{"orpha":99741,"name":"King-Denborough syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Koussef-Nichols syndrome"],"definition":"King-Denborough syndrome is a rare genetic non-dystrophic myopathy characterized by the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia. Patients present with a wide phenotypic range, including delayed motor development, muscle weakness and fatigability, ptosis and facies myopathica (with or without creatine kinase elevations), skeletal abnormalities (e.g. short stature, scoliosis, kyphosis, lumbar lordosis and pectus carinatum/excavatum), mild dysmorphic facial features (e.g. hypertelorism, down-slanting palpebral fissures, epicanthic folds, low set ears, micrognathia), webbing of the neck, cryptorchidism, and a susceptibility to malignant hyperthermia and/or rhabdomyolysis due to intensive physical strain, viral infection or statin use.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-99741/","orphanet_url":"https://www.orpha.net/en/disease/detail/99741","names":{"fr":{"name":"Syndrome de King-Denborough","synonyms":["Syndrome de Koussef-Nichols"],"definition":"Une myopathie génétique rare, non dystrophique, caractérisée par la triade de myopathie congénitale, dysmorphie et susceptibilité à l'hyperthermie maligne. Les patients présentent un phénotype large qui inclut un retard de développement moteur, une faiblesse et une fatigabilité musculaires, un ptosis et un faciès myopathique (avec ou sans élévation de la créatine kinase), des anomalies squelettiques (comme une petite taille, une scoliose, une cyphose, une lordose lombaire et un pectus carinatum/excavatum), une légère dysmorphie faciale (hypertélorisme, fentes palpébrales obliques en bas et en dehors, plis épicanthiques, oreilles basses implantées, micrognathie), un cou palmé, une cryptorchidie et une susceptibilité à l'hyperthermie maligne et/ou à la rhabdomyolyse causée par un effort physique intense, une infection virale ou l'utilisation de statine."},"de":{"name":"King-Denborough-Syndrom","synonyms":["Koussef-Nichols-Syndrom"],"definition":"Das King-Denborough-Syndrom ist eine seltene, genetische, nicht-dystrophische Myopathie, die sich aus der Trias von kongenitaler Myopathie, dysmorphen Merkmalen und Anfälligkeit für maligne Hyperthermie zusammensetzt. Die Patienten zeigen ein breites Spektrum an Phänotypen, einschließlich verzögerter motorischer Entwicklung, Muskelschwäche und schnelle Ermüdbarkeit, Ptosis und Facies myopathica (mit oder ohne Kreatinkinase-Erhöhung), Skelettanomalien (z. B. Kleinwuchs, Skoliose, Kyphose, Lendenlordose und Pectus carinatum/excavatum), milde dysmorphe Gesichtszüge (z. B. Hypertelorismus, schräg nach unten verlaufende Lidspalten, Epikanthusfalten, tief angesetzte Ohren, Mikrognathie), Pterygium colli, Kryptorchismus und eine Anfälligkeit für maligne Hyperthermie und/oder Rhabdomyolyse infolge intensiver körperlicher Belastung, viraler Infektion oder Statin-Einnahme."},"es":{"name":"Síndrome de King-Denborough","synonyms":["Síndrome de Koussef-Nichols"],"definition":"El síndrome de King-Denborough es una miopatía no distrófica genética y poco frecuente, caracterizada por la tríada de miopatía congénita, rasgos dismórficos y susceptibilidad a la hipertermia maligna. Los afectados presentan un amplio rango fenotípico, que incluye retraso del desarrollo motor, debilidad muscular y fatiga, ptosis y facies miopática (con o sin aumento de creatina quinasa), anomalías esqueléticas (por ejemplo, talla baja, escoliosis, cifosis, lordosis lumbar y pectus carinatum/excavatum), rasgos faciales dismórficos leves (p. ej., hipertelorismo, fisuras palpebrales inclinadas hacia abajo, pliegues epicánticos, orejas de baja implantación baja, micrognatia), pliegues en el cuello, criptorquidia y susceptibilidad a hipertermia maligna y/o rabdomiolisis debida a esfuerzo físico intenso, infección viral o al uso de estatinas."},"it":{"name":"Sindrome di King-Denborough","synonyms":["Sindrome di Koussef-Nichols"],"definition":"La sindrome di King-Denborough è una miopatia non distrofica rara di origine genetica, caratterizzata dalla triade miopatia congenita, dismorfismi e suscettibilità all'ipertermia maligna. I pazienti presentano un quadro clinico molto variabile, che comprende il ritardo dello sviluppo motorio, la debolezza muscolare e l'affaticamento, la ptosi e la facies miopatica (con o senza aumento dei livelli di creatina chinasi), anomalie scheletriche (bassa statura, scoliosi, cifosi, lordosi lombare e pectus carinatum/excavatum), dismorfismi facciali sfumati (ipertelorismo, rime palpebrali oblique verso il basso, epicanto, orecchie a basso impianto, micrognazia), plicatura del collo, criptorchidismo e suscettibilità all'ipertermia maligna e/o alla rabdomiolisi indotta dallo stress fisico intenso, dalle infezioni virali o dall'assunzione di statine."