{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:02:06Z","timestamp":1782705726097,"version":"3.54.5"},"reference-count":32,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2023,3,7]]},"abstract":"<jats:p>We here present the case of a patient with a congenital myasthenic syndrome (CMS) due to pathogenic variants in the RAPSN gene. During childhood he experienced recurrent episodes of respiratory failure during respiratory infections. This and other cases were reported as isolated dystrophy of the diaphragmatic musculature. In adulthood, whole exome sequencing revealed two heterozygous pathogenic variants in the RAPSN gene. This led to the revision of the diagnosis to rapsyn CMS11 (OMIM:616326, MONDO:0014588). EMG, muscle ultrasound and the revision of muscle biopsies taken in childhood support this diagnosis. After the revision of the diagnosis, treatment with pyridostigmine was started. This resulted in a reduction of fatigability and an improvement in functional abilities and quality of life.<\/jats:p>","DOI":"10.3233\/jnd-221542","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T11:42:33Z","timestamp":1672400553000},"page":"271-277","source":"Crossref","is-referenced-by-count":5,"title":["Dystrophic Myopathy of the Diaphragm with Recurrent Severe Respiratory Failure is Congenital Myasthenic Syndrome 11"],"prefix":"10.1177","volume":"10","author":[{"given":"J.J.","family":"Kramer","sequence":"first","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.T.M.","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.H.","family":"Leijten","sequence":"additional","affiliation":[{"name":"Rijnstate Hospital, Arnhem, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Ter Laak","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Eshuis","sequence":"additional","affiliation":[{"name":"Department of Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Kusters","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.L.M.","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.J.","family":"Kamsteeg","sequence":"additional","affiliation":[{"name":"Department of Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Eymard","sequence":"additional","affiliation":[{"name":"Institute de Myologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Doorduin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.C.","family":"Voermans","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"1","key":"10.3233\/JND-221542_ref1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0960-8966(93)90041-H","article-title":"Dystrophic myopathy of the diaphragm in a neonate with severe respiratory failure during infectious episodes","volume":"3","author":"Leyten","year":"1993","journal-title":"Neuromuscul Disord"},{"issue":"4","key":"10.3233\/JND-221542_ref2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/ana.410010414","article-title":"Isolated myopathic involvement of the diaphragmatic musculature in a neonate","volume":"1","author":"Bergen","year":"1977","journal-title":"Ann Neurol"},{"issue":"1","key":"10.3233\/JND-221542_ref3","first-page":"33","article-title":"Diaphragmatic paralysis due to partial diaphragmatic hypoplasia mimicking a localized muscular dystrophy: A case report","volume":"7","author":"Bosman","year":"1988","journal-title":"Clin Neuropathol"},{"issue":"4","key":"10.3233\/JND-221542_ref4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1159\/000114836","article-title":"A progressive congenital myopathy. Initial involvement of the diaphragm with type I muscle fiber atrophy","volume":"15","author":"De Reuck","year":"1977","journal-title":"Eur Neurol"},{"issue":"3","key":"10.3233\/JND-221542_ref5","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0022-3476(62)80063-8","article-title":"Muscular dystrophy in infancy: Report of 2 cases in siblings with diaphragmatic weakness","volume":"60","author":"Lewis","year":"1962","journal-title":"The Journal of Pediatrics"},{"issue":"4","key":"10.3233\/JND-221542_ref6","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S1474-4422(14)70201-7","article-title":"Congenital myasthenic syndromes: Pathogenesis, diagnosis, and treatment","volume":"14","author":"Engel","year":"2015","journal-title":"Lancet Neurol"},{"issue":"2","key":"10.3233\/JND-221542_ref7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1136\/practneurol-2012-000404","article-title":"Congenital myasthenic syndromes: An update","volume":"13","author":"Finlayson","year":"2013","journal-title":"Pract Neurol"},{"issue":"1","key":"10.3233\/JND-221542_ref8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13023-019-1025-5","article-title":"Congenital myasthenic syndromes","volume":"14","author":"Finsterer","year":"2019","journal-title":"Orphanet J Rare Dis"},{"issue":"5","key":"10.3233\/JND-221542_ref9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/WCO.0b013e328364dc0f","article-title":"Congenital myasthenic syndromes: An update","volume":"26","author":"Hanta\u00ef","year":"2013","journal-title":"Curr Opin Neurol"},{"issue":"5","key":"10.3233\/JND-221542_ref10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"4","key":"10.3233\/JND-221542_ref11","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1086\/339465","article-title":"Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome","volume":"70","author":"Ohno","year":"2002","journal-title":"Am J Hum Genet"},{"issue":"11","key":"10.3233\/JND-221542_ref12","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1212\/01.WNL.0000072262.14931.80","article-title":"Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients","volume":"60","author":"M\u00fcller","year":"2003","journal-title":"Neurology"},{"issue":"Pt 10","key":"10.3233\/JND-221542_ref13","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1093\/brain\/awl219","article-title":"Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations","volume":"129","author":"Cossins","year":"2006","journal-title":"Brain"},{"issue":"2","key":"10.3233\/JND-221542_ref14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3233\/JND-180376","article-title":"Panel-based