BACKGROUND The advent of Next Generation Sequencing (NGS) has led to a redefining of the genetic landscape of the epilepsies. Hundreds of single gene epilepsies have been described. Genes associated with epilepsy involve diverse processes. Now a substantial proportion of individuals with epilepsy can receive a high definition molecular genetic diagnosis. METHODS In this review we update the current genetic landscape of the epilepsies and categorise the major functional groupings of epilepsy-associated genes. We describe currently available genetic testing approaches. We perform a literature review of NGS studies and review the factors which determine yield in cohorts undergoing testing. We identify factors associated with positive genetic diagnosis and consider the utility of genetic testing in terms of treatment selection as well as more qualitative aspects of care. FINDINGS Epilepsy-associated genes can be grouped into five broad functional categories: ion transport; cell growth and differentiation; regulation of synaptic processes; transport and metabolism of small molecules within and between cells; and regulation of gene transcription and translation. Early onset of seizures, drug-resistance, and developmental comorbidity are associated with higher diagnostic yield. The most commonly implicated genes in NGS studies to date, in order, are SCN1A, KCNQ2, CDKL5, SCN2A, and STXBP1. In unselected infantile cohorts PRRT2, a gene associated with self-limited epilepsy, is frequently implicated. Genetic diagnosis provides utility in terms of treatment choice closing the diagnostic odyssey, avoiding unnecessary further testing, and informing future reproductive decisions. CONCLUSIONS Genetic testing has become a first line test in epilepsy. As techniques improve and understanding advances, its utility is set to increase. Genetic diagnosis, particularly in early onset developmental and epileptic encephalopathies, influences treatment choice in a significant proportion of patients. The realistic prospect of gene therapy is a cause for optimism.

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癫痫和发育障碍：临床中的下一代测序

背景下一代测序（NGS）的出现导致对癫痫遗传图谱的重新定义。已经描述了数百种单基因癫痫。与癫痫相关的基因涉及不同的过程。现在，很大一部分癫痫患者可以接受高清晰度的分子遗传学诊断。方法 在这篇综述中，我们更新了癫痫的当前遗传格局，并对癫痫相关基因的主要功能分组进行了分类。我们描述了目前可用的基因检测方法。我们对 NGS 研究进行了文献回顾，并回顾了决定接受测试队列产量的因素。我们确定与阳性基因诊断相关的因素，并考虑基因检测在治疗选择和护理质量方面的效用。发现 癫痫相关基因可分为五个大的功能类别：离子转运；细胞生长和分化；突触过程的调节；细胞内和细胞间小分子的运输和代谢；以及基因转录和翻译的调控。癫痫发作的早期、耐药性和发育合并症与更高的诊断率相关。迄今为止，NGS 研究中最常涉及的基因依次是 SCN1A、KCNQ2、CDKL5、SCN2A 和 STXBP1。在未经选择的婴儿队列中，PRRT2 是一种与自限性癫痫相关的基因，经常被牵连。基因诊断在治疗选择方面提供了效用，从而结束了诊断过程，避免了不必要的进一步测试，并为未来的生殖决策提供了信息。结论 基因检测已成为癫痫的一线检测。随着技术的进步和理解的进步，它的实用性将会增加。遗传诊断，尤其是早发性发育性脑病和癫痫性脑病，会影响很大一部分患者的治疗选择。基因治疗的现实前景令人乐观。遗传诊断，尤其是早发性发育性脑病和癫痫性脑病，会影响很大一部分患者的治疗选择。基因治疗的现实前景令人乐观。遗传诊断，尤其是早发性发育性脑病和癫痫性脑病，会影响很大一部分患者的治疗选择。基因治疗的现实前景令人乐观。