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Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions

Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when muta...

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Autores principales: Nicole, Sophie, Azuma, Yoshiteru, Bauché, Stéphanie, Eymard, Bruno, Lochmüller, Hanns, Slater, Clarke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701762/
https://www.ncbi.nlm.nih.gov/pubmed/29125502
http://dx.doi.org/10.3233/JND-170257
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author Nicole, Sophie
Azuma, Yoshiteru
Bauché, Stéphanie
Eymard, Bruno
Lochmüller, Hanns
Slater, Clarke
author_facet Nicole, Sophie
Azuma, Yoshiteru
Bauché, Stéphanie
Eymard, Bruno
Lochmüller, Hanns
Slater, Clarke
author_sort Nicole, Sophie
collection PubMed
description Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models. Frontier forms between CMS and congenital myopathy, which have been genetically and clinically identified, underline the poorly understood interplay between the synaptic and extrasynaptic molecules in the neuromuscular system. In addition, precise electrophysiological and histopathological investigations of individuals with CMS suggest an important role of NMJ plasticity in the response to CMS pathogenesis. While efficient drug-based treatments are already available to improve neuromuscular transmission for most forms of CMS, others, as well as neurological and muscular comorbidities, remain resistant. Taken together, the available pathological data point to physiological issues which remain to be understood in order to achieve precision medicine with efficient therapeutics for all individuals suffering from CMS.
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spelling pubmed-57017622017-11-28 Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions Nicole, Sophie Azuma, Yoshiteru Bauché, Stéphanie Eymard, Bruno Lochmüller, Hanns Slater, Clarke J Neuromuscul Dis Review Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models. Frontier forms between CMS and congenital myopathy, which have been genetically and clinically identified, underline the poorly understood interplay between the synaptic and extrasynaptic molecules in the neuromuscular system. In addition, precise electrophysiological and histopathological investigations of individuals with CMS suggest an important role of NMJ plasticity in the response to CMS pathogenesis. While efficient drug-based treatments are already available to improve neuromuscular transmission for most forms of CMS, others, as well as neurological and muscular comorbidities, remain resistant. Taken together, the available pathological data point to physiological issues which remain to be understood in order to achieve precision medicine with efficient therapeutics for all individuals suffering from CMS. IOS Press 2017-11-21 /pmc/articles/PMC5701762/ /pubmed/29125502 http://dx.doi.org/10.3233/JND-170257 Text en © 2017 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Nicole, Sophie
Azuma, Yoshiteru
Bauché, Stéphanie
Eymard, Bruno
Lochmüller, Hanns
Slater, Clarke
Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions
title Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions
title_full Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions
title_fullStr Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions
title_full_unstemmed Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions
title_short Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions
title_sort congenital myasthenic syndromes or inherited disorders of neuromuscular transmission: recent discoveries and open questions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701762/
https://www.ncbi.nlm.nih.gov/pubmed/29125502
http://dx.doi.org/10.3233/JND-170257
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