{"orpha":399081,"name":"KLHL9-related early-onset distal myopathy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"KLHL9-related early-onset distal myopathy is a rare, genetic distal myopathy characterized by slowly progressive distal limb muscle weakness and atrophy (beginning with anterior tibial muscle involvement followed by the intrinsic hand muscles) in association with reduced sensation in a stocking-glove distribution. Patients present with high stepping gait, ankle areflexia and contractures in the first to second decade of life, associated with marked ankle extensor muscle atrophy; later proximal muscle involvement is moderate and ambulation is preserved throughout the life.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-399081/","orphanet_url":"https://www.orpha.net/en/disease/detail/399081","names":{"fr":{"name":"Myopathie distale précoce associée à KLHL9","definition":"La myopathie distale précoce associée à KLHL9 est une myopathie génétique distale rare caractérisée par une faiblesse et une atrophie lentement progressives des muscles des membres distaux (commençant par les muscles tibiaux antérieurs, suivis des muscles intrinsèques de la main), associées à une perte de la sensibilité avec une distribution en gants et en chaussettes. Les patients présentent une marche à haut steppage, une aréflexie au niveau des chevilles, et des contractures apparaissant de la première à la deuxième décennie, associées à une atrophie prononcée des muscles extenseurs de la cheville. L'atteinte tardive des muscles proximaux est modérée, et la locomotion est préservée tout au long de la vie."},"de":{"name":"KLHL9-abhängige distale Myopathie mit Beginn in der Kindheit","definition":"Eine seltene, genetisch bedingte distale Myopathie, die durch eine langsam fortschreitende Muskelschwäche und -atrophie der distalen Gliedmaßen gekennzeichnet ist (beginnend mit einer Beteiligung der vorderen Schienbeinmuskulatur, gefolgt von der intrinsischen Handmuskulatur) in Verbindung mit typischen handschuh- bzw. strumpfförmigen Sensibilitätsstörungen. Die Patienten zeigen in der ersten bis zweiten Lebensdekade einen hohen Steppergang, Knöchelareflexie und Kontrakturen, verbunden mit einer ausgeprägten Knöchelstreckermuskelatrophie; später ist die proximale Muskelbeteiligung moderat und die Gehfähigkeit bleibt lebenslang erhalten."},"es":{"name":"Miopatía distal de inicio precoz asociada al gen KLHL9","definition":"La miopatía distal de inicio temprano asociada a <i>KLHL9</i> es una miopatía distal genética poco frecuente caracterizada por debilidad y atrofia muscular distal lentamente progresivas de las extremidades (comenzando con una afectación del músculo tibial anterior seguida por los músculos intrínsecos de la mano) en asociación con una disminución de sensibilidad en manos y pies (con distribución 'en guante y calcetín'). Los afectados presentan marcha en estepaje, arreflexia aquílea y contracturas en la primera a segunda décadas de vida, asociados con marcada atrofia de la musculatura extensora de tobillo; la afectación muscular proximal tardía es moderada y la deambulación se conserva a lo largo de la vida."},"it":{"name":"Miopatia distale correlata a KLHL9 ad esordio precoce","definition":"La miopatia distale correlata a KLHL9 ad esordio precoce è una miopatia distale rara di origine genetica, caratterizzata da debolezza e atrofia a progressione lenta dei muscoli della porzione distale degli arti (che esordisce nei muscoli tibiali anteriori per poi interessare anche i muscoli intrinsechi della mano), associate a una riduzione della sensibilità con una distribuzione a guanto. Durante la prima e seconda decade di vita, i pazienti presentano un'andatura a passi elevati, areflessia delle caviglie e contratture, associate a una marcata atrofia del muscolo estensore della caviglia; successivamente, l'interessamento dei muscoli prossimali risulta moderato e la deambulazione viene preservata per tutta la vita."},"nl":{"name":"KLHL9-gerelateerde distale myopathie met aanvang tijdens de kindertijd","definition":"KLHL9-gerelateerde distale myopathie in de kindertijd is een zeldzame, genetische distale myopathie die gekarakteriseerd wordt door traag progressieve spierzwakte en -atrofie in distale ledematen (te beginnen met betrokkenheid van anterieure scheenbeenspier, gevolgd door intrinsieke handspieren), in associatie met verminderde zintuiglijke waarneming volgens een kous-handschoen-verdeling. Patiënten vertonen hanentred, areflexie en contracturen van de enkel tijdens het eerste tot tweede levensdecennium, geassocieerd met duidelijke atrofie van de strekspier van de enkel; later is er matige betrokkenheid van proximale spieren en het stapvermogen blijft levenslang bewaard."},"pt":{"name":"Miopatia distal de início precoce KLHL9-relacionada","synonyms":["Miopatia distal com início na adolescência relacionada com KLHL9"]},"pl":{"name":"Dystalna miopatia zależna od KLHL9 o początku w dzieciństwie"},"cs":{"name":"KLHL9-vázaná distální myopatie s nástupem v dětském věku"},"uk":{"name":"Дистальна міопатія раннього початку, повязана з KLHL9","definition":"KLHL9-related early-onset distal myopathy is a rare, genetic distal myopathy characterized by slowly progressive distal limb muscle weakness and atrophy (beginning with anterior tibial muscle involvement followed by the intrinsic hand muscles) in association with reduced sensation in a stocking-glove distribution. Patients present with high stepping gait, ankle areflexia and contractures in the first to second decade of life, associated with marked ankle extensor muscle atrophy; later proximal muscle involvement is moderate and ambulation is preserved throughout the life."},"zh":{"name":"KLHL9相关早发性远端肌病","definition":"KLHL9相关性早发性远端肌病是一种罕见的遗传性远端肌病，其特征是缓慢进行性的远端肌无力和肌萎缩(先是胫前肌受累，随后是手部固有肌肉)，并伴有感觉减退。患者在生命的第一到第二个十年中出现步态过高、踝关节反射不全和挛缩，并伴有明显的踝伸肌萎缩；随后近端肌肉可中度受累，患者行走能力可终身始终保持。"},"tr":{"name":"KLHL9-ilişkili erken-başlangıçlı distal miyopati"}},"xrefs":[{"source":"ICD-10","code":"G71.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018370","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4706574","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":206650,"name":"Autosomal dominant distal myopathy","classifications":[156,181]}],"children":[],"genes":[{"symbol":"KLHL9","name":"kelch like family member 9","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20554658[PMID]","hgnc":"18732","ensembl":"ENSG00000198642","omim":"611201","loci":["9p21.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Adolescent","Childhood"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"20554658[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_20554658[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-01-14","source":"20554658[PMID]","terms":[{"hpo":"HP:0006466","label":"Ankle flexion contracture","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002936","label":"Distal sensory impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003458","label":"EMG: myopathic abnormalities","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0009063","label":"Progressive distal muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0009005","label":"Weakness of the intrinsic hand muscles","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0040081","label":"Abnormal circulating creatine kinase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001430","label":"Abnormality of the calf musculature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006844","label":"Absent patellar reflexes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009031","label":"Amyotrophy of ankle musculature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006937","label":"Impaired distal tactile sensation","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:0008954","label":"Intrinsic hand muscle atrophy","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:0002505","label":"Loss of ambulation","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003477","label":"Peripheral axonal neuropathy","frequency":"Very rare (<4-1%)","criteria":null}]}}