{"orpha":90658,"name":"Charcot-Marie-Tooth disease type 1E","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CMT1E","Charcot-Marie-Tooth disease-deafness syndrome","Charcot-Marie-Tooth disease-hearing loss syndrome"],"definition":"A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the <i>PMP22</i> (17p12) gene. The disease severity depends on the particular <i>PMP22</i> mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-90658/","orphanet_url":"https://www.orpha.net/en/disease/detail/90658","names":{"fr":{"name":"Maladie de Charcot-Marie-Tooth type 1E","synonyms":["CMT1E","Syndrome de maladie de Charcot-Marie-Tooth-surdité"],"definition":"Sous-type rare de maladie de Charcot-Marie-Tooth type&nbsp;1 (CMT1), caractérisé par un tableau clinique variable. La maladie débute souvent au cours des deux premières années de vie par un retard de la marche, mais peut aussi se manifester plus tard. Elle est causée par des mutations ponctuelles du gène <i>PMP22</i> (17p12). La sévérité de la maladie dépend du type de mutation du gène <i>PMP22</i>, certains cas étant très légers, ressemblant même à une neuropathie héréditaire avec tendance aux paralysies de pression, tandis que d'autres se manifestent plus tôt et sont associés à un phénotype plus sévère (faisant penser au syndrome de Dejerine-Sottas) que celui observé dans la CMT1A, causée par une duplication du gène. Dans les cas sévères, une surdité et un ralentissement de la vitesse de conduction des nerfs moteurs, beaucoup plus important que chez les patients atteints de CMT1A, peuvent être associés."},"de":{"name":"Charcot-Marie-Tooth-Krankheit Typ 1E","synonyms":["CMT1E","Charcot-Marie-Tooth-Krankheit - Schwerhörigkeit"],"definition":"Die Charcot-Marie-Tooth-Erkrankung Typ 1E (CMT1E) ist ein seltener Subtyp der CMT1 (siehe dort), die sich klinisch variabel präsentieren kann. Nicht selten beginnt die Erkrankung in den ersten beiden Lebensjahren mit verzögertem Beginn des Laufens; dennoch kann sie sich auch erst später manifestieren. CMT1E wird durch Punktmutationen im <i>PMP22</i>-Gen (17p12) verursacht. Die Schwere der Erkrankung ist abhängig von der entsprechenden <i>PMP22</i>-Mutation und variiert von milden Verläufen, die auch der Hereditären Neuropathie mit Neigung zu Drucklähmungen (siehe dort) ähneln können, bis hin zu schwereren, durch Gen-Duplikationen hervorgerufenen, früher beginnenden Verläufen als bei der CMT1A (die an das Dejerine-Sottas-Syndrom erinnern, siehe dort). Bei diesen schweren Verläufen können auch Schwerhörigkeit und deutlich verlangsamte Nervenleitgeschwindigkeiten im Vergleich zu CMT1A-Patienten auftreten."},"es":{"name":"Enfermedad de Charcot-Marie-Tooth tipo 1E","synonyms":["CMT1E","Síndrome de enfermedad de Charcot-Marie-Tooth-hipoacusia","Síndrome de enfermedad de Charcot-Marie-Tooth-sordera"],"definition":"Esta entidad representa un subtipo poco frecuente de CMT1 caracterizado por una presentación clínica variable. La aparición precoz en los dos primeros años de vida asociada a retraso de la marcha no es inusual; sin embargo, puede debutar más tarde. La enfermedad está causada por mutaciones puntuales en el gen <i>PMP22</i> (17p12). La gravedad de la enfermedad depende de la mutación particular en <i>PMP22</i>, dándose algunos casos muy leves que se asemejan incluso a una neuropatía hereditaria con susceptibilidad a la parálisis por presión, mientras que otros tienen un inicio temprano con un fenotipo más grave (reminiscente del síndrome de Dejerine-Sottas) que el que se observa en la CMT1A causado por una duplicación del gen <i>PMP22</i>. Estos casos graves también pueden manifestar sordera y una velocidad de conducción nerviosa motora mucho más lenta en comparación con los pacientes clásicos con la CMT1A."},"it":{"name":"Malattia di Charcot-Marie-Tooth, tipo 1E","synonyms":["CMT1E","Malattia di Charcot-Marie-Tooth - sordità"],"definition":"La malattia di Charcot-Marie-Tooth tipo 1E (CMT1E) è un sottotipo raro della CMT1 (si veda questo termine). E' caratterizzata da un quadro clinico variabile. Spesso la malattia esordisce nei primi due anni di vita con ritardo nella deambulazione, ma può manifestarsi anche successivamente. La CMT1E è causata dalle mutazioni puntiformi nel gene <i> PMP22 </i> (17p12). La gravità della malattia dipende dal tipo di mutazione presente in <i>PMP22</i>: alcuni casi hanno un decorso clinico molto lieve che può ricordare la neuropatia ereditaria con suscettibilità alle paralisi da pressione, mentre altri hanno un esordio più precoce e si associano ad un fenotipo più grave (che ricorda la sindrome di Dejerine-Sottas; si vedano questi termini) rispetto a quello della CMT1A, da duplicazione del gene. Nei casi gravi può associarsi la sordità e un rallentamento della velocità di conduzione dei nervi motori, che è molto più importante rispetto a quella dei pazienti con CMT1A."},"nl":{"name":"Ziekte van Charcot-Marie-Tooth type 1E","synonyms":["CMT1E","Ziekte van Charcot-Marie-Tooth - doofheid-syndroom"],"definition":"Een zeldzaam subtype van CMT1 gekarakteriseerd door een variabele klinische presentatie. Aanvang binnen de eerste twee levensjaren met een loopachterstand is niet uitzonderlijk, hoewel de ziekte ook later kan aanvangen. CMT1E wordt veroorzaakt door puntmutaties in het gen <i>PMP22</i> (17p12). De ernst van de ziekte hangt af van de specifieke mutatie in <i>PMP22</i>, waarbij sommige gevallen zeer mild zijn en zelfs lijken op erfelijke neuropathie met vatbaarheid voor drukverlammingen, terwijl anderen een vroegere aanvang vertonen met een ernstiger fenotype (dat doet denken aan syndroom van Dejerine-Sottas) dan dat van CMT1A, veroorzaakt door genduplicatie. Mogelijk vertonen deze ernstige gevallen ook doofheid en veel tragere motorische zenuwgeleidingssnelheden in vergelijking met CMT1A-patiënten."