Cargando…

Recent advances in understanding congenital myopathies

By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital my...

Descripción completa

Detalles Bibliográficos
Autores principales: Ravenscroft, Gianina, Bryson-Richardson, Robert J., Nowak, Kristen J., Laing, Nigel G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290972/
https://www.ncbi.nlm.nih.gov/pubmed/30631434
http://dx.doi.org/10.12688/f1000research.16422.1
_version_ 1783380181349564416
author Ravenscroft, Gianina
Bryson-Richardson, Robert J.
Nowak, Kristen J.
Laing, Nigel G.
author_facet Ravenscroft, Gianina
Bryson-Richardson, Robert J.
Nowak, Kristen J.
Laing, Nigel G.
author_sort Ravenscroft, Gianina
collection PubMed
description By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital myopathies when mutated, and a burst of new causative genes have been identified because of advances in gene sequencing technology. Recent discoveries include extending the disease phenotypes associated with previously identified genes and determining that genes formerly known to cause only dominant disease can also cause recessive disease. The more recently identified congenital myopathy genes account for only a small proportion of patients. Thus, the congenital myopathy genes remaining to be discovered are predicted to be extremely rare causes of disease, which greatly hampers their identification. Significant progress in the provision of molecular diagnoses brings important information and value to patients and their families, such as possible disease prognosis, better disease management, and informed reproductive choice, including carrier screening of parents. Additionally, from accurate genetic knowledge, rational treatment options can be hypothesised and subsequently evaluated in vitro and in animal models. A wide range of potential congenital myopathy therapies have been investigated on the basis of improved understanding of disease pathomechanisms, and some therapies are in clinical trials. Although large hurdles remain, promise exists for translating treatment benefits from preclinical models to patients with congenital myopathy, including harnessing proven successes for other genetic diseases.
format Online
Article
Text
id pubmed-6290972
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher F1000 Research Limited
record_format MEDLINE/PubMed
spelling pubmed-62909722019-01-09 Recent advances in understanding congenital myopathies Ravenscroft, Gianina Bryson-Richardson, Robert J. Nowak, Kristen J. Laing, Nigel G. F1000Res Review By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital myopathies when mutated, and a burst of new causative genes have been identified because of advances in gene sequencing technology. Recent discoveries include extending the disease phenotypes associated with previously identified genes and determining that genes formerly known to cause only dominant disease can also cause recessive disease. The more recently identified congenital myopathy genes account for only a small proportion of patients. Thus, the congenital myopathy genes remaining to be discovered are predicted to be extremely rare causes of disease, which greatly hampers their identification. Significant progress in the provision of molecular diagnoses brings important information and value to patients and their families, such as possible disease prognosis, better disease management, and informed reproductive choice, including carrier screening of parents. Additionally, from accurate genetic knowledge, rational treatment options can be hypothesised and subsequently evaluated in vitro and in animal models. A wide range of potential congenital myopathy therapies have been investigated on the basis of improved understanding of disease pathomechanisms, and some therapies are in clinical trials. Although large hurdles remain, promise exists for translating treatment benefits from preclinical models to patients with congenital myopathy, including harnessing proven successes for other genetic diseases. F1000 Research Limited 2018-12-11 /pmc/articles/PMC6290972/ /pubmed/30631434 http://dx.doi.org/10.12688/f1000research.16422.1 Text en Copyright: © 2018 Ravenscroft G et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Ravenscroft, Gianina
Bryson-Richardson, Robert J.
Nowak, Kristen J.
Laing, Nigel G.
Recent advances in understanding congenital myopathies
title Recent advances in understanding congenital myopathies
title_full Recent advances in understanding congenital myopathies
title_fullStr Recent advances in understanding congenital myopathies
title_full_unstemmed Recent advances in understanding congenital myopathies
title_short Recent advances in understanding congenital myopathies
title_sort recent advances in understanding congenital myopathies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290972/
https://www.ncbi.nlm.nih.gov/pubmed/30631434
http://dx.doi.org/10.12688/f1000research.16422.1
work_keys_str_mv AT ravenscroftgianina recentadvancesinunderstandingcongenitalmyopathies
AT brysonrichardsonrobertj recentadvancesinunderstandingcongenitalmyopathies
AT nowakkristenj recentadvancesinunderstandingcongenitalmyopathies
AT laingnigelg recentadvancesinunderstandingcongenitalmyopathies