TaoMedAI/RareMedData huggingface dataset:
Vitamin B12-unresponsive methylmalonic acidemia type mut0 (ORPHA:289916)
Vitamin B12-unresponsive methylmalonic acidemia type mut0 is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.
Epidemiology
Prevalence of this disorder is not known.
Clinical description
The disease typically presents very early in life (<1 to 4 weeks), although rare later onset cases have been observed, with features including lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress, muscle hypotonia, developmental delay, intellectual deficit, hepatomegaly and coma. Patients may show signs of anemia. They may also have potentially life-threatening ketoacidosis and/or hyperammonemia, renal and neurological complications, metabolic stroke and cardiomyopathy.
Etiology
The disease is caused by complete deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase which is a result of mutations in the MUT gene (6p21).
Genetic counseling
It is transmitted as an autosomal recessive trait.

                            Last update: 
                            February 2012


                            - Expert reviewer(s): 
                            Dr David ROSENBLATT  - Dr David WATKINS
Vitamin K antagonist embryofetopathy (ORPHA:1914)
Vitamin K antagonist embryofetopathy is characterized by a group of symptoms that may be observed in a fetus or newborn when the mother has taken oral vitamin K antagonists, such as warfarin during pregnancy. Vitamin K antagonists are anticoagulant drugs that provide efficient thromboprophylaxis and that can cross the placenta. 5-12 % of infants exposed to warfarin between 6-9 weeks gestation present nasal hypoplasia and skeletal abnormalities, including short limbs and digits (brachydactyly), and stippled epiphyses. Warfarin fetopathy with central nervous system abnormalities (hydrocephalus, intellectual disability, spasticity, and hypotonia) or ocular abnormalities (microphthalmia, cataract, optic atrophy), fetal loss, and stillbirth, occurs in infants exposed at later gestations. Additional features that have been reported after in utero warfarin exposure include facial dysmorphism (cleft lip and/or palate, malformed ears), choanal atresia or stenosis, aorta coarctation, situs inversus totalis, bilobed lungs, and ventral midline dysplasia.
Vogt-Koyanagi-Harada disease (ORPHA:3437)
Vogt-Koyanagi-Harada disease is a bilateral, chronic, diffuse granulomatous panuveitis typically characterized by serous retinal detachment and frequently associated with neurological (meningitis), auditory, and dermatological alterations.
Epidemiology
Annual incidence is estimated at 1/400,000. The condition predominantly affects young women and individuals with darker pigmentation (those of Asian, Hispanic, or Native American origin). Children may be affected, but the mean age of onset is about 30 years of age (ranging from 10 to 52 years).
Clinical description
The most common clinical manifestations are headaches (67% of cases), ocular involvement with panuveitis, skin vitiligo, alopecia, and inner ear disturbances. The disease can be divided into four clinical stages. The prodromic stage is characterized by nonspecific symptoms such as fever, headaches, nausea and vertigo, and then by neurologic symptoms such as muscle weakness, hemiparesis, hemiplegia, dysarthria and orbital pain. In the ophthalmologic stage, occurring a few days after the prodromic stage, patients complain of blurred vision, ocular pain, and photophobia or central scotoma (bilateral in 80% of cases). Bilateral, serous, non-rhegmatogenous retinal detachment often occurs. Hearing disturbances (75%) and dizziness may also be present. The convalescent stage, occurring within three months of disease onset, is characterized by the apparition of cutaneous signs such as poliosis involving the eyebrows and eyelashes (and sometimes the scalp and body hair), hair loss, and vitiligo (usually perilimbal). Recurrent uveitis and ophthalmologic complications appear in the final stage, the chronic recurrent stage.
Etiology
Pathogenesis has been linked to immunological disorders targeting the melanocytes, and which involve T-cell-mediated cytotoxicity and apoptosis. However, the etiology is still not completely understood. An association between disease susceptibility and positive blood tests for the HLA-DRB1*0405 haplotype has been reported.
Diagnostic methods
Diagnosis is clinical. Cerebrospinal fluid analysis revealing pleocytosis can confirm the diagnosis.
Management and treatment
Management should involve a multidisciplinary team with dermatologists, ophthalmologists, and neurologists. High doses of corticosteroids usually provide efficient treatment, but immunosuppressors may also be used.
Prognosis
With early and aggressive treatment, the prognosis is usually favorable, but acute hearing and vision alterations may occur.

