Division of Neurology, Department of Paediatrics, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1E8, Canada.
Genes (Basel). 2024 Feb 21;15(3):266. doi: 10.3390/genes15030266.
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 , , , , , and . 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.
婴儿痉挛综合征（IESS）是一种严重的发育性癫痫性脑病（DEE），其特征为癫痫痉挛，以及脑电图上出现发育迟缓或停滞和高度失律中的一种或两种。多种病因与 IESS 的发展有关；广义上讲，60%的病例被认为具有结构性、代谢性或感染性，其余的则为遗传性或原因不明。癫痫遗传学是一个不断发展的领域，迄今为止已发现与 IESS 相关的 28 种拷贝数变异和 70 种单基因致病性变异。虽然不全面，但一些最常报道的遗传病因包括 21 三体和基因中的致病性变异，如 、 、 、 、 和 。了解 IESS 的遗传机制可能为更好地了解 IESS 病理生理学并改善该疾病的治疗提供机会。本叙述性综述介绍了我们目前对 IESS 遗传学的理解，重点介绍了 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），以及可用的遗传检测方法及其各自的诊断产量。还探讨了与精准医学和 IESS 治疗中的癫痫遗传学相关的未来机会。
