{"orpha":99948,"name":"Charcot-Marie-Tooth disease type 4A","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CMT4A"],"definition":"A form of Charcot-Marie-Tooth disease type 4 characterized by early-onset (infancy to early childhood) of severe, rapidly progressing axonal, demyelinating, or intermediate sensorimotor neuropathy usually affecting first, and more severely, the distal lower extremities and later the proximal muscles and upper extremities. Nerve conduction velocities range from very slow to normal. Apart from the typical CMT phenotype (distal muscle weakness and atrophy, sensory loss, frequent pes cavus foot deformity), patients commonly present delayed motor development, vocal cord paresis, mild sensory loss, abolished deep tendon reflexes, and skeletal deformities.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-99948/","orphanet_url":"https://www.orpha.net/en/disease/detail/99948","names":{"fr":{"name":"Maladie de Charcot-Marie-Tooth type 4A","synonyms":["CMT4A"],"definition":"Forme de la maladie de Charcot-Marie-Tooth type 4, caractérisée par une apparition précoce (de la petite enfance au début de l'enfance) d'une neuropathie sensitivo-motrice d'évolution rapide, de type axonal, démyélinisante ou intermédiaire, touchant généralement en premier lieu, et de manière plus prononcée, les extrémités distales des membres inférieurs, puis les muscles proximaux et les membres supérieurs. Les vitesses de conduction nerveuses varient de très lentes à normales. En dehors du phénotype typique de la CMT (faiblesse et atrophie musculaires distales, perte sensorielle, pieds creux retrouvés fréquemment), les patients présentent souvent un retard de développement moteur, une parésie des cordes vocales, une légère perte sensorielle, une abolition des réflexes tendineux profonds et des déformations squelettiques."},"de":{"name":"Charcot-Marie-Tooth-Krankheit Typ 4A","synonyms":["CMT4A"],"definition":"Ein Subtyp der Charcot-Marie-Tooth-Krankheit Typ 4, der durch ein frühes Auftreten (Säuglingsalter bis frühe Kindheit) einer schweren, schnell fortschreitenden demyelinisierenden, axonalen oder intermediären sensomotorischen Neuropathie gekennzeichnet ist, die in der Regel zuerst und in stärkerem Maße die distalen unteren Extremitäten und später die proximalen Muskeln und oberen Extremitäten betrifft. Die Nervenleitgeschwindigkeiten reichen von sehr langsam bis normal. Neben dem typischen CMT-Phänotyp (distale Muskelschwäche und -atrophie, Sensibilitätsverlust, häufige Pes-cavus-Fußdeformität) zeigen die Patienten häufig eine verzögerte motorische Entwicklung, Stimmbandparese, leichten Sensibilitätsverlust, fehlende tiefe Sehnenreflexe und Skelettdeformitäten."},"es":{"name":"Enfermedad de Charcot-Marie-Tooth tipo 4A","definition":"La enfermedad de Charcot-Marie-Tooth tipo 4A (CMT4A) es un subtipo de la enfermedad de Charcot-Marie-Tooth tipo 4 de inicio temprano (lactancia a la primera infancia) caracterizado por neuropatía sensitivo-motora de tipo axonal, intermedio o desmielinizante grave de progresión rápida que suele afectar en primer lugar y en mayor medida a los músculos distales de las extremidades inferiores y después a los músculos proximales y extremidades superiores. Las velocidades de conducción nerviosa van desde muy lentas hasta normales. Aparte del típico fenotipo CMT (debilidad muscular distal y atrofia, pérdida sensorial, deformidad frecuente del pie cavo), los pacientes suelen presentar retraso del desarrollo motor, paresia de las cuerdas vocales, pérdida sensorial leve, ausencia de los reflejos tendinosos profundos y deformidades esqueléticas."},"it":{"name":"Malattia di Charcot-Marie-Tooth, tipo 4A","synonyms":["CMT4A"],"definition":"La malattia di Charcot-Marie-Tooth tipo 4A (CMT4A) è un sottotipo della malattia di Charcot-Marie-Tooth tipo 4; è caratterizzata da neuropatia sensitivo-motoria demielinizzante, assonale o intermedia grave, a progressione rapida ed esordio precoce (nel periodo neonatale o nella prima infanzia), che di solito interessa inizialmente, e in maniera più grave, le porzioni distali degli arti inferiori e, successivamente, i muscoli prossimali e gli arti superiori. La velocità di conduzione dei nervi può essere molto lenta o normale. Oltre al quadro clinico tipico della malattia di Charcot-Marie-Tooth (debolezza e atrofia dei muscoli distali, perdita sensoriale, frequente piede cavo), i pazienti presentano ritardo dello sviluppo psicomotorio, paralisi delle corde vocali, perdita sensoriale lieve, assenza dei riflessi tendinei profondi e deformità scheletriche."},"nl":{"name":"Ziekte van Charcot-Marie-Tooth type 4A","synonyms":["CMT4A"],"definition":"Ziekte van Charcot-Marie-Tooth type 4A (CMT4A) is een subtype van ziekte van Charcot-Marie-Tooth type 4 dat gekarakteriseerd wordt door vroege aanvang (zuigelingen- tot vroege kindertijd) van ernstige, snel progressieve, demyeliniserende, axonale of intermediaire sensomotorische neuropathie die meestal eerst, en in ergere mate, de distale onderste ledematen treft, en later de proximale spieren en bovenste ledematen. Zenuwgeleidingssnelheden gaan van zeer traag tot normaal. Naast het typische CMT-fenotype (distale spierzwakte en -atrofie, zintuigelijk verlies, frequente pes cavus (holvoet)), vertonen patiënten doorgaans motorische ontwikkelingsachterstand, stembandverlamming, mild zintuigelijk verlies, afwezige diepe peesreflexen, en skeletmisvormingen."},"pt":{"name":"Doença de Charcot-Marie-Tooth tipo 4A","definition":"A doença de Charcot-Marie-Tooth, tipo 4A (CMT4A) é uma forma grave e de apresentação precoce de polineuropatia sensitivomotora periférica de CMT do tipo desmielinizante caracterizada por atraso motor grave e escoliose progressiva."