                            Last update: 
                            March 2009


                            - Expert reviewer(s): 
                            Dr Olivier CALVETTI  - Dr Caroline LAURENT-CORIAT  - Pr Michel PAQUES
Von Voss-Cherstvoy syndrome (ORPHA:3439)
Von Voss-Cherstvoy syndrome is a very rare disorder with phocomelia of upper limbs, encephalocele, variable brain anomalies, urogenital abnormalities, and thrombocytopenia.
Epidemiology
Less than 15 cases have been reported.
Clinical description
The spectrum of upper limb defects varies from radial agenesis and phocomelia to amelia. A meningoencephalocele is constant. The intellectual development may be normal.
Etiology
Pathogenesis and cause of this syndrome are unknown.
Genetic counseling
Parental consanguinity reported in a family suggests an autosomal recessive pattern of inheritance.

                            Last update: 
                            May 2010
Von Willebrand disease type 2A (ORPHA:166084)
A subtype of type 2 von Willebrand disease characterized by a bleeding disorder associated with a decrease in the affinity of the Willebrand factor (VWF) for platelets and the subendothelium caused by a deficiency of high molecular weight VWF multimers. The disease manifests as mucocutaneous bleeding (menorrhagia, epistaxis, gastrointestinal hemorrhage, etc.).
Von Willebrand disease type 2B (ORPHA:166087)
A subtype of type 2 von Willebrand disease characterized by a bleeding disorder associated with increased affinity of the Willebrand factor (VWF) for platelets leading to rapid clearance of both the platelets (increasing the risk of thrombocytopenia) and VWF from the plasma. The disease manifests as mucocutaneous bleeding (menorrhagia, epistaxis, gastrointestinal hemorrhage, etc.).
Von Willebrand disease type 2M (ORPHA:166090)
A subtype of type 2 von Willebrand disease characterized by a bleeding disorder associated with decreased affinity of the Willebrand factor (VWF) for platelets or collagen in the absence of any deficiency of high molecular weight VWF multimers. The disease manifests as mucocutaneous bleeding (menorrhagia, epistaxis, gastrointestinal hemorrhage, etc.).
Von Willebrand disease type 2N (ORPHA:166093)
A subtype of type 2 von Willebrand disease characterized by a bleeding disorder associated with a marked decrease in the affinity of the Willebrand factor (VWF) for factor VIII (FVIII). Abnormal bleeding manifestations are less frequent in this VWD subtype than in other forms of the disease. The disease manifests mainly as soft tissue bleeding (haematoma, post-operative bleeding, etc.).
VPS11-related autosomal recessive hypomyelinating leukodystrophy (ORPHA:466934)
A rare genetic leukodystrophy identified in families of Ashkenazi Jewish descent, characterized by infancy onset of severe global developmental delay with very limited or absent speech and sometimes complete absence of motor development, hypotonia, spasticity, and acquired microcephaly. Seizures, hearing loss, visual impairment, and autonomic dysfunction have also been described. Brain imaging shows delayed myelination and other white matter abnormalities.
Vulvar adenocarcinoma (ORPHA:494454)
A rare vulvar carcinoma characterized by a malignant epithelial neoplasm of glandular origin and/or with glandular characteristics arising in the vulva, including adenocarcinoma of mammary gland type, sweat gland type, and intestinal type, as well as adenocarcinomas of the Bartholin glands and Paget disease of the vulva. Depending on the type of tumor and disease stage, patients may present with a solitary vulvar mass, bleeding, or (in the case of Paget disease) a pruritic, erythematous, eczematous lesion.
Vulvar basal cell carcinoma (ORPHA:494451)
A rare vulvar carcinoma characterized by a slowly growing ulcer or nodule which is histologically composed of demarcated nests of palisaded basal cells originating at the epidermal-dermal junction. Occasionally, the tumor may be extensively pigmented. Patients most commonly present with pruritus. The lesion is usually treated by local excision, although groin metastases have been reported.
Vulvar carcinoma (ORPHA:494418)
A group of rare tumors of the vulva comprising HPV-associated and HPV-independent squamous cell carcinomas as the most frequent malignant vulvar tumors, basal cell carcinomas, adenocarcinomas, and Bartholin gland carcinomas. Depending on the type of tumor and disease stage, patients may present with a painless vulvar mass or ulcer, or with pruritus, a burning sensation, pain, or bleeding.
Vulvar intraepithelial neoplasia (ORPHA:137583)
A rare vulvovaginal tumor characterized by intraepithelial neoplastic proliferation of the vulvar epithelium, histologically presenting proliferation of atypical basal cells with basal layer involvement, enlarged nuclei, hyperchromasia, pleomorphic cells and increased numbers of mitotic figures. Patients are frequently asymptomatic, although vulvar pruritus/pain/burning, dysuria and/or dyspareunia may be associated. Concurrent anogenital involvement is frequent. Two subtypes, usual type VIN (uVIN) and differentiated type VIN (dVIN) exist, with uVIN typically being associated with HPV infection and presenting multifocal, elevated lesions around the introitus and/or labia majora, and dVIN being related to chronic inflammation and lesions consisting of poorly demarcated pink or white plaques that are often associated with lichen sclerosus or lichen planus. Diffusely positive p16 immunohistochemistry and high Ki-67 proliferation index in uVIN futher differentiates this subtype from dVIN, this latter being consistently negative for p16 while presenting p53 positivity.
