Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Neurology, Great Ormond Street Hospital for Children, London, United Kingdom.
Austin Health and Royal Children's Hospital, Florey and Murdoch Children's Research Institutes, University of Melbourne, Melbourne, VIC, Australia.
Handb Clin Neurol. 2024;203:157-184. doi: 10.1016/B978-0-323-90820-7.00016-1.
Recent advances in genetic diagnosis have revealed the underlying etiology of many epilepsies and have identified pathogenic, causative variants in numerous ion and ligand-gated channel genes. This chapter describes the clinical presentations of epilepsy associated with different channelopathies including classic electroclinical syndromes and emerging gene-specific phenotypes. Also discussed are the archetypal epilepsy channelopathy, SCN1A-Dravet syndrome, considering the expanding phenotype. Clinical presentations where a channelopathy is suspected, such as sleep-related hypermotor epilepsy and epilepsy in association with movement disorders, are reviewed. Channelopathies pose an intriguing problem for the development of gene therapies. Design of targeted therapies requires physiologic insights into the often multifaceted impact of a pathogenic variant, coupled with an understanding of the phenotypic spectrum of a gene. As gene-specific novel therapies come online for the channelopathies, it is essential that clinicians are able to recognize epilepsy phenotypes likely to be due to channelopathy and institute early genetic testing in both children and adults. These findings are likely to have immediate management implications and to inform prognostic and reproductive counseling.
遗传诊断的最新进展揭示了许多癫痫的潜在病因，并在许多离子和配体门控通道基因中发现了致病性、因果变异体。本章描述了与不同通道病相关的癫痫的临床表现，包括经典的电临床综合征和新兴的基因特异性表型。还讨论了癫痫通道病的典型代表 SCN1A-Dravet 综合征，考虑到其扩展的表型。对疑似通道病的临床表现，如睡眠相关运动过度性癫痫和与运动障碍相关的癫痫进行了回顾。通道病对基因治疗的发展提出了一个有趣的问题。靶向治疗的设计需要对致病变异体的多方面影响有生理上的认识，同时还需要了解基因的表型谱。随着针对通道病的基因特异性新型疗法的出现，临床医生能够识别可能由通道病引起的癫痫表型，并在儿童和成人中尽早进行基因检测至关重要。这些发现可能具有直接的管理意义，并为预后和生殖咨询提供信息。