exome sequencing for neuromuscular disorders as a diagnostic service","volume":"6","author":"Westra","year":"2019","journal-title":"J Neuromuscul Dis"},{"issue":"10","key":"10.3233\/JND-221542_ref15","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1002\/humu.22130","article-title":"Congenital myasthenic syndromes: Achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: A study of 680 patients","volume":"33","author":"Abicht","year":"2012","journal-title":"Hum Mutat"},{"issue":"1","key":"10.3233\/JND-221542_ref16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.braindev.2021.09.001","article-title":"Successful treatment of congenital myasthenic syndrome caused by a novel compound heterozygous variant in RAPSN","volume":"44","author":"Saito","year":"2022","journal-title":"Brain Dev"},{"issue":"5","key":"10.3233\/JND-221542_ref17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/humu.21438","article-title":"LOVD v.2.0: The next generation in gene variant databases","volume":"32","author":"Fokkema","year":"2011","journal-title":"Hum Mutat"},{"issue":"2","key":"10.3233\/JND-221542_ref18","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.nmd.2015.10.013","article-title":"Long-term follow-up in patients with congenital myasthenic syndrome due to RAPSN mutations","volume":"26","author":"Natera-de Benito","year":"2016","journal-title":"Neuromuscul Disord"},{"issue":"9","key":"10.3233\/JND-221542_ref19","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.eimc.2016.12.007","article-title":"Age distribution of acute respiratory infections caused by enteroviruses in the child population","volume":"35","author":"Reina","year":"2017","journal-title":"Enferm Infecc Microbiol Clin"},{"issue":"7","key":"10.3233\/JND-221542_ref20","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1017\/S0950268813002471","article-title":"Incidence of acute respiratory infections in Australia","volume":"142","author":"Chen","year":"2014","journal-title":"Epidemiol Infect"},{"key":"10.3233\/JND-221542_ref21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.spen.2017.03.006","article-title":"The curse of apneic spells","volume":"26","author":"Radke","year":"2018","journal-title":"Semin Pediatr Neurol"},{"issue":"4","key":"10.3233\/JND-221542_ref22","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1055\/s-2004-820993","article-title":"Congenital myasthenic syndrome due to rapsyn deficiency: Three cases with arthrogryposis and bulbar symptoms","volume":"35","author":"Ioos","year":"2004","journal-title":"Neuropediatrics"},{"issue":"5","key":"10.3233\/JND-221542_ref23","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.pediatrneurol.2014.07.032","article-title":"Use of next-generation sequencing as a diagnostic tool for congenital myasthenic syndrome","volume":"51","author":"Das","year":"2014","journal-title":"Pediatr Neurol"},{"issue":"1","key":"10.3233\/JND-221542_ref24","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.nmd.2003.07.002","article-title":"Electrophysiological and morphological characterization of a case of autosomal recessive congenital myasthenic syndrome with acetylcholine receptor deficiency due to a N88K rapsyn homozygous mutation","volume":"14","author":"Yasaki","year":"2004","journal-title":"Neuromuscul Disord"},{"issue":"3","key":"10.3233\/JND-221542_ref25","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/mus.10433","article-title":"Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering","volume":"28","author":"Maselli","year":"2003","journal-title":"Muscle Nerve"},{"issue":"3","key":"10.3233\/JND-221542_ref26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.nmd.2003.11.004","article-title":"Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine","volume":"14","author":"Banwell","year":"2004","journal-title":"Neuromuscul Disord"},{"key":"10.3233\/JND-221542_ref27","doi-asserted-by":"crossref","unstructured":"Xing G , et al. A mechanism in agrin signaling revealed by a prevalent Rapsyn mutation in congenital myasthenic syndrome. Elife. 2019;8.","DOI":"10.7554\/eLife.49180"},{"key":"10.3233\/JND-221542_ref28","doi-asserted-by":"crossref","first-page":"135013","DOI":"10.1016\/j.neulet.2020.135013","article-title":"Rapsyn as a signaling and scaffolding molecule in neuromuscular junction formation and maintenasnce","volume":"731","author":"Xing","year":"2020","journal-title":"Neurosci Lett"},{"issue":"10","key":"10.3233\/JND-221542_ref29","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2165\/00007256-200737100-00002","article-title":"Neutrophil infiltration in exercise-injured skeletal muscle: How do we resolve the controversy?","volume":"37","author":"Schneider","year":"2007","journal-title":"Sports Med"},{"key":"10.3233\/JND-221542_ref30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2044-5040-4-7","article-title":"Novel and optimized strategies for inducing fibrosis in vivo: Focus on Duchenne Muscular Dystrophy","volume":"4","author":"Pessina","year":"2014","journal-title":"Skelet Muscle"},{"issue":"2","key":"10.3233\/JND-221542_ref31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/mus.25035","article-title":"Muscle magnetic resonance imaging in congenital myasthenic syndromes","volume":"54","author":"Finlayson","year":"2016","journal-title":"Muscle Nerve"},{"issue":"6","key":"10.3233\/JND-221542_ref32","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1136\/archdischild-2013-304788","article-title":"How common is childhood myasthenia? The UK incidence and prevalence of autoimmune and congenital myasthenia","volume":"99","author":"Parr","year":"2014","journal-title":"Arch Dis Child"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-221542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:52:19Z","timestamp":1777506739000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-221542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":32,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jnd-221542","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]}}}