Vulvar squamous cell carcinoma (ORPHA:494448)
A rare vulvar carcinoma characterized by an ulcer, nodule, macule, or pedunculated mass which is histologically composed of infiltrating islands of malignant squamous cells. Histological subtypes include keratinizing, non-keratinizing, basaloid, warty, and verrucous carcinomas. Some tumors are associated with human papilloma virus, smoking, high grade squamous intraepithelial lesion, chronic vulvar inflammatory disorders, or differentiated vulvar intraepithelial neoplasia. Patients may present with discharge, bleeding, or pain. Most important prognostic features are tumor depth and lymph node status.
Vulvovaginal gingival syndrome (ORPHA:83453)
A rare, non-malformative vulvovaginal disease characterized by a combination of erosive or desquamative lichen planus (LP) of vulval, vaginal and gingival mucosae, with a high propensity for scarring and stricture formation. Additional sites of involvement are frequently observed (in particular, tongue, buccal mucosae, skin and perianal LP). Patients may be asymptomatic or, more commonly, present with pain, burning, discomfort and bleeding, dyspareunia, and seropurulent vaginal discharge.
Vulvovaginal rhabdomyosarcoma (ORPHA:206492)
Vulvovaginal rhabdomyosarcoma is a rare vulvovaginal tumour, a highly malignant soft tissue sarcoma composed of cells with round to oval or spindle-shaped nuclei and eosinophilic cytoplasm that may show differentiation towards striated muscle cells. It usually affects children and presents with a vulvar or vaginal mass that may be polypoid or grape-like (embryonal subtype) and associated with bleeding and ulceration.
W syndrome (ORPHA:2804)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by moderate to severe intellectual disability, neurologic signs and symptoms (such as seizures, spasticity, strabismus), characteristic dysmorphic facial features (including broad forehead, hypertelorism, downslanting palpebral fissures, broad and flat nasal bridge, midline notch of upper lip, lack of upper central incisors, incomplete oral cleft, and prominent mandible), and acne scars. Hearing impairment, pseudo-bulbar palsy, growth retardation, and skeletal anomalies (camptodactyly, clinodactyly, bilateral cubitus valgus, pes cavus/planus) have also been described.
Waardenburg syndrome type 1 (ORPHA:894)
A subtype of Waardenburg syndrome (WS) characterized by congenital deafness, minor defects in structures arising from neural crest resulting in pigmentation anomalies of eyes, hair, and skin, in combination with dystopia canthorum.
Epidemiology
The prevalence of WS1 is unknown; the worldwide prevalence of WS is estimated at around 1/40,000. WS1 is one of the most common types of WS.
Clinical description
Clinical manifestations vary within and between families and frequently include congenital sensorineural deafness, which is often a non-progressive profound bilateral hearing loss, dystopia canthorum, heterochromic or hypoplastic blue irides, white forelock, typically in the midline or early graying of the scalp hair before age 30 years. All these manifestations along with a suggestive family history are major criteria. Minor criteria include congenital leukoderma, synophrys/medial eyebrow flare, broad/high nasal root with prominent columella, hypoplastic alae nasi. Spina bifida can also occur in rare cases.
Etiology
WS is genetically heterogeneous. WS1 is caused by a heterozygous mutation in the paired box-containing PAX3 gene on chromosome 2q36.1. This syndrome is secondary due to the absence of melanocytes in the skin, hair, eyes and the striavascularis ductus cochlearis and a consequence of abnormal migration of cells derived from the neural crest.
Diagnostic methods
Over 90% of cases who meet diagnostic criteria for WS1 have identifiable mutations in PAX3. WS1 is defined by the association of at least 2 major, or 1 major and at least 2 minor clinical criteria, as delineated by the Waardenburg Consortium criteria, including dystopia canthorum. The distance between the inner canthi, pupils, and outer canthi calculates a W index for the diagnosis of lateral displacement of the inner canthi. A W index of more than 1.95 shows dystopia. Dystopia canthorum may be difficult to characterize in babies but is the most penetrant sign.
Differential diagnosis
Differential diagnosis includes Waardenburg syndrome type 2, 3 and 4, piebaldism, Tietz syndrome, oculocutaneous albinism, Vogt-Koyanagi-Harada disease(see these terms) and other forms of congenital non-progressive sensorineural hearing loss.
Genetic counseling
In the majority of cases, WS1 is transmitted as an autosomal dominant disorder with a large variable inter- and intrafamilial expressivity. Some affected patients present with a de novo mutation.
Management and treatment
Hearing aids to counter hearing loss and effective therapy to improve language, communication, and cognitive skill are recommended. Associated manifestations are treated as appropriate (e.g. cosmetics to manage the pigmentation defects).
Prognosis
With hearing aids, prognosis is good for most WS1 affected individuals.

