{"orpha":98909,"name":"Desminopathy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Desmin-related myofibrillar myopathy"],"definition":"A rare genetic skeletal muscle disease characterized by abnormal chimeric aggregates of desmin and other cytoskeletal proteins and granulofilamentous material at the ultrastructural level in muscle biopsies and variable clinical myopathological features, age of disease onset and rate of disease progression. Patients present with bilateral skeletal muscle weakness that starts in distal leg muscles and spreads proximally, sometimes involving trunk, neck flexors and facial muscles and often cardiomyopathy manifested by conduction blocks, arrhythmias, chronic heart failure, and sometimes tachyarrhythmia. Weakness eventually leads to wheelchair dependence. Respiratory insufficiency can be a major cause of disability and death, beginning with nocturnal hypoventilation with oxygen desaturation and progressing to daytime respiratory failure.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-98909/","orphanet_url":"https://www.orpha.net/en/disease/detail/98909","names":{"fr":{"name":"Desminopathie","synonyms":["Myopathie myofibrillaire liée à la desmine"],"definition":"Maladie génétique rare du muscle squelettique caractérisée par des agrégats chimériques anormaux de desmine et d'autres protéines du cytosquelette, ainsi que par un dépôts de matériel granulofilamenteux au niveau ultrastructural dans les biopsies musculaires, et par des caractéristiques cliniques de myopathie, un âge d'apparition et un taux de progression de la maladie variables. Les patients présentent une faiblesse bilatérale des muscles squelettiques qui commence dans les muscles distaux des jambes et s'étend dans le sens proximal, touchant parfois le tronc, les muscles fléchisseurs du cou et les muscles faciaux, et souvent une cardiomyopathie se manifestant par des blocs de conduction, des arythmies, une insuffisance cardiaque chronique et parfois une tachyarythmie. La faiblesse musculaire entraîne le confinement au fauteuil roulant. L'insuffisance respiratoire qui se manifeste d'abord par une hypoventilation nocturne avec hypoxie, puis évolue vers une insuffisance respiratoire diurne, est l'une des principales causes de déclin fonctionnel et peut conduire au décès."},"de":{"name":"Desminopathie","synonyms":["Myofibrilläre Myopathie, Desmin-assoziierte"]},"es":{"name":"Desminopatía","synonyms":["Miopatía miofibrilar asociada a la desmina"],"definition":"Es una enfermedad músculoesquelética, genética y poco frecuente, caracterizada por agregados quiméricos anómalos de desmina y otras proteínas citoesqueléticas y material granulofilamentoso a nivel ultraestructural en biopsias musculares, así como características clínicas / miopatológicas, edad de inicio y tasa de progresión de la enfermedad variables. Los afectados presentan debilidad muscular esquelética bilateral que comienza en los músculos distales de las piernas y progresa proximalmente, afectando ocasionalmente al tronco, los flexores del cuello y los músculos faciales. Con frecuencia, los afectados presentan miocardiopatía, que se manifiesta por bloqueos de conducción, arritmias, insuficiencia cardíaca crónica y, en ocasiones, taquiarritmia. La debilidad conduce eventualmente a dependencia de la silla de ruedas. La insuficiencia respiratoria puede ser una causa importante de discapacidad y fallecimiento, comenzando con hiperventilación nocturna con desaturación de oxígeno que progresa a insuficiencia respiratoria diurna."},"it":{"name":"Desminopatia","synonyms":["Miopatia miofibrillare legata alla desmina"],"definition":"La desminopatia è una malattia muscolo-scheletrica genetica rara, caratterizzata dalla presenza, a livello ultrastrutturale, di aggregati chimerici anomali di desmina e di altre proteine del citoscheletro e di materiali granulofilamentosi sulle biopsie muscolari, associati a segni clinici/miopatologici variabili, diversa età d'esordio e progressione della malattia. I pazienti presentano debolezza bilaterale dei muscoli scheletrici, che esordisce nei muscoli distali delle gambe e si estende successivamente ai muscoli prossimali, potendo occasionalmente interessare i muscoli del tronco, i flessori del collo e i muscoli facciali. Spesso si associa a cardiomiopatia, che si manifesta con blocchi della conduzione, aritmie, insufficienza cardiaca cronica e, talvolta, tachiaritmia. La debolezza costringe i pazienti alla sedia a rotelle. L'insufficienza respiratoria è una delle principali cause di disabilità e di morte; si manifesta con iperventilazione notturna associata a desaturazione dell'ossigeno per poi progredire verso l'insufficienza respiratoria diurna."},"nl":{"name":"Desminopathie","synonyms":["Desmine-gerelateerde myofibrillaire myopathie"],"definition":"Een zeldzame, genetische ziekte van skeletspieren, gekarakteriseerd door abnormale chimere aggregaten van desmine en andere proteïnen van het cytoskelet en granulofilamenteus materiaal op ultrastructureel niveau in spierbiopten, en variabele klinische/myopathologische kenmerken, aanvangsleeftijd en progressiesnelheid. Patiënten vertonen bilaterale zwakte van skeletspieren die aanvangt in distale beenspieren en proximaal verspreidt, soms met aantasting van romp, buigspieren van nek en aangezichtsspieren, en vaak ook cardiomyopathie die zich manifesteert met geleidingsstoornissen, hartritmestoornissen, chronisch hartfalen, en soms tachyaritmie. Spierzwakte resulteert uiteindelijk in afhankelijkheid van een rolstoel. Respiratoire insufficiëntie is mogelijk een voorname oorzaak van invaliditeit en overlijden, en begint met nachtelijke hyperventilatie met zuurstofdesaturatie om later te evolueren naar respiratoir falen overdag."