From Genetic Testing to Precision Medicine in Epilepsy
From Genetic Testing to Precision Medicine in Epilepsy
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DOI：
10.1007/s13311-020-00835-4
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发表时间：
2020-01-24
影响因子：
5.7
通讯作者：
Minassian, Berge A.
中科院分区：
文献类型：
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作者：
Striano, Pasquale;Minassian, Berge A.
癫痫包括许多以反复发作为共同特征的疾病。大量不同的综合征和发作类型以及对治疗的高度可变的个体间反应使得这种情况的管理往往具有挑战性。在过去的二十年中，半数以上的癫痫都有遗传病因，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有关，包括一些局灶性和病变型以及特定的癫痫发育性脑病。目前已有几种基因检测方法，包括有针对性的检测，以及革命性的工具，这些工具使得对人类基因组的所有编码（全外显子组）和非编码（全基因组）区域进行测序成为可能。这些最近的技术进步也推动了癫痫基因的发现，增加了我们对许多癫痫疾病分子机制的理解，最终为某些综合征（如Dravet综合征、pyroxidine依赖性癫痫和葡萄糖转运蛋白1缺乏症）的精准医学提供了靶点。然而，这些例子只代表了所有类型癫痫中相对较小的一部分，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，如神经发育和神经精神合并症，尚未有可能解决。我们在此总结了基因检测的最新进展，并为一些癫痫疾病的正确检测选择提供了最新的方法，并为一些单基因癫痫提供了量身定制的治疗方法。在接下来的几年里，最可能的情况是癫痫治疗将与目前几乎是经验主义的方法大不相同，最终将出现一种大规模适用的“精准医学”方法。
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.