                            Last update: 
                            October 2015


                            - Expert reviewer(s): 
                            Dr Véronique PINGAULT
Waardenburg syndrome type 2 (ORPHA:895)
An autosomal dominant subtype of Waardenburg syndrome (WS) characterized by varying degrees of deafness and pigmentation anomalies of eyes, hair and skin, but without dystopia canthorum.
Epidemiology
The prevalence of WS2 is unknown; the worldwide prevalence of WS is estimated at around 1/40,000. WS2 is one of the most common types of Waardenburg syndrome.
Clinical description
Clinical manifestations for WS2 resemble those of Waardenburg syndrome type 1 (WS1; see this term). Sensorineural hearing loss (77%) and heterochromia iridum (47%) are the two most important clinical features for WS. In addition, individuals with WS2 lack dystopia canthorum and are usually more frequently affected by hearing loss and heterochromia iridum. In some cases (mutation in SOX10 gene), patients may present associated signs of Kallmann syndrome (anosmia, hypogonadism; see this term) and/or neurological defects (neurological Waardenburg syndrome).
Etiology
WS2 is genetically very heterogeneous and still much of the etiology of WS2 remains elusive. Mutations have been found in MITF (3p14-p13; subtype designated as WS2A), SNAI2 (8q11.21; WS2D), and SOX10 (22q13.1; WS2E) genes. Furthermore WS2 loci have been mapped to chromosome 1p21-p13.3 (subtype designated as WS2B) and to chromosome 8p23 (designated as WS2C). Digenic inheritance of MITF mutation in combination a TYR mutation (and/or the TYRR402Qhypomorphic allele) has been reported in two families with WS2 and ocular albinism.
Diagnostic methods
Diagnosis is determined by the presence of major and minor characteristic clinical features according to the Waardenburg Consortium criteria, as well as by genetic testing.
Differential diagnosis
Differential diagnosis includes Waardenburg syndrome type 1 and 4, piebaldism, Tietz syndrome, oculocutaneous albinism (see these terms) and other forms of congenital non-progressive sensorineural hearing loss.
Genetic counseling
In the majority of cases, WS2 is transmitted as an autosomal dominant disorder with a large variable inter- and intrafamilial expressivity. Some affected patients present with a de novo mutation.
Management and treatment
Hearing aids to counter hearing loss and effective therapy to improve language, communication, and cognitive skill are recommended. Pigmentation defects do not require medical care but cosmetic products are available. Rarely, in case of extended depigmentation, care is taken to protect the skinand eyesfrom the sun.
Prognosis
With hearing aids, prognosis is good for most affected individuals with WS2.