},"pt":{"name":"Desminopatia"},"pl":{"name":"Desminopatia","synonyms":["Miopatia miofibrylarna związana z desminą"],"definition":"*Desminopatia jest rzadką, genetycznie uwarunkowaną chorobą mięśni szkieletowych, która charakteryzuje się zróżnicowanym obrazem klinicznym/zmianami patologicznymi w mięśniach, wiekiem wystąpienia i szybkością progresji objawów choroby, zaś na poziomie komórkowym - obecnością w bioptatach mięśni nieprawidłowych złogów desminy i innych białek cytoszkieletu oraz materiału ziarnisto-nitkowatego. U pacjentów występuje osłabienie mięśni szkieletowych, które rozpoczyna się w dystalnych mięśniach kończyn dolnych, a następnie obejmuje mięśnie proksymalne, czasami także tułów, zginacze szyi i mięśnie twarzy; często rozwija się kardiomiopatia, która manifestuje się zaburzeniami przewodnictwa, zaburzeniami rytmu serca, w tym tachyarytmią, oraz przewlekłą niewydolnością serca. Osłabienie mięśni ostatecznie prowadzi do niepełnosprawności ruchowej i utraty zdolności samodzielnego chodzenia. Upośledzenie funkcji układu oddechowego, które początkowo objawia się nocną hipowentylacją z hipoksją, a następnie postępuje aż do niewydolności oddechowej w dzień, jest jedną z głównych przyczyn pogorszenia sprawności i może prowadzić do zgonu."},"cs":{"name":"Desminopatie","synonyms":["Desmin-vázaná myofibrilární myopatie"]},"uk":{"name":"Десмінопатія","synonyms":["Міофібрилярна міопатія, повязана з десміном"],"definition":"A rare genetic skeletal muscle disease characterized by abnormal chimeric aggregates of desmin and other cytoskeletal proteins and granulofilamentous material at the ultrastructural level in muscle biopsies and variable clinical myopathological features, age of disease onset and rate of disease progression. Patients present with bilateral skeletal muscle weakness that starts in distal leg muscles and spreads proximally, sometimes involving trunk, neck flexors and facial muscles and often cardiomyopathy manifested by conduction blocks, arrhythmias, chronic heart failure, and sometimes tachyarrhythmia. Weakness eventually leads to wheelchair dependence. Respiratory insufficiency can be a major cause of disability and death, beginning with nocturnal hypoventilation with oxygen desaturation and progressing to daytime respiratory failure."},"zh":{"name":"结蛋白病","synonyms":["结蛋白相关肌原纤维肌病"],"definition":"该病是一种罕见的遗传性骨骼肌疾病，其特征是肌肉活检组织中的结蛋白和其他细胞骨架蛋白和颗粒膜物质在超微结构水平上出现异常的嵌合聚集体，并具有不同的临床肌肉病理学特征、发病年龄和疾病进展速度。患者出现双侧骨骼肌无力，始于小腿远端肌肉并向近端扩散，有时累及躯干、颈部屈肌和面部肌肉，通常表现为传导阻滞、心律失常、慢性心力衰竭，有时可表现为快速性心律失常。肌无力最终会需要使用轮椅，呼吸功能不全可能是致残和死亡的主要原因，患者从夜间低通气伴氧饱和度下降开始，发展到白天出现呼吸衰竭。"},"tr":{"name":"Desminopati","synonyms":["Desmin-ilişkili miyofibriler miyopati"]}},"xrefs":[{"source":"OMIM","code":"601419","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8C76","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"190618985"},{"source":"MONDO","code":"0011076","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C563319","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1832370","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Moved to","orpha":34517,"name":"Autosomal dominant limb-girdle muscular dystrophy type 1E","status":"inactive"},{"type":"Moved to","orpha":363543,"name":"Autosomal recessive limb-girdle muscular dystrophy type 2R","status":"inactive"}],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":206650,"name":"Autosomal dominant distal myopathy","classifications":[156,181]},{"orpha":217635,"name":"Familial restrictive cardiomyopathy","classifications":[146,156]},{"orpha":206662,"name":"Inclusion myopathy","classifications":[156,181]},{"orpha":593,"name":"Myofibrillar myopathy","classifications":[156,181]},{"orpha":217610,"name":"Neuromuscular disease with dilated cardiomyopathy","classifications":[146,156,233]},{"orpha":209041,"name":"Qualitative or quantitative defects of desmin","classifications":[156]},{"orpha":217595,"name":"Syndrome associated with hypertrophic cardiomyopathy","classifications":[146,156,233]}],"children":[],"genes":[{"symbol":"DES","name":"desmin","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"11668632[PMID]","hgnc":"2770","ensembl":"ENSG00000175084","omim":"125660","loci":["2q35"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["Adolescent","Adult","Childhood","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-01-14","source":"23143191[PMID]_7405006[PMID]_8509778[PMID]_8114783[PMID]_15122708[PMID]","terms":[{"hpo":"HP:0003327","label":"Axial muscle weakness","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:0003323","label":"Progressive muscle weakness","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001678","label":"Atrioventricular block","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005157","label":"Concentric hypertrophic cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030196","label":"Fatigable weakness of respiratory muscles","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002505","label":"Loss of ambulation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002747","label":"Respiratory insufficiency due to muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005115","label":"Supraventricular arrhythmia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002522","label":"Areflexia of lower limbs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030192","label":"Fatigable weakness of bulbar muscles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003722","label":"Neck flexor weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001645","label":"Sudden cardiac death","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005659","label":"Thoracic kyphoscoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030319","label":"Weakness of facial musculature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003306","label":"Spinal rigidity","frequency":"Very rare (<4-1%)","criteria":null}]}}