},"nl":{"name":"Syndroom van King-Denborough","synonyms":["Syndroom van Koussef-Nichols"],"definition":"Syndroom van King-Denborough is een zeldzame, genetische niet-dystrofische myopathie die gekarakteriseerd wordt door de triade van congenitale myopathie, dysmorfe kenmerken en vatbaarheid voor maligne hyperthermie. Patiënten vertonen een brede waaier van fenotypes, waaronder vertraagde motorische ontwikkeling, verzwakte en vermoeide spieren, ptose en facies myopathica (met of zonder toename van creatinekinase), skeletafwijkingen (e.g. kleine gestalte, scoliose, kyfose, lumbale lordose en pectus carinatum/excavatum), milde dysmorfe gelaatskenmerken (e.g. hypertelorisme, neerwaartse ooglidspleten, epicanthusplooien, laagstaande oren, micrognathie), huidplooien in de nek, cryptorchidie, en een vatbaarheid voor maligne hyperthermie en/of rabdomyolyse als gevolg van intensieve fysieke inspanning, virale infectie of gebruik van statines."},"pt":{"name":"Síndrome de King-Denborough"},"pl":{"name":"Zespół Kinga i Denborougha","synonyms":["Zespół Koussefa i Nicholsa","Zespół Koussefa i Nicholsa"]},"cs":{"name":"Kingův-Denboroughův syndrom","synonyms":["Koussefův-Nicholsův syndrom","King-Denboroughův syndrom","Koussef-Nicholsův syndrom"]},"uk":{"name":"Синдром Кінга-Денборо","synonyms":["Синдром Куссефа-Ніколса"],"definition":"King-Denborough syndrome is a rare genetic non-dystrophic myopathy characterized by the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia. Patients present with a wide phenotypic range, including delayed motor development, muscle weakness and fatigability, ptosis and facies myopathica (with or without creatine kinase elevations), skeletal abnormalities (e.g. short stature, scoliosis, kyphosis, lumbar lordosis and pectus carinatum/excavatum), mild dysmorphic facial features (e.g. hypertelorism, down-slanting palpebral fissures, epicanthic folds, low set ears, micrognathia), webbing of the neck, cryptorchidism, and a susceptibility to malignant hyperthermia and/or rhabdomyolysis due to intensive physical strain, viral infection or statin use."},"zh":{"name":"King-Denborough综合征","synonyms":["Koussef-Nichols 综合征"],"definition":"King-Denborough综合征是一种罕见的遗传性非营养不良性肌病，以先天性肌病、畸形特征和恶性高热易感为特征。患者的表型多样，包括运动发育迟缓、肌无力和肌肉疲劳、上睑下垂和肌病面容(伴或不伴肌酸激酶升高)、骨骼异常(如身材矮小、脊柱侧凸、后凸、鸡胸/漏斗胸)、轻度面部畸形特征(如眼距过宽、睑裂下斜、内睑赘皮、低位耳、小颌畸形)。"},"tr":{"name":"King-Denborough sendromu","synonyms":["Koussef-Nichols sendromu"]}},"xrefs":[{"source":"OMIM","code":"619542","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.2","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8C72.Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1140335303"},{"source":"MONDO","code":"0020485","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536883","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1840365","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"8433","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":97245,"name":"Congenital myopathy","classifications":[156,181]},{"orpha":183570,"name":"Genetic malformation syndrome with short stature","classifications":[156]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":139021,"name":"Malformation syndrome with short stature","classifications":[147]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":98742,"name":"Neurological muscular channelopathy due to a genetic ryanodine receptor defect","classifications":[156,181]},{"orpha":466658,"name":"Rare disease with malignant hyperthermia","classifications":[181]}],"children":[],"genes":[{"symbol":"RYR1","name":"ryanodine receptor 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21514828[PMID]_18765655[PMID]","hgnc":"10483","ensembl":"ENSG00000196218","omim":"180901","loci":["19q13.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Antenatal","Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":18.0,"area":"Worldwide","status":"Validated","source":"12738133[PMID]_18765655[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_12738133[PMID]_18765655[PMID]"}],"phenotypes":null}