{"orpha":466768,"name":"Autosomal dominant Charcot-Marie-Tooth disease type 2Z","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Autosomal dominant Charcot-Marie-Tooth disease type 2 due to MORC2 mutation","CMT2Z"],"definition":"A rare autosomal dominant hereditary axonal motor and sensory neuropathy characterized by early onset of generalized hypotonia and weakness, or later onset of distal lower limb muscle weakness and atrophy, cramps, and sensory impairment. Weakness and atrophy progress in an asymmetric fashion to involve also the proximal and upper limbs in the course of the disease. Additional features are pyramidal signs like increased muscle tone and extensor plantar reflexes, as well as learning difficulties.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-466768/","orphanet_url":"https://www.orpha.net/en/disease/detail/466768","names":{"fr":{"name":"Maladie de Charcot-Marie-Tooth autosomique dominante type 2Z","synonyms":["CMT2Z","Maladie de Charcot-Marie-Tooth autosomique dominante type 2 due à une mutation de MORC2"],"definition":"Neuropathie sensitivo-motrice axonale héréditaire autosomique dominante rare caractérisée par l'apparition précoce d'une hypotonie et d'une faiblesse généralisées, ou par l'apparition plus tardive d'une faiblesse et d'une atrophie des muscles distaux des membres inférieurs, des crampes et des troubles sensoriels. La faiblesse et l'atrophie progressent de manière asymétrique et touchent également les muscles proximaux et les membres supérieurs au cours de l'évolution de la maladie. Les autres signes cliniques sont ceux d'une atteinte pyramidale, tels qu'une augmentation du tonus musculaire, des réflexes cutanés plantaires, ainsi que des difficultés d'apprentissage."},"de":{"name":"Charcot-Marie-Tooth-Krankheit, autosomal-dominante, Typ 2Z","synonyms":["CMT2Z","Charcot-Marie-Tooth-Krankheit, autosomal-dominante, Typ 2, durch MORC2-Genmutation"],"definition":"Eine autosomal-dominante motorische-sensorische axonale Neuropathie, die durch ein frühes Auftreten von generalisierter Hypotonie und Schwäche oder ein späteres Auftreten von distaler Muskelschwäche und -atrophie der unteren Gliedmaßen, Krämpfen und sensorischen Störungen gekennzeichnet ist. Schwäche und Atrophie schreiten asymmetrisch voran und betreffen im Verlauf der Krankheit auch die proximalen und oberen Gliedmaßen. Weitere Merkmale sind pyramidale Anzeichen wie erhöhter Muskeltonus und Plantarstreckreflexe sowie Lernschwierigkeiten."},"es":{"name":"Enfermedad de Charcot-Marie-Tooth autosómica dominante tipo 2Z","synonyms":["CMT2Z","Enfermedad de Charcot-Marie-Tooth autosómica dominante tipo 2 por una mutación en el gen MORC2"],"definition":"Es una neuropatía axonal sensitivo-motora hereditaria autosómica dominante poco frecuente caracterizada por un inicio temprano de hipotonía y debilidad generalizadas o por un inicio tardío de debilidad y atrofia muscular distal de las extremidades inferiores, calambres y trastorno sensitivo. La debilidad y la atrofia progresan de forma asimétrica afectando también a la parte proximal de las extremidades superiores durante el curso de la enfermedad. Otros hallazgos adicionales son signos piramidales tales como el aumento del tono muscular y reflejos plantares extensores, así como dificultades de aprendizaje."},"it":{"name":"Malattia di Charcot-Marie-Tooth autosomica dominante tipo 2Z","definition":"Si tratta di una neuropatia sensitivo-motoria assonale ereditaria rara, a trasmissione autosomica dominante, caratterizzata da ipotonia e debolezza generalizzate ad esordio precoce, oppure da debolezza e atrofia dei muscoli distali degli arti inferiori ad esordio più tardivo, crampi e deficit sensoriale. La debolezza e l'atrofia progrediscono in maniera asimmetrica, interessando anche i muscoli prossimali e gli arti superiori. Altri segni clinici sono i sintomi piramidali, come l'aumento del tono muscolare e i riflessi plantari in estensione, e le difficoltà di apprendimento."},"nl":{"name":"Autosomaal dominante ziekte van Charcot-Marie-Tooth type 2Z","synonyms":["Autosomaal dominante ziekte van Charcot-Marie-Tooth type 2 als gevolg van een MORC2-mutatie","CMT2Z"],"definition":"Een zeldzame autosomaal dominante hereditaire axonale motorische en sensorische neuropathie, gekarakteriseerd door vroege aanvang van gegeneraliseerde hypotonie en zwakte, of latere aanvang van spierzwakte en -atrofie, krampen, en sensorische stoornis in distale onderste ledematen. Zwakte en atrofie evolueren asymmetrisch en treffen gedurende het verloop van de ziekte ook proximale en bovenste ledematen. Bijkomende kenmerken zijn piramidale tekenen zoals verhoogde spiertonus en voetzoolreflex met extensie, alsook leermoeilijkheden."},"pt":{"name":"Doença de Charcot-Marie-Tooth autossómica dominante tipo 2Z"},"pl":{"name":"Autosomalna dominująca choroba Charcota, Mariego i Tootha typu 2Z","synonyms":["Autosomalna dominująca choroba Charcota, Mariego i Tootha typu 2 spowodowana mutacją MORC2","CMT2Z"]},"cs":{"name":"Autozomálně dominantní Charcot-Marie-Toothova nemoc, typ 2Z","synonyms":["CMT2Z","Autosomal dominant Charcot-Marie-Tooth disease type 2 due to MORC2 mutation","Autozomálně dominantní Charcot-Marie-Toothova choroba typu 2 způsobená mutací MORC2"]},"uk":{"name":"Аутосомно-домінантна хвороба Шарко-Марі-Тута, тип 2Z","synonyms":["Аутосомно-домінантна хвороба Шарко-Марі-Тута, тип 2, зумовлена мутацією MORC2","CMT2Z"],"definition":"A rare autosomal dominant hereditary axonal motor and sensory neuropathy characterized by early onset of generalized hypotonia and weakness, or later onset of distal lower limb muscle weakness and atrophy, cramps, and sensory impairment. Weakness and atrophy progress in an asymmetric fashion to involve also the proximal and upper limbs in the course of the disease. Additional features are pyramidal signs like increased muscle tone and extensor plantar reflexes, as well as learning difficulties."},"zh":{"name":"常染色体显性Charcot-Marie-Tooth病2Z型","synonyms":["CMT2Z"],"definition":"一种罕见的常染色体显性遗传性轴索运动和感觉神经病，其特点是早期出现全身肌张力低下和无力，或后期出现下肢远端肌肉无力和萎缩、痉挛和感觉障碍。无力和萎缩以不对称的方式进展，在病程中也累及近端和上肢。