Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Oxford OX3 9DS, UK.
Int J Mol Sci. 2018 Jun 5;19(6):1677. doi: 10.3390/ijms19061677.
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 and , impairing the synthesis and recycling of acetylcholine, have recently been described. In addition, a novel group of CMS due to mutations in , , , and 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 mutations can cause CMS, thus bridging myasthenic disorders with dystroglycanopathies. Finally, the discovery of 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.
先天性肌无力综合征（CMS）是一种以神经肌肉传递障碍为特征的遗传性疾病。本综述概述了 CMS，并强调了该领域的最新进展，包括新的 CMS 致病基因和改进的治疗策略。最近描述了由于 和 基因突变导致的 CMS，这些突变会损害乙酰胆碱的合成和再循环。此外，还鉴定了一组新的 CMS，其病因是编码与突触小泡胞吐作用相关分子的 、 、 和 基因突变。越来越多的表现出中枢神经系统表现以及神经肌肉无力的突触前 CMS 表明，肌无力可能只是更广泛疾病表型的一小部分。此外，随着报告表明 突变可导致 CMS，糖基化异常的范围已增加，从而将肌无力障碍与 dystroglycanopathies 联系起来。最后，发现 突变和层粘连蛋白 α5 缺乏症有助于引起对细胞外基质蛋白在肌肉终板形成和维持中的作用的关注。越来越多的报道表明，β2-肾上腺素能激动剂单独或与吡啶斯的明或 3,4-Dyaminopiridine 联合使用，对包括 AChR 缺乏和糖基化异常在内的不同 CMS 亚型均有效，从而扩大了现有治疗方法的范围。
