Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study

Introduction: Congenital myasthenic syndromes (CMS) refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies...

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Authors: Della Marina, Adela, Wibbeler, Eva, Abicht, Angela, Kölbel, Heike, Lochmüller, Hanns, Roos, Andreas, Schara-Schmidt, Ulrike
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/52966
Online Access:http://hdl.handle.net/10230/52966
http://dx.doi.org/10.3389/fnhum.2020.560860
Access Level:Open access
Keyword:Pediatria
Malalties neuromusculars en el infants
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oai_identifier_str oai:recercat.cat:10230/52966
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
title Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
spellingShingle Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
Della Marina, Adela
Pediatria
Malalties neuromusculars en el infants
title_short Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
title_full Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
title_fullStr Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
title_full_unstemmed Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
title_sort Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort study
dc.creator.none.fl_str_mv Della Marina, Adela
Wibbeler, Eva
Abicht, Angela
Kölbel, Heike
Lochmüller, Hanns
Roos, Andreas
Schara-Schmidt, Ulrike
author Della Marina, Adela
author_facet Della Marina, Adela
Wibbeler, Eva
Abicht, Angela
Kölbel, Heike
Lochmüller, Hanns
Roos, Andreas
Schara-Schmidt, Ulrike
author_role author
author2 Wibbeler, Eva
Abicht, Angela
Kölbel, Heike
Lochmüller, Hanns
Roos, Andreas
Schara-Schmidt, Ulrike
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Pediatria
Malalties neuromusculars en el infants
topic Pediatria
Malalties neuromusculars en el infants
description Introduction: Congenital myasthenic syndromes (CMS) refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies on disease progression and treatment-response in pediatric patients are rare. Patients and Methods: We analyzed retrospective clinical and medication data in a cohort of 32 CMS-patients including the application of a standardized, not yet validated test (CMS-ST) to examine muscular strength and endurance in 21 patients at the last follow-up. Findings obtained in our cohort were compared with long-term follow-up studies of (adult) CMS-cohorts from the literature by considering the underlying molecular mechanisms. Outcomes of CMS-ST were compared to results of normal clinical assessment. Results: Thirty-two pediatric patients with defects in eight different CMS-genes were followed by a median time of 12.8 years. Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants. While 53% of patients presented a reduced walking distance, 34% were wheelchair-bound. Even under adequate therapy with pyridostigmine (PS) and 3,4-diaminopyridine, CHAT-mutations led to the progression of muscular weakness partly in combination with persistent respiratory and bulbar symptoms. RAPSN, CHRND, and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. CHAT and CHRNE patients required higher PS dosages, whereas RAPSN patients needed a lower mean dosage at the last follow-up. The benefits of short-term medication and long-term progression of symptoms were highly dependent on the specific genetic defect. CMS-ST was carried out in 17/21 patients, determined affected muscle groups including bulbar and ocular symptoms, some of which were not reported by the patients. Conclusions: Our findings and comparison with the literature- suggest a better treatment-response and less severe progression of symptoms present in patients suffering from mutations in CMS-genes directly associated with receptor deficiency, while patients with defects leading to synaptopathy and presynaptic defects tend to have worse outcomes. Assessment of affected muscular groups and clinical symptoms by CMS-ST may be a useful tool for optimal therapeutic management of the patients, especially for future clinical studies.
publishDate 2020
dc.date.none.fl_str_mv 2020
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/52966
http://dx.doi.org/10.3389/fnhum.2020.560860
url http://hdl.handle.net/10230/52966
http://dx.doi.org/10.3389/fnhum.2020.560860
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
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spelling Long term follow-up on pediatric cases with congenital myasthenic syndromes-a retrospective single centre cohort studyDella Marina, AdelaWibbeler, EvaAbicht, AngelaKölbel, HeikeLochmüller, HannsRoos, AndreasSchara-Schmidt, UlrikePediatriaMalalties neuromusculars en el infantsIntroduction: Congenital myasthenic syndromes (CMS) refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies on disease progression and treatment-response in pediatric patients are rare. Patients and Methods: We analyzed retrospective clinical and medication data in a cohort of 32 CMS-patients including the application of a standardized, not yet validated test (CMS-ST) to examine muscular strength and endurance in 21 patients at the last follow-up. Findings obtained in our cohort were compared with long-term follow-up studies of (adult) CMS-cohorts from the literature by considering the underlying molecular mechanisms. Outcomes of CMS-ST were compared to results of normal clinical assessment. Results: Thirty-two pediatric patients with defects in eight different CMS-genes were followed by a median time of 12.8 years. Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants. While 53% of patients presented a reduced walking distance, 34% were wheelchair-bound. Even under adequate therapy with pyridostigmine (PS) and 3,4-diaminopyridine, CHAT-mutations led to the progression of muscular weakness partly in combination with persistent respiratory and bulbar symptoms. RAPSN, CHRND, and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. CHAT and CHRNE patients required higher PS dosages, whereas RAPSN patients needed a lower mean dosage at the last follow-up. The benefits of short-term medication and long-term progression of symptoms were highly dependent on the specific genetic defect. CMS-ST was carried out in 17/21 patients, determined affected muscle groups including bulbar and ocular symptoms, some of which were not reported by the patients. Conclusions: Our findings and comparison with the literature- suggest a better treatment-response and less severe progression of symptoms present in patients suffering from mutations in CMS-genes directly associated with receptor deficiency, while patients with defects leading to synaptopathy and presynaptic defects tend to have worse outcomes. Assessment of affected muscular groups and clinical symptoms by CMS-ST may be a useful tool for optimal therapeutic management of the patients, especially for future clinical studies.HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279)Frontiers Media202220222020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/52966http://dx.doi.org/10.3389/fnhum.2020.560860reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglés© 2020 Della Marina, Wibbeler, Abicht, Kölbel, Lochmüller, Roos and Schara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/529662026-05-29T05:05:01Z
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