Epilepsy includes a number of medical conditions with recurrent seizures as common denominator. The large number of different syndromes and seizure types as well as the highly variable inter-individual response to the therapies makes management of this condition often challenging. In the last two decades, a genetic etiology has been revealed in more than half of all epilepsies and single gene defects in ion channels or neurotransmitter receptors have been associated with most inherited forms of epilepsy, including some focal and lesional forms as well as specific epileptic developmental encephalopathies. Several genetic tests are now available, including targeted assays up to revolutionary tools that have made sequencing of all coding (whole exome) and non-coding (whole genome) regions of the human genome possible. These recent technological advances have also driven genetic discovery in epilepsy and increased our understanding of the molecular mechanisms of many epileptic disorders, eventually providing targets for precision medicine in some syndromes, such as Dravet syndrome, pyroxidine-dependent epilepsy, and glucose transporter 1 deficiency. However, these examples represent a relatively small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure control, and other clinical aspects, such as neurodevelopmental and neuropsychiatric comorbidities, have yet been possible to address. We herein summarize the most recent advances in genetic testing and provide up-to-date approaches for the choice of the correct test for some epileptic disorders and tailored treatments that are already applicable in some monogenic epilepsies. In the next years, the most probably scenario is that epilepsy treatment will be very different from the currently almost empirical approach, eventually with a “precision medicine” approach applicable on a large scale.

中文翻译：

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从基因检测到癫痫精准医学。


癫痫包括许多以反复发作为共同点的医疗状况。大量不同的综合征和癫痫类型以及个体间对治疗的反应差异很大，使得这种疾病的治疗往往具有挑战性。在过去的二十年中，超过一半的癫痫症都揭示了遗传病因，离子通道或神经递质受体的单基因缺陷与大多数遗传性癫痫形式有关，包括一些局灶性和病变形式以及特定的癫痫症发育性脑病。现在有多种基因测试可供使用，包括靶向测定和革命性工具，这些工具使人类基因组的所有编码（全外显子组）和非编码（全基因组）区域的测序成为可能。这些最新的技术进步也推动了癫痫的基因发现，并增加了我们对许多癫痫疾病的分子机制的理解，最终为某些综合征的精准医学提供了靶标，例如 Dravet 综合征、吡啶依赖性癫痫和葡萄糖转运蛋白 1 缺乏症。然而，这些例子代表了所有类型癫痫的相对较小的子集，迄今为止，癫痫的精准医学主要集中在癫痫发作控制上，而其他临床方面，例如神经发育和神经精神合并症，尚有可能得到解决。我们在此总结了基因检测的最新进展，并提供了为某些癫痫疾病选择正确检测的最新方法以及已经适用于某些单基因癫痫的定制治疗方法。 未来几年，最有可能的情况是，癫痫治疗将与目前几乎是经验性的方法有很大不同，最终采用大规模适用的“精准医学”方法。