{"orpha":488333,"name":"Autosomal dominant Charcot-Marie-Tooth disease type 2W","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Autosomal dominant Charcot-Marie-Tooth disease type 2 due to HARS mutation","CMT2W"],"definition":"A rare predominantly axonal hereditary motor and sensory neuropathy characterized by a broad phenotypic spectrum of slowly progressive signs and symptoms mainly affecting the lower limbs. Most patients present with gait difficulties and distal sensory impairment, while some may lack sensory symptoms altogether. Pes cavus is frequently reported. Age of onset is also highly variable, ranging from childhood to late adulthood.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-488333/","orphanet_url":"https://www.orpha.net/en/disease/detail/488333","names":{"fr":{"name":"Maladie de Charcot-Marie-Tooth autosomique dominante type 2W","synonyms":["CMT2W","Maladie de Charcot-Marie-Tooth autosomique dominante type 2 due à une mutation de HARS"],"definition":"Neuropathie sensitivo-motrice héréditaire rare à prédominance axonale, caractérisée par un large spectre phénotypique de signes et de symptômes à progression lente affectant principalement les membres inférieurs. La plupart des patients présentent des difficultés à la marche et des troubles sensoriels distaux, tandis que certains peuvent être totalement dépourvus de symptômes sensoriels. Des pieds creux sont fréquemment rapportés. L'âge d'apparition est également très variable, allant de l'enfance à la fin de l'âge adulte."},"de":{"name":"Charcot-Marie-Tooth-Krankheit, autosomal-dominante, Typ 2W","synonyms":["CMT2W","Charcot-Marie-Tooth-Krankheit, autosomal-dominante, Typ 2 durch HARS-Genmutation"],"definition":"Eine seltene, vorwiegend axonale Form der hereditären motorischen und sensorischen Neuropathie, die durch ein breites phänotypisches Spektrum langsam fortschreitender Anzeichen und Symptome gekennzeichnet ist, die hauptsächlich die unteren Gliedmaßen betreffen. Die meisten Patienten weisen Gangstörungen und distale sensorische Beeinträchtigungen auf, einige haben jedoch überhaupt keine sensorischen Symptome. Ein Pes cavus wird häufig berichtet. Auch das Alter, in dem die Krankheit auftritt, ist sehr unterschiedlich und reicht von der Kindheit bis zum späten Erwachsenenalter."},"es":{"name":"Enfermedad de Charcot-Marie-Tooth autosómica dominante tipo 2W","synonyms":["CMT2W","Enfermedad de Charcot-Marie-Tooth autosómica dominante tipo 2 por una mutación en el gen HARS"],"definition":"Es una neuropatía predominantemente axonal sensitivo-motora hereditaria y poco frecuente que se caracteriza por un amplio espectro fenotípico de signos y síntomas de progresión lenta que afectan principalmente a las extremidades inferiores. La mayoría de los pacientes presenta dificultades para caminar y afectación sensitiva distal, mientras que algunas personas pueden carecer de síntomas sensitivos por completo. Con frecuencia se describe pie cavo. La edad de aparición también es muy variable, desde la niñez hasta la edad adulta tardía."},"it":{"name":"Malattia di Charcot-Marie-Tooth autosomica dominante tipo 2W","definition":"Si tratta di una neuropatia sensitivo-motoria ereditaria rara, prevalentemente assonale, caratterizzata da un ampio quadro clinico, che comprende sintomi a progressione lenta, che interessano per lo più gli arti inferiori. La maggior parte dei pazienti presenta anomalie dell'andatura e deficit sensoriale distale, mentre alcuni non presentano alcun sintomo sensoriale. Spesso si associa al piede cavo. L'età d'esordio è molto variabile, tra l'infanzia e la tarda età adulta."},"nl":{"name":"Autosomaal dominante ziekte van Charcot-Marie-Tooth type 2W","synonyms":["Autosomaal dominante ziekte van Charcot-Marie-Tooth type 2 als gevolg van een HARS-mutatie","CMT2W"],"definition":"Een zeldzame, hoofdzakelijk axonale hereditaire motorische en sensorische neuropathie, gekarakteriseerd door een breed fenotypisch spectrum van traag progressieve tekenen en symptomen, en met aantasting van vooral onderste ledematen. De meeste patiënten presenteren zich met gangstoornissen en distale sensorische beperking, terwijl bij sommige patiënten sensorische symptomen volledig afwezig zijn. Pes cavus wordt vaak gerapporteerd De aanvangsleeftijd is ook zeer variabel, gaande van de kindertijd tot de late volwassenheid."