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Lookup NU author(s): Dr Yoshiteru Azuma, Professor Hanns Lochmuller, Emeritus Professor Clarke Slater
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Nicole S, Azuma Y, Bauché S, Eymard B, Lochmüller H, Slater C
Publication type: Article
Publication status: Published
Journal: Journal of Neuromuscular Diseases
Year: 2017
Volume: 4
Issue: 4
Pages: 269-284
Online publication date: 21/11/2017
Acceptance date: 16/10/2017
Date deposited: 18/01/2018
ISSN (print): 2214-3599
ISSN (electronic): 2214-3602
Publisher: IOS Press
URL: https://doi.org/10.3233/JND-170257
DOI: 10.3233/JND-170257
PubMed id: 29125502
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