Linked to chromosome 11q12.2-11q12.3.	Preferred (foundation metadata concept)
A very rare subtype of type I autosomal dominant cerebellar ataxia with characteristics of cerebellar ataxia and prominent sensory neuropathy. Fewer than 10 cases in a 4-generation French family have been reported to date. Age of onset ranges from 1 to 39 years. The clinical features vary widely from sensory neuropathy with little cerebellar ataxia to cerebellar ataxia with little sensory neuropathy. Some patients exhibit gastrointestinal disorders such as vomiting and abdominal pain as initial symptoms. Scoliosis and urinary problems are also observed. Maps to chromosome 2p15-p21.	Preferred (foundation metadata concept)
A very rare subtype of type I autosomal dominant cerebellar ataxia with characteristics of gait ataxia, dysarthria, slowed saccades, ocular dysmetria, Babinski sign and hyperreflexia. This subtype has only been described in 4 Dutch families. Age of onset is from 43 to 56 years. Maps to chromosome region 20p12.3-p13 and missense mutations in the prodynorphin PDYN gene appear to cause the disease.	Preferred (foundation metadata concept)
A very rare subtype of type I autosomal dominant cerebellar ataxia with characteristics of slowly progressive cerebellar ataxia, mild cognitive impairment, postural and or resting tremor, bradykinesia, and rigidity. Prevalence is unknown. Fewer than 20 cases in a 4-generation French family have been reported to date. Maps to chromosome 7p21.3-p15.1 but the gene and gene mutation have not been identified.	Preferred (foundation metadata concept)
A very rare syndrome associating an acro-fronto-facio-nasal dysostosis with genitourinary anomalies. It has been described in three families. Craniofacial manifestations include wide anterior fontanelle, flat occiput, hypertelorism, ptosis, proptosis, broad nasal bridge and nasal tip, long philtrum and posteriorly rotated or low set ears. Hypospadias and shawl scrotum are present in all males. Acral manifestations include syndactyly of fingers, broad thumbs or halluces or preaxial polydactyly. The affected patients have no intellectual deficit. The condition seems to be hereditary, and transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome associating bone dysplasia with micromelic dwarfism and eye defects. It has been reported in a father and his son. Bone dysplasia has characteristics of diaphyseal thickening of the long bones, metaphyseal deformation and epiphyseal irregularities. Eye defects consisted of myopia, microspherophakia, lens coloboma and luxation and retinal detachment. The affected patients have normal mental development.	Preferred (foundation metadata concept)
A very rare syndrome associating microcephaly, micrognathia, oculocutaneous albinism, hypoplasia of the distal phalanx of fingers and agenesia of the distal end of the right big toe. It has been described in two siblings. Both brother and sister had psychomotor retardation and died in the course of a respiratory infection. The reported cases suggest that the condition is hereditary, and is transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome characterised by poorly mineralised calvarium, facial dysmorphism, vertebral abnormalities and absent clavicles. Nine cases have been reported in the literature so far. Dysmorphic features include micrognathia, cleft palate, hypertelorism and upturned nares. Clavicular aplasia is constant and agenesis of cervical vertebral bodies is frequent. Intra uterine growth retardation is constant. It is most likely that the condition is hereditary, transmitted as an autosomal recessive trait. Prognosis is poor, the syndrome is almost always lethal soon after birth.	Preferred (foundation metadata concept)
A very rare syndrome characterised by the association of multinodular goitre, cystic renal disease and digital anomalies. It has been described in two siblings and one unrelated child. The two siblings had digitalised thumbs and preaxial polydactyly, the third child had normal thumbs and postaxial polydactyly. Goitre and/or digitalised thumbs and/or polydactyly were present in other members of families. This syndrome seems to be transmitted as an autosomal dominant trait with variable expression and incomplete penetrance.	Preferred (foundation metadata concept)
A very rare syndrome consisting of microcephaly with facial dysmorphism, spondylometaphyseal dysplasia and severe intellectual deficit. Eight cases have been reported in the literature in two unrelated families. Dysmorphic features include hypertelorism, depressed nasal bridge, and large nose with a large nasal tip, anteverted nostrils and wide mouth with thick lips. Affected patients do not achieve language ability. The condition is probably hereditary, and transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome consisting of short stature, facial dysmorphism, hypospadias and mixed hearing loss. It has been reported in two brothers. Dysmorphic features include hypertelorism, upper lid coloboma, midface hypoplasia, saddle nose deformity with a midline nasal cleft, thick philtrum and everted lower lip. The two brothers had developmental delay.	Preferred (foundation metadata concept)
A very rare syndrome described in four siblings of one French family and with characteristics of branchial dysplasia (malar hypoplasia, macrostomia, preauricular tags and meatal atresia), club feet, inguinal hernia and cholestasis due to paucity of interlobular bile ducts and intellectual deficit.	Preferred (foundation metadata concept)
