MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Curr Opin Neurol. 2019 Oct;32(5):641-650. doi: 10.1097/WCO.0000000000000735.
Charcot-Marie-Tooth (CMT) disease and related disorders are the commonest group of inherited neuromuscular diseases and represent a heterogeneous group of disorders. This review will cover recent advances in genetic diagnosis and the evolving genetic and phenotype landscape of this disease group. We will review recent evidence of the increasingly recognized phenotypic overlap with other neurodegenerative conditions including hereditary spastic paraplegia, hereditary ataxias and mitochondrial diseases and highlight the importance of deep phenotyping to inform genetic diagnosis and prognosis.
Through whole exome sequencing and multicentre collaboration new genes are being identified as causal for CMT expanding the genetic heterogeneity of this condition. In addition, an increasing number of variants have been identified in genes known to cause complex inherited diseases in which the peripheral neuropathy is part of the disorder and may be the presenting feature. The recent discovery of a repeat expansion in the RFC1 gene in cerebellar ataxia, neuropathy, vestibular areflexia syndrome highlights the prevalence of late-onset recessive conditions which have historically been considered to cause early-onset disease.
CMT is an evolving field with considerable phenotypic and genetic heterogeneity and deep phenotyping remains a cornerstone in contemporary CMT diagnostics.
Charcot-Marie-Tooth (CMT) 疾病和相关疾病是最常见的遗传性神经肌肉疾病群体，代表了一组异质性疾病。本综述将涵盖遗传诊断的最新进展以及该疾病群体遗传和表型不断变化的图景。我们将回顾最近关于与其他神经退行性疾病（包括遗传性痉挛性截瘫、遗传性共济失调和线粒体疾病）日益认识到的表型重叠的证据，并强调深入表型分析对遗传诊断和预后的重要性。
通过全外显子组测序和多中心合作，新的基因被确定为 CMT 的致病原因，扩大了该疾病的遗传异质性。此外，在已知导致复杂遗传性疾病的基因中，越来越多的变异被发现，其中周围神经病是该疾病的一部分，也可能是其表现特征。最近在小脑共济失调、神经病、前庭反射消失综合征的 RFC1 基因中发现重复扩展，突出了迟发性隐性疾病的普遍性，这些疾病在历史上被认为会导致早发性疾病。
CMT 是一个不断发展的领域，具有相当大的表型和遗传异质性，深度表型分析仍然是当代 CMT 诊断的基石。
