Identifying the optimal treatment based on specific characteristics of each patient is the main promise of precision medicine. In the field of epilepsy, the identification of more than 100 causative genes provides the enticing possibility of treatments targeted to specific disease etiologies. These conditions include classical examples, such as the use of vitamin B6 in antiquitin deficiency or the ketogenic diet in GLUT1 deficiency, where the disease mechanism can be directly addressed by the selection of a specific therapeutic compound. For epilepsies caused by channelopathies there have been advances in understanding how the selection of existing medications can be targeted to the functional consequences of genetic alterations. We discuss the examples of the use of sodium channel blockers such as phenytoin and oxcarbazepine in the sodium channelopathies, quinidine in KCNT1-related epilepsies, and strategies in GRIN-related epilepsies as examples of epilepsy precision medicine. Assessing the clinical response to targeted treatments of these conditions has been complicated by genetic and phenotypic heterogeneity, as well as by various neurological and non-neurological comorbidities. Moving forward, the development of standardized outcome measures will be critical to successful precision medicine trials in complex and heterogeneous disorders like the epilepsies. Finally, we address new frontiers in epilepsy precision medicine, including the need to match the growing volume of genetic data with high-throughput functional assays to assess the functional consequences of genetic variants and the ability to extract clinical data at large scale from electronic medical records and apply quantitative methods based on standardized phenotyping language.

中文翻译：

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基因癫痫的个性化医学-可能性，挑战和新领域。

根据每个患者的具体特征确定最佳治疗方法是精准医学的主要前景。在癫痫领域，对100多个致病基因的鉴定为针对特定疾病病因的治疗提供了诱人的可能性。这些疾病包括经典的例子，例如在抗泛素缺乏症中使用维生素B6或在GLUT1缺乏症中使用生酮饮食，这些疾病的发病机理可以通过选择特定的治疗性化合物来直接解决。对于由通道病引起的癫痫病，在了解如何将现有药物的选择针对基因改变的功能后果方面取得了进展。我们讨论在钠通道病中使用苯妥英钠和奥卡西平等钠通道阻滞剂，在KCNT1相关癫痫中使用奎尼丁和在GRIN相关癫痫中使用策略作为癫痫精密药物的示例。遗传和表型异质性以及各种神经系统和非神经系统合并症使评估针对这些疾病的靶向治疗的临床反应变得复杂。展望未来，标准化结果测量的发展对于在复杂和异质性疾病（如癫痫病）中成功进行精密医学试验至关重要。最后，我们探讨了癫痫精密医学的新领域，