},"pl":{"name":"Choroba Charcota, Mariego i Tootha typu 4A","synonyms":["CMT4A"]},"cs":{"name":"Charcotova-Marieova-Toothova nemoc, typ 4A","synonyms":["CMT4A","Charcot-Marie-Toothova nemoc, typ 4A"]},"uk":{"name":"Хвороба Шарко-Марі-Тута, тип 4А","synonyms":["CMT4A"],"definition":"Charcot-Marie-Tooth disease type 4A (CMT4A) is a subtype of Charcot-Marie-Tooth disease type 4 characterized by early-onset (infancy to early childhood) of severe, rapidly progressing demyelinating, axonal, or intermediate sensorimotor neuropathy usually affecting first, and more severely, the distal lower extremities and later the proximal muscles and upper extremities. Nerve conduction velocities range from very slow to normal. Apart from the typical CMT phenotype (distal muscle weakness and atrophy, sensory loss, frequent pes cavus foot deformity), patients commonly present delayed motor development, vocal cord paresis, mild sensory loss, abolished deep tendon reflexes, and skeletal deformities."},"zh":{"name":"腓骨肌萎缩症4A型","synonyms":["CMT4A"],"definition":"Charcot-Marie-Tooth病4A型(CMT4A)是Charcot-Marie-Tooth病4型的一个亚型，其特征是早期(婴儿期至儿童期)出现严重的、进展迅速的脱髓鞘性轴索性或中度感觉运动性神经病，通常首先影响下肢远端，然后是近端肌肉和上肢。神经传导速度从非常慢到正常不等。除了典型的CMT表型(远端肌肉无力和萎缩，感觉丧失，经常出现下腔静脉足畸形)外，患者通常表现为运动发育延迟，声带瘫痪，轻度感觉丧失，深肌腱反射消失和骨骼畸形。"},"tr":{"name":"Charcot-Marie-Tooth hastalığı tip 4A","synonyms":["CMT4A"]}},"xrefs":[{"source":"OMIM","code":"214400","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G60.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8C20.0","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1476665103"},{"source":"MONDO","code":"0008961","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C535419","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1859198","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":64749,"name":"Charcot-Marie-Tooth disease type 4","classifications":[156,181]}],"children":[],"genes":[{"symbol":"GDAP1","name":"ganglioside induced differentiation associated protein 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301711[PMID]","hgnc":"15968","ensembl":"ENSG00000104381","omim":"606598","loci":["8q21.11"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Not yet validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-10-28","source":"26848201[PMID]_20301711[PMID]","terms":[{"hpo":"HP:0001760","label":"Abnormal foot morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000762","label":"Decreased nerve conduction velocity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003693","label":"Distal amyotrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002460","label":"Distal muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002936","label":"Distal sensory impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003457","label":"EMG abnormality","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007010","label":"Poor fine motor coordination","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007015","label":"Poor gross motor coordination","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001284","label":"Areflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001776","label":"Bilateral talipes equinovarus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007267","label":"Chronic axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009072","label":"Decreased Achilles reflex","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003387","label":"Decreased number of large peripheral myelinated nerve fibers","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001765","label":"Hammertoe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030237","label":"Hand muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001609","label":"Hoarse voice","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012391","label":"Hyporeflexia of upper limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006858","label":"Impaired distal proprioception","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006937","label":"Impaired distal tactile sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006886","label":"Impaired distal vibration sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007328","label":"Impaired pain sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009473","label":"Joint contracture of the hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006064","label":"Limited interphalangeal movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006248","label":"Limited wrist movement","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002317","label":"Unsteady gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001604","label":"Vocal cord paresis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007108","label":"Demyelinating peripheral neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009109","label":"Denervation of the diaphragm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002359","label":"Frequent falls","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008935","label":"Generalized neonatal hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012078","label":"Motor conduction block","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003731","label":"Quadriceps muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002091","label":"Restrictive ventilatory defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003547","label":"Shoulder girdle muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008443","label":"Spinal deformities","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030319","label":"Weakness of facial musculature","frequency":"Very rare (<4-1%)","criteria":null}]}}