其他特征是锥体束征，如肌张力增高和跖伸肌反射，以及学习困难。"},"tr":{"name":"Otozomal dominant Charcot-Marie-Tooth hastalığı tip 2Z","synonyms":["MORC2 mutasyonuna bağlı otozomal baskın Charcot-Marie-Tooth hastalığı tip 2","CMT2Z"]}},"xrefs":[{"source":"OMIM","code":"616688","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G60.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014736","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5569025","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":"MORC2","name":"MORC family CW-type zinc finger 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26497905[PMID]","hgnc":"23573","ensembl":"ENSG00000133422","omim":"616661","loci":["22q12.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Adolescent","Adult","Childhood","Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":21.0,"area":"Worldwide","status":"Validated","source":"26497905[PMID]_26659848[PMID]_26912637[PMID]_27105897[PMID]_27329773[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26497905[PMID]_26659848[PMID]_26912637[PMID]_27105897[PMID]_27329773[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-17","source":"26497905[PMID]_26659848[PMID]_30624633[PMID]_28678038[PMID]_28771897[PMID]","terms":[{"hpo":"HP:0100290","label":"Abnormality of peripheral somatosensory evoked potentials","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008944","label":"Distal lower limb amyotrophy","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:0002460","label":"Distal muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007210","label":"Lower limb amyotrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007327","label":"Mixed demyelinating and axonal polyneuropathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001315","label":"Reduced tendon reflexes","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003390","label":"Sensory axonal neuropathy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0040131","label":"Abnormal motor nerve conduction velocity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003130","label":"Abnormal peripheral myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007230","label":"Decreased distal sensory nerve action potential","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009046","label":"Difficulty running","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003693","label":"Distal amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012378","label":"Fatigue","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012785","label":"Flexion contracture of finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004302","label":"Functional motor deficit","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010830","label":"Impaired tactile sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002495","label":"Impaired vibratory sensation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009473","label":"Joint contracture of the hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007002","label":"Motor axonal neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008948","label":"Proximal upper limb amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003474","label":"Somatic sensory dysfunction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009129","label":"Upper limb amyotrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003484","label":"Upper limb muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002493","label":"Upper motor neuron dysfunction","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012447","label":"Abnormal myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007703","label":"Abnormality of retinal pigmentation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002167","label":"Abnormality of speech or vocalization","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001620","label":"Abnormally high-pitched voice","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001047","label":"Atopic dermatitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006827","label":"Atrophy of the spinal cord","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012444","label":"Brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005879","label":"Congenital finger flexion contractures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008959","label":"Distal upper limb muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007641","label":"Dyschromatopsia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002380","label":"Fasciculations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009027","label":"Foot dorsiflexor weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003324","label":"Generalized muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030237","label":"Hand muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003797","label":"Limb-girdle muscle atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003325","label":"Limb-girdle muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003394","label":"Muscle spasm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002411","label":"Myokymia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000467","label":"Neck muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006970","label":"Periventricular leukomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003701","label":"Proximal muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008994","label":"Proximal muscle weakness in lower limbs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008997","label":"Proximal muscle weakness in upper limbs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007269","label":"Spinal muscular atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012473","label":"Tongue atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031947","label":"Tongue tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006597","label":"Diaphragmatic paralysis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002747","label":"Respiratory insufficiency due to muscle weakness","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000020","label":"Urinary incontinence","frequency":"Very rare (<4-1%)","criteria":null}]}}