{"orpha":466934,"name":"VPS11-related autosomal recessive hypomyelinating leukodystrophy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["VPS11-related autosomal recessive hypomyelinating leukoencephalopathy"],"definition":"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.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-466934/","orphanet_url":"https://www.orpha.net/en/disease/detail/466934","names":{"fr":{"name":"Leucodystrophie hypomyélinisante autosomique récessive associée à VPS11","synonyms":["Leucoencéphalopathie hypomyélinisante autosomique récessive associée à VPS11"],"definition":"Leucodystrophie génétique rare identifiée dans des familles d'origine juive ashkénaze, caractérisée par l'apparition, dès la petite enfance, d'un retard de développement global sévère et par un langage très limité, voire absent, et parfois une absence totale de développement moteur, une hypotonie, une spasticité et une microcéphalie acquise. Des crises d'épilepsie, une perte auditive, une déficience visuelle et une dysautonomie ont également été décrites. L'imagerie cérébrale met en évidence un retard de myélinisation et d'autres anomalies de la substance blanche."},"de":{"name":"Hypomyelinisierende Leukodystrophie, VPS11-abhängige, autosomal-rezessive","synonyms":["VPS11-assoziierte autosomal-rezessive hypomyelinisierende Leukodystrophie"],"definition":"Eine genetisch bedingte Leukodystrophie, die in Familien aschkenasischer jüdischer Abstammung auftritt und durch eine im Säuglingsalter einsetzende schwere globale Entwicklungsverzögerung mit sehr eingeschränkter oder fehlender Sprache und manchmal völlig fehlender motorischer Entwicklung, Hypotonie, Spastizität und erworbener Mikrozephalie gekennzeichnet ist. Krampfanfälle, Hörverlust, Sehstörungen und autonome Funktionsstörungen wurden ebenfalls beschrieben. Die Bildgebung des Gehirns zeigt eine verzögerte Myelinisierung und andere Anomalien der weißen Substanz."},"es":{"name":"Leucodistrofia hipomielinizante autosómica recesiva asociada a VPS11","synonyms":["Leucoencefalopatía hipomielinizante autosómica recesiva asociada a VPS11"],"definition":"Es una leucodistrofia genética poco frecuente identificada en familias de ascendencia judía asquenazí, caracterizada por el inicio en la infancia de un retraso global grave del desarrollo psicomotor con ausencia o limitaciones del habla y, ocasionalmente, ausencia completa del desarrollo motor, hipotonía, espasticidad y microcefalia adquirida. También se han descrito crisis, hipoacusia, discapacidad visual y disfunción autonómica. Las imágenes cerebrales muestran un retraso de la mielinización y otras anomalías de la sustancia blanca."},"it":{"name":"Leucodistrofia ipomielinizzante autosomica recessiva correlata a VPS11","definition":"Si tratta di una leucodistrofia genetica rara, diagnosticata in alcune famiglie di origine ebrea askenazita, caratterizzata da grave ritardo dello sviluppo globale ad esordio infantile, associato ad un linguaggio molto limitato o del tutto assente e, occasionalmente, all'assenza dello sviluppo motorio, all'ipotonia, alla spasticità e alla microcefalia acquisita. I pazienti possono presentare anche crisi epilettiche, sordità, deficit visivi e disfunzione del sistema autonomo. Le neuroimmagini mostrano ritardo della mielinizzazione e altre anomalie della sostanza bianca."},"nl":{"name":"VPS11-gerelateerde autosomaal recessieve hypomyeliniserende leukodystrofie","synonyms":["VPS11-gerelateerde autosomaal recessieve hypomyeliniserende leuko-encefalopathie"],"definition":"Een zeldzame, genetische leukodystrofie, geïdentificeerd in families van Asjkenazisch Joodse afkomst, en gekarakteriseerd door aanvang in de zuigelingentijd van ernstige algehele ontwikkelingsachterstand met zeer beperkte of afwezige spraak en soms volledige afwezigheid van motorische ontwikkeling, hypotonie, spasticiteit, en verworven microcefalie. Insulten, gehoorverlies, verlies van gezichtsvermogen, en autonome disfunctie werden ook reeds beschreven. Beeldvorming van hersenen toont vertraagde myelinisatie en andere afwijkingen van witte stof."},"pt":{"name":"Leucodistrofia hipomelizante autossómica recessiva VPS11-relacionada"},"pl":{"name":"Autosomalna recesywna leukodystrofia hipomielinizacyjna zależna od VPS11","synonyms":["Autosomalna recesywna leukoencefalopatia hipomielinizacyjna zależna od VPS11"]},"cs":{"name":"VPS11 asociovaná autozomálně recesivní hypomyelinizační leukodystrofie","synonyms":["VPS11-related autosomal recessive hypomyelinating leukoencephalopathy","Autozomálně recesivní hypomyelinizační leukoencefalopatie související s VPS11"]},"uk":{"name":"Автосомно-рецесивна гіпомієлінізуюча лейкодистрофія, повязана з VPS11","synonyms":["Аутосомно-рецесивна гіпомієлінізуюча лейкоенцефалопатія, повязана з VPS11"],"definition":"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."},"zh":{"name":"VPS11相关常染色体隐性遗传性脑白质营养不良-髓鞘发育不良病","synonyms":["VPS11相关常染色体隐性脑白质营养不良-髓鞘发育不良病"],"definition":"在德系犹太人血统家族中发现的一种罕见的遗传性脑白质营养不良，其特征是婴儿期开始出现严重的全面发育迟缓，语言能力非常有限或缺失，有时完全没有运动发育，肌张力低下，痉挛和后天性小脑萎缩。也有癫痫发作、听力损失、视觉障碍和自主神经功能障碍。脑成像显示髓鞘发育迟缓和其他白质异常。"},"tr":{"name":"VPS11-ilişkili otozomal resesif hipomiyelinizan lökodistrofi","synonyms":["VPS11-ilişkili otozomal çekinik hipomiyelinizan lökoensefalopati"]}},"xrefs":[{"source":"OMIM","code":"616683","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G93.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014732","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5568878","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":68356,"name":"Leukodystrophy","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"VPS11","name":"VPS11 core subunit of CORVET and HOPS complexes","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26307567[PMID]","hgnc":"14583","ensembl":"ENSG00000160695","omim":"608549","loci":["11q23.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":13.0,"area":"Worldwide","status":"Validated","source":"26307567[PMID]_27119754[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26307567[PMID]_27119754[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-03-05","source":"26307567[PMID]_27120463[PMID]","terms":[{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012332","label":"Abnormal autonomic nervous system physiology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002019","label":"Constipation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002188","label":"Delayed CNS myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007204","label":"Diffuse white matter abnormalities","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002373","label":"Febrile seizure (within the age range of 3 months to 6 years)","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002828","label":"Multiple joint contractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000011","label":"Neurogenic bladder","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007301","label":"Oromotor apraxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Excluded (0%)","criteria":null},{"hpo":"HP:0001433","label":"Hepatosplenomegaly","frequency":"Excluded (0%)","criteria":null}]}}