A very rare syndrome described in three siblings of one Japanese family with main features of congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, and relatively dark skin and typical dermatoglyphic anomalies, and intellectual deficit.	Preferred (foundation metadata concept)
A very rare syndrome described in two siblings with manifestation of prenatal onset of growth deficiency, microcephaly, hypoplastic genitalia, and birth onset of convulsions.	Preferred (foundation metadata concept)
A very rare syndrome including short stature, facial dysmorphism, hand abnormalities and shawl scrotum. It has been observed in 16 subjects from five distantly related sibships of a large Kuwaiti Bedouin tribe. The affected patients had no intellectual deficit. Transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome of congenital hypothyroidism with characteristics of thyroid dysgenesis, cleft palate and spiky hair, with or without choanal atresia, and bifid epiglottis. Facial dysmorphism and porencephaly have been reported in isolated cases. Only 8 patients from 6 families have been reported to date. Newborns present at birth with thyroid dysgenesis (in most cases athyreosis) leading to congenital hypothyroidism that manifests with lethargy, poor feeding, macroglossia, cold or mottled skin, persistent jaundice and umbilical hernia. All newborns have a cleft palate and spiky hair. The syndrome is due to homozygous loss-of-function missense mutations located within the forkhead domain of the FOXE1 gene (9q22), encoding thyroid transcription factor 2 (TTF-2). TTF-2 is expressed in the thyroid gland (as well as elsewhere like the tongue, epiglottis and palate) and is thought to play a crucial role in thyroid morphogenesis. The disease is inherited autosomal recessively.	Preferred (foundation metadata concept)
A very rare syndrome that presents with short and sparse scalp hair from birth or the first months of life with no subsequent growth during life. During the first to third decades of life, visual acuity decreases because of progressive macular degeneration, leading in many cases to blindness between the second and fourth decades of life. The hair phenotype does not improve significantly with age, even though diffuse alopecia in infancy can evolve towards short and sparse hair in puberty. Caused by mutations in the CDH3 gene (16q22.1), encoding P-cadherin. P-cadherin is part of adherens junctions in various epithelia including the hair follicular epithelium. Inherited in an autosomal recessive pattern.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of blepharophimosis, arachnodactyly, joint contractures and dysmorphic features. Ten cases from seven families have been reported in the literature. The dysmorphic features include narrow nose with hypoplastic alae nasi, hypoplastic maxilla, everted lower lip, blepharophimosis, large ears and high-arched or cleft palate. The affected patients can have learning disabilities. The condition is transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of intellectual deficit, horseshoe kidney, and congenital heart defects. Four cases have been reported in the literature in two unrelated families. Dysmorphic features include plagiocephaly, malar hypoplasia, broad nasal bridge, poorly developed philtrum and nasal alae, cleft palate and hypodontia. Congenital heart defects were endocardial fibroelastosis in one family and prolapse of the tricuspid valve in the other. The condition is probably hereditary and transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of intellectual deficit, postaxial polydactyly and epilepsy. To date, seven individuals in three families have been reported. Facial features are not characteristic except for a prominent jaw. Concordant features in all subjects are postaxial polydactyly, which in four individuals affect also the feet, and intellectual deficit, which is usually severe, with absent or indistinct speech. Seizures are common with onset in the first months of life or in early childhood. Cutaneous syndactyly, camptodactyly and clinodactyly of fingers and brachydactyly and syndactyly of the toes have been recorded.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of mesomelic shortness of the forearms, bilateral clubfeet, aplasia or hypoplasia of all nails and severe psychomotor retardation. It has been reported in two siblings. The family is suggestive of autosomal recessive inheritance. Prognosis is poor.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of microcephaly, craniosynostosis, glaucoma, growth failure and visceral malformations. Only three cases have been reported in the literature in three unrelated families. Dysmorphic features include trigonocephaly, exotropia, cleft palate, beaked nose and low-set ears. All the affected patients have associated congenital visceral malformations including congenital heart defects, diaphragmatic hernia, genital or cerebral abnormalities. The demonstration of congenital glaucoma, hallmark of the syndrome, in the father of an affected patient, supports autosomal dominant inheritance. Prognosis is poor.