Cargando…
The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes
Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032286/ https://www.ncbi.nlm.nih.gov/pubmed/29874875 http://dx.doi.org/10.3390/ijms19061677 |
_version_ | 1783337479022051328 |
---|---|
author | Rodríguez Cruz, Pedro M. Palace, Jacqueline Beeson, David |
author_facet | Rodríguez Cruz, Pedro M. Palace, Jacqueline Beeson, David |
author_sort | Rodríguez Cruz, Pedro M. |
collection | PubMed |
description | Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5A7 and SLC18A3, impairing the synthesis and recycling of acetylcholine, have recently been described. In addition, a novel group of CMS due to mutations in SNAP25B, SYT2, VAMP1, and UNC13A1 encoding molecules implicated in synaptic vesicles exocytosis has been characterised. The increasing number of presynaptic CMS exhibiting CNS manifestations along with neuromuscular weakness demonstrate that the myasthenia can be only a small part of a much more extensive disease phenotype. Moreover, the spectrum of glycosylation abnormalities has been increased with the report that GMPPB mutations can cause CMS, thus bridging myasthenic disorders with dystroglycanopathies. Finally, the discovery of COL13A1 mutations and laminin α5 deficiency has helped to draw attention to the role of extracellular matrix proteins for the formation and maintenance of muscle endplates. The benefit of β2-adrenergic agonists alone or combined with pyridostigmine or 3,4-Dyaminopiridine is increasingly being reported for different subtypes of CMS including AChR-deficiency and glycosylation abnormalities, thus expanding the therapeutic repertoire available. |
format | Online Article Text |
id | pubmed-6032286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60322862018-07-13 The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes Rodríguez Cruz, Pedro M. Palace, Jacqueline Beeson, David Int J Mol Sci Review Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5A7 and SLC18A3, impairing the synthesis and recycling of acetylcholine, have recently been described. In addition, a novel group of CMS due to mutations in SNAP25B, SYT2, VAMP1, and UNC13A1 encoding molecules implicated in synaptic vesicles exocytosis has been characterised. The increasing number of presynaptic CMS exhibiting CNS manifestations along with neuromuscular weakness demonstrate that the myasthenia can be only a small part of a much more extensive disease phenotype. Moreover, the spectrum of glycosylation abnormalities has been increased with the report that GMPPB mutations can cause CMS, thus bridging myasthenic disorders with dystroglycanopathies. Finally, the discovery of COL13A1 mutations and laminin α5 deficiency has helped to draw attention to the role of extracellular matrix proteins for the formation and maintenance of muscle endplates. The benefit of β2-adrenergic agonists alone or combined with pyridostigmine or 3,4-Dyaminopiridine is increasingly being reported for different subtypes of CMS including AChR-deficiency and glycosylation abnormalities, thus expanding the therapeutic repertoire available. MDPI 2018-06-05 /pmc/articles/PMC6032286/ /pubmed/29874875 http://dx.doi.org/10.3390/ijms19061677 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Rodríguez Cruz, Pedro M. Palace, Jacqueline Beeson, David The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes |
title | The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes |
title_full | The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes |
title_fullStr | The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes |
title_full_unstemmed | The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes |
title_short | The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes |
title_sort | neuromuscular junction and wide heterogeneity of congenital myasthenic syndromes |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032286/ https://www.ncbi.nlm.nih.gov/pubmed/29874875 http://dx.doi.org/10.3390/ijms19061677 |
work_keys_str_mv | AT rodriguezcruzpedrom theneuromuscularjunctionandwideheterogeneityofcongenitalmyasthenicsyndromes AT palacejacqueline theneuromuscularjunctionandwideheterogeneityofcongenitalmyasthenicsyndromes AT beesondavid theneuromuscularjunctionandwideheterogeneityofcongenitalmyasthenicsyndromes AT rodriguezcruzpedrom neuromuscularjunctionandwideheterogeneityofcongenitalmyasthenicsyndromes AT palacejacqueline neuromuscularjunctionandwideheterogeneityofcongenitalmyasthenicsyndromes AT beesondavid neuromuscularjunctionandwideheterogeneityofcongenitalmyasthenicsyndromes |