MDUK Neuromuscular centre, Children's Hospital, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Neurosciences Group, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
Neuromuscul Disord. 2021 Oct;31(10):943-954. doi: 10.1016/j.nmd.2021.07.400.
Congenital myasthenia syndromes are rare but often treatable conditions affecting neuromuscular transmission. They result from loss or impaired function of one of a number of proteins secondary to a genetic defect. An estimate of the prevalence in the UK gave 9.2 cases per million, however, this is likely an underestimate since the adoption of next generation sequencing for diagnosis away from specialist centres is enhancing the 'pick up' rate. Next generation sequencing has helped identify a series of novel genes that harbour mutations causative for congenital myasthenic syndrome that include not only genes that encode proteins specifically expressed at the neuromuscular junction but also those that are ubiquitously expressed. The list of genes harbouring disease-causing mutations for congenital myasthenic syndrome continues to expand and is now over 30, but with many of the newly identified genes it is increasingly being recognised that abnormal neuromuscular transmission is only one component of a multifaceted phenotype in which muscle, the central nervous system, and other organs may also be affected. Treatment can be tailored to the underlying molecular mechanism for impaired neuromuscular transmission but treating the more complex multifaceted disorders and will require development of new therapies.
先天性肌无力综合征较为罕见，但常影响神经肌肉传递，可治疗。这些疾病由多种蛋白缺失或功能障碍引起，而蛋白功能障碍继发于遗传缺陷。英国对该病的患病率进行了评估，结果为每百万 9.2 例，但由于采用下一代测序技术对远离专业中心的患者进行诊断，患病率可能被低估。下一代测序技术有助于鉴定一系列导致先天性肌无力综合征的新基因，这些基因不仅包括在神经肌肉接头特异性表达的蛋白编码基因，还包括广泛表达的基因。携带先天性肌无力综合征致病突变的基因列表仍在不断扩大，现已超过 30 个，但对于许多新发现的基因，人们越来越认识到异常的神经肌肉传递仅是多方面表型的一个组成部分，肌肉、中枢神经系统和其他器官也可能受到影响。可根据神经肌肉传递障碍的潜在分子机制进行治疗，但更复杂的多方面疾病的治疗需要开发新疗法。