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of progressive loss of bone usually of the carpal and tarsal bones resulting in deformity and disability and accompanied by chronic renal failure in many cases. The bone and renal disorders are sometimes associated with intellectual deficit and facial abnormalities. There is evidence the disease is caused by heterozygous mutation in the MAFB gene on chromosome 20q12.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of the association of Mobius syndrome (congenital facial palsy with impaired ocular abduction) with peripheral axonal neuropathy and hypogonadotropic hypogonadism. All of the reported cases were sporadic.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of the combination of hypertelorism, cleft lip and palate and microtia. Nine cases have been reported in the literature in seven families. Some patients have associated cardiac or renal congenital malformations. Short stature and intellectual deficiency are common. The reported cases support autosomal recessive inheritance.	Preferred (foundation metadata concept)
A very rare syndrome with characteristics of unilateral complete or partial lung agenesis, congenital cardiac defects and ipsilateral thumb anomalies. It has been described in 7 patients. Cardiac abnormalities are variable and mainly consist of atrial septal defect, anomalous pulmonary venous return or patent ductus arteriosus. Thumb anomalies include triphalangeal, proximally placed, hypoplastic or reduplicated thumb. One patient had a preaxial polydactyly with a rudimentary thumb. Other malformations can be also observed. The affected patients have normal intellectual development.	Preferred (foundation metadata concept)
A very rare syndrome with the association of gingival fibromatosis and craniofacial dysmorphism. It has been described in two siblings. Craniofacial dysmorphism consists of relative macrocephaly, bushy eyebrows with synophrys, hypertelorism, downslanting palpebral fissures, flattened nasal bridge and high arched palate. The patients have normal intellect.The condition seems to be hereditary, transmitted as an autosomal recessive trait.	Preferred (foundation metadata concept)
A very rare syndrome with the association of limb pterygia, heart anomalies, autosomal recessive inheritance, vertebral defects, ear anomalies and radial defects. It has been described in two siblings. One of the siblings also had a myelomeningocele. The reported cases suggest the condition is hereditary with probable autosomal recessive inheritance.	Preferred (foundation metadata concept)
A very rare syndrome with the association of thin and short upper and lower tarsus and absence of the lower eyelashes. It has been described in 11 patients from a four-generation family. There is no other unusual feature. Inheritance is autosomal dominant.	Preferred (foundation metadata concept)
A very rare syndrome with the combination of microcephaly, heart defects, renal hypoplasia, lung segmentation defects and cleft palate. It has been described in three female siblings. Dysmorphic features were not characteristic. The condition seems to be hereditary, and transmitted as an autosomal recessive trait. Prognosis is poor and all children died in infancy.	Preferred (foundation metadata concept)
A very rare syndromic genetic deafness with characteristics of mild to moderate conductive hearing loss, dysmorphic pinnae and lip pits or dimples. The pinnae are usually small, cup-shaped with helix folded forward, and hearing loss is associated with malformed ossicles and displacement of the external auditory canal.	Preferred (foundation metadata concept)
A very rare syndromic limb malformation described in two distantly related boys. Its features are described as absence deformity of the left leg, progressive scoliosis, short stature, congenital cataract associated with dysplasia of the optic nerve. No intellectual deficit has been observed.	Preferred (foundation metadata concept)
A very rare tricarboxylic acid cycle disorder resulting from a deficiency in alpha-ketoglutarate dehydrogenase (one of the three subunits of the alpha-ketoglutarate dehydrogenase complex), that most often presents in the neonatal period with hypotonia, severe encephalopathy, extrapyramidal signs, pyramidal tract dysfunction and seizures and that frequently results in death in early childhood. Metabolic acidosis, elevated lactate and glutamate levels and variable degrees of glutaric aciduria are noted. Sudden death, myocardiopathy, and hepatic disorders have also been reported in some cases.	Preferred (foundation metadata concept)
A very rare tumour of the intestine, originating from the epithelium of the anal canal (including the mucosal surface, anal glands, and lining of fistulous tracts), macroscopically appearing as a nodular, often ulcerated, invasive mass located in the anal canal. Patients often present with rectal bleeding, as well as difficulty and pain during defaecation. Inguinal lymphadenopathy, if present, usually indicates metastatic spread.	Preferred (foundation metadata concept)
A very rare type of acrofacialdysostosis with characteristics of mild intrauterine growth retardation, postnatal short stature, microcephaly, widow's peak, mandibulofacial dysostosis without cleft palate, frequent caries, mild pre and postaxial limb hypoplasia with brachydactyly, mild interdigital webbing, simian creases, inguinal hernia and cryptorchidism and hypospadias in males.	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)