PDF(Pubmed)
Abstract：
Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored.
摘要：
婴儿癫痫性痉挛综合征（IESS）是一种破坏性的发展性癫痫性脑病（DEE），由癫痫性痉挛组成，以及脑电图上的发育退化或停滞和心律失常中的一种或两种。无数的病因与IESS的发展有关；广泛地说，60%的病例被认为是结构性的，代谢或传染性，其余遗传或原因不明。癫痫遗传学是一个不断发展的领域，迄今为止，已经发现了超过28个拷贝数变异和70个与IESS相关的单基因致病变异。虽然不是详尽的，一些最常报道的遗传病因包括21三体和TSC1，TSC2，CDKL5，ARX，KCNQ2、STXBP1和SCN2A。了解IESS的遗传机制可能为更好地辨别IESS病理生理学和改善这种状况的治疗提供机会。这篇叙述性综述概述了我们目前对IESS遗传学的理解，强调IESS发病机制的动物模型，IESS的遗传病因谱(即，染色体疾病,单基因疾病，三核苷酸重复疾病和线粒体疾病)，以及可用的基因测试方法及其各自的诊断产量。还探索了与IESS治疗中的精准医学和癫痫遗传学相关的未来机会。
