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Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models

Presynaptic congenital myasthenic syndromes (CMS) are a group of genetic disorders affecting the presynaptic side of the neuromuscular junctions (NMJ). They can result from a dysfunction in acetylcholine (ACh) synthesis or recycling, in its packaging into synaptic vesicles, or its subsequent release...

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Autores principales: Pugliese, Alessia, Holland, Stephen H., Rodolico, Carmelo, Lochmüller, Hanns, Spendiff, Sally
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578258/
https://www.ncbi.nlm.nih.gov/pubmed/37212067
http://dx.doi.org/10.3233/JND-221646
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author Pugliese, Alessia
Holland, Stephen H.
Rodolico, Carmelo
Lochmüller, Hanns
Spendiff, Sally
author_facet Pugliese, Alessia
Holland, Stephen H.
Rodolico, Carmelo
Lochmüller, Hanns
Spendiff, Sally
author_sort Pugliese, Alessia
collection PubMed
description Presynaptic congenital myasthenic syndromes (CMS) are a group of genetic disorders affecting the presynaptic side of the neuromuscular junctions (NMJ). They can result from a dysfunction in acetylcholine (ACh) synthesis or recycling, in its packaging into synaptic vesicles, or its subsequent release into the synaptic cleft. Other proteins involved in presynaptic endplate development and maintenance can also be impaired. Presynaptic CMS usually presents during the prenatal or neonatal period, with a severe phenotype including congenital arthrogryposis, developmental delay, and apnoeic crisis. However, milder phenotypes with proximal muscle weakness and good response to treatment have been described. Finally, many presynaptic genes are expressed in the brain, justifying the presence of additional central nervous system symptoms. Several animal models have been developed to study CMS, providing the opportunity to identify disease mechanisms and test treatment options. In this review, we describe presynaptic CMS phenotypes with a focus on in vivo models, to better understand CMS pathophysiology and define new causative genes.
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spelling pubmed-105782582023-10-17 Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models Pugliese, Alessia Holland, Stephen H. Rodolico, Carmelo Lochmüller, Hanns Spendiff, Sally J Neuromuscul Dis Review Presynaptic congenital myasthenic syndromes (CMS) are a group of genetic disorders affecting the presynaptic side of the neuromuscular junctions (NMJ). They can result from a dysfunction in acetylcholine (ACh) synthesis or recycling, in its packaging into synaptic vesicles, or its subsequent release into the synaptic cleft. Other proteins involved in presynaptic endplate development and maintenance can also be impaired. Presynaptic CMS usually presents during the prenatal or neonatal period, with a severe phenotype including congenital arthrogryposis, developmental delay, and apnoeic crisis. However, milder phenotypes with proximal muscle weakness and good response to treatment have been described. Finally, many presynaptic genes are expressed in the brain, justifying the presence of additional central nervous system symptoms. Several animal models have been developed to study CMS, providing the opportunity to identify disease mechanisms and test treatment options. In this review, we describe presynaptic CMS phenotypes with a focus on in vivo models, to better understand CMS pathophysiology and define new causative genes. IOS Press 2023-09-08 /pmc/articles/PMC10578258/ /pubmed/37212067 http://dx.doi.org/10.3233/JND-221646 Text en © 2023 – The authors. Published by IOS Press 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
Pugliese, Alessia
Holland, Stephen H.
Rodolico, Carmelo
Lochmüller, Hanns
Spendiff, Sally
Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models
title Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models
title_full Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models
title_fullStr Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models
title_full_unstemmed Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models
title_short Presynaptic Congenital Myasthenic Syndromes: Understanding Clinical Phenotypes through In vivo Models
title_sort presynaptic congenital myasthenic syndromes: understanding clinical phenotypes through in vivo models
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578258/
https://www.ncbi.nlm.nih.gov/pubmed/37212067
http://dx.doi.org/10.3233/JND-221646
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