},"pt":{"name":"Doença de Charcot-Marie-Tooth tipo 1E"},"pl":{"name":"Choroba Charcota, Mariego i Tootha typu 1E","synonyms":["Choroba Charcota, Mariego i Tootha - głuchota","CMT1E"]},"cs":{"name":"Charcotova-Marieova-Toothova nemoc, typ 1E","synonyms":["CMT1E","Charcotova-Marieova-Toothova nemoc a hluchota","Charcot-Marie-Toothova nemoc, typ 1E","Charcot-Marie-Toothova nemoc a hluchota"]},"uk":{"name":"Хвороба Шарко-Марі-Тута, тип 1Е","synonyms":["Синдром глухоти при хворобі Шарко-Марі-Тута","Хвороба Шарко-Марі-Тута - синдром втрати слуху","ШМТ1E"],"definition":"A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the <i>PMP22</i> (17p12) gene. The disease severity depends on the particular <i>PMP22</i> mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients."},"zh":{"name":"腓骨肌萎缩症1E型","synonyms":["腓骨肌萎缩症-听觉丧失综合征"]},"tr":{"name":"Charcot-Marie-Tooth hastalığı tip 1E","synonyms":["CMT1E","Charcot-Marie-Tooth hastalığı-sağırlık sendromu","Charcot-Marie-Tooth hastalığı-işitme kaybı sendromu"]}},"xrefs":[{"source":"OMIM","code":"118300","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":"1924906594"},{"source":"MONDO","code":"0007311","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537986","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2931686","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"9190","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":65753,"name":"Charcot-Marie-Tooth disease type 1","classifications":[156,181]},{"orpha":90642,"name":"Rare syndromic genetic deafness","classifications":[147,156,200]}],"children":[],"genes":[{"symbol":"PMP22","name":"peripheral myelin protein 22","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301384[PMID]","hgnc":"9118","ensembl":"ENSG00000109099","omim":"601097","loci":["17p12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_23224996[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-02-11","source":"27774063[PMID]_11920834[PMID]","terms":[{"hpo":"HP:0000762","label":"Decreased nerve conduction velocity","frequency":"Very frequent (99-80%)","criteria":null},{"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:0002936","label":"Distal sensory impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000615","label":"Abnormal pupil morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010832","label":"Abnormality of pain sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031006","label":"Acroparesthesia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002522","label":"Areflexia of lower limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008962","label":"Calf muscle hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008944","label":"Distal lower limb amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009027","label":"Foot dorsiflexor weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009130","label":"Hand muscle atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030237","label":"Hand muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002600","label":"Hyporeflexia of lower limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012391","label":"Hyporeflexia of upper limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010830","label":"Impaired tactile sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010829","label":"Impaired temperature sensition","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002166","label":"Impaired vibration sensation in the lower limbs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009049","label":"Peroneal muscle atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011727","label":"Peroneal muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002172","label":"Postural instability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030211","label":"Slow pupillary light response","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012074","label":"Tonic pupil","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009916","label":"Anisocoria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012735","label":"Cough","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008110","label":"Equinovarus deformity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002141","label":"Gait imbalance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001765","label":"Hammertoe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009473","label":"Joint contracture of the hand","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011476","label":"Profound sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001171","label":"Split hand","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003376","label":"Steppage gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008124","label":"Talipes calcaneovarus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000360","label":"Tinnitus","frequency":"Occasional (29-5%)","criteria":null}]}}