                            Last update: 
                            October 2015


                            - Expert reviewer(s): 
                            Dr Véronique PINGAULT
Waardenburg syndrome type 3 (ORPHA:896)
A very rare subtype of Waardenburg syndrome (WS) that is characterized by limb anomalies in association with congenital hearing loss, minor defects in structures arising from neural crest, resulting in pigmentation anomalies of eyes, hair, and skin.
Epidemiology
Incidence is unknown, but WS3 is the rarest form of all Waardenburg syndrome types.
Clinical description
WS3 is characterized by the association of limb anomalies (predominantly involving upper limbs, with hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, syndactylia) with features of Waardenburg syndrome (see this term), which include congenital sensorineural hearing loss, hypopigmentation abnormalities of irides, hair and skin and minor facial dysmorphism in combination with dystopia canthorum.
Etiology
WS3 is caused by heterozygous or homozygous mutations in the PAX3 (2q36.1) gene.
Diagnostic methods
Diagnosis is made through criteria of the association of WS1 manifestations with limb anomalies. PAX3 gene analysis confirms diagnosis resulting in an abnormality of melanocytes of skin, ears and hair.
Antenatal diagnosis
Antenatal diagnosis is possible for affected parents.
Genetic counseling
The defects are more severe in homozygous than heterozygous forms. Genetic counseling is recommended.
Management and treatment
Hearing aids to counter hearing loss, effective therapy to improve language, communication, and cognitive skill and limbs physiotherapy are recommended. Associated manifestations are treated as appropriate (e.g. skin and eyes protection from the sun).
Prognosis
Due to the very few number of cases described so far, information on prognosis and quality of life is limited. Disease progression is variable, with symptoms being more severe in homozygous than in heterozygous forms.

                            Last update: 
                            October 2015


                            - Expert reviewer(s): 
                            Dr Véronique PINGAULT
Waardenburg syndrome (ORPHA:3440)
Waardenburg syndrome (WS) is a disorder characterized by varying degrees of deafness and minor defects in structures arising from neural crest, including pigmentation anomalies of eyes, hair, and skin. WS is classified into four clinical and genetic phenotypes.
Epidemiology
The worldwide incidence is estimated at around 1/40,000. Waardenburg syndrome type 1 (WS1) and type 2 (WS2) are the most common types of Waardenburg syndrome. Waardenburg syndrome type3 (WS3) and type 4 (WS4; see these terms) are rarer, with only a few cases of WS3 described worldwide so far. WS accounts for about 3% of all institutionalized cases of congenital hearing loss.
Clinical description
Clinical manifestations vary within and between families. Frequent clinical manifestations include congenital sensorineural deafness, heterochromic or hypoplastic blue irides, white forelock or early graying of the scalp hair before the age of 30 years. All these manifestations, along with a suggestive family history are major criteria, as is dystopia canthorum in WS1 and WS3. Minor criteria include congenital leukoderma, synophrys/medial eyebrow flare, broad/high nasal root with prominent columella and hypoplastic alae nasi. WS is defined by the association of at least 2 major, or 1 major and at least 2 minor clinical criteria (early graying of the hair is considered either a major or minor criteria depending of the WS type). WS1 combines these criteria with dystopia canthorum. The absence of dystopia canthorum clinically differentiates WS2 from WS1, whereas WS3 is similar to WS1, but additionally includes upper limb abnormalities. WS4 is characterized as WS2 with added characteristics of Hirschsprung disease.
Etiology
WS is genetically heterogeneous. To date, mutations in 6 different genes have been identified: PAX3 (2q36.1), MITF (3p14-p13), SNAI2 (8q11.21), SOX10 (22q13.1), EDNRB (13q22.3), and EDN3 (20q13.32). Mutations in PAX3 gene are associated with WS1 and WS3, while MITF gene is mutated in cases of WS2. Digenic inheritance of MITF mutation in combination with a TYR mutation (and/or the TYRR402Q hypomorphic allele) has been reported in two families with WS2 and ocular albinism (see this term). Homozygous SNAI2 deletions have been described in two WS2 patients. SOX10 mutations are found in WS4 and WS2 affected patients. Mutations in EDNRB and EDN3 genes have also been reported in WS4.

                            Last update: 
                            November 2015


                            - Expert reviewer(s): 
                            Dr Véronique PINGAULT
WAC-related facial dysmorphism-developmental delay-behavioral abnormalities syndrome (ORPHA:466943)
A rare, genetic, syndromic intellectual disability characterised by several dysmorphic features, hypotonia, developmental delay, intellectual disability, behavioral problems, visual and hearing abnormalities, constipation, and feeding difficulties. Common dysmorphic features include coarse facies, broad forehead, synophrys, bushy eyebrows, deep-set eyes, downslanting palpebral fissures, epicanthus, depressed nasal bridge, bulbous nasal tip, posteriorly rotated ears, full cheeks, thin upper lip, inverted nipples, and hirsutism. Behavioral problems tend to be dominated by ADHD, but anxiety, aggressive outbursts and autistic features may also present.