},"pt":{"name":"Doença de Charcot-Marie-Tooth autossómica dominante tipo 2W"},"pl":{"name":"Autosomalna dominująca choroba Charcota, Mariego i Tootha typu 2W","synonyms":["Autosomalna dominująca choroba Charcota, Mariego i Tootha typu 2 z powodu mutacji w HARS"]},"cs":{"name":"Autozomálně dominantní Charcot-Marie-Toothova nemoc, typ 2W","synonyms":["CMT2W","Autozomálně dominantní Charcot-Marie-Toothova nemoc, typ 2W podmíněná mutací HARS genu"]},"uk":{"name":"Аутосомно-домінантна хвороба Шарко-Марі-Тута, тип 2W","synonyms":["Аутосомно-домінантна хвороба Шарко-Марі-Тута 2 типу, зумовлена мутацією HARS","CMT2W"],"definition":"A rare predominantly axonal hereditary motor and sensory neuropathy characterized by a broad phenotypic spectrum of slowly progressive signs and symptoms mainly affecting the lower limbs. Most patients present with gait difficulties and distal sensory impairment, while some may lack sensory symptoms altogether. Pes cavus is frequently reported. Age of onset is also highly variable, ranging from childhood to late adulthood."},"zh":{"name":"常染色体显性Charcot-Marie-Tooth病2W型","synonyms":["HARS突变导致的常染色体显性夏洛特-玛丽齿病2型"],"definition":"一种罕见的以轴突为主的遗传性运动和感觉神经病，其特征是广泛的表型谱，主要影响下肢缓慢进展的症状和体征。大多数患者表现为步态困难和远端感觉障碍，但有些患者可能完全没有感觉症状。高弓足也常有。发病年龄也有很大差异，从儿童到成年晚期都有。"},"tr":{"name":"Otozomal dominant Charcot-Marie-Tooth hastalığı tip 2W","synonyms":["CMT2W","HARS mutasyonuna bağlı otozomal baskın Charcot-Marie-Tooth hastalığı tip 2"]}},"xrefs":[{"source":"OMIM","code":"616625","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G60.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014711","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5567486","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":64746,"name":"Autosomal dominant Charcot-Marie-Tooth disease type 2","classifications":[156,181]}],"children":[],"genes":[{"symbol":"HARS1","name":"histidyl-tRNA synthetase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26072516[PMID]","hgnc":"4816","ensembl":"ENSG00000170445","omim":"142810","loci":["5q31.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Adolescent","Adult","Childhood"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":24.0,"area":"Worldwide","status":"Validated","source":"26072516[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26072516[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-03-01","source":"26072516[PMID]","terms":[{"hpo":"HP:0007108","label":"Demyelinating peripheral neuropathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0009053","label":"Distal lower limb muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008959","label":"Distal upper limb muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002166","label":"Impaired vibration sensation in the lower limbs","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003474","label":"Somatic sensory dysfunction","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001760","label":"Abnormal foot morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001348","label":"Brisk reflexes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007002","label":"Motor axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003376","label":"Steppage gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003438","label":"Absent Achilles reflex","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001765","label":"Hammertoe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030237","label":"Hand muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006937","label":"Impaired distal tactile sensation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007328","label":"Impaired pain sensation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008954","label":"Intrinsic hand muscle atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012531","label":"Pain","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003100","label":"Slender long bone","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Occasional (29-5%)","criteria":null}]}}