Myers Kenneth A, Scheffer Ingrid E
Research Institute of the McGill University Health Centre, Division of Child Neurology, Department of Pediatrics, and Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, Quebec H4A 3J1, Canada; email:
Epilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia; email:
Annu Rev Pharmacol Toxicol. 2022 Jan 6;62:641-662. doi: 10.1146/annurev-pharmtox-052120-084449. Epub 2021 Sep 27.
Epilepsy is an etiologically heterogeneous condition; however, genetic factors are thought to play a role in most patients. For those with infantile-onset developmental and epileptic encephalopathy (DEE), a genetic diagnosis is now obtained in more than 50% of patients. There is considerable motivation to utilize these molecular diagnostic data to help guide treatment, as children with DEEs often have drug-resistant seizures as well as developmental impairment related to cerebral epileptiform activity. Precision medicine approaches have the potential to dramatically improve the quality of life for these children and their families. At present, treatment can be targeted for patients with diagnoses in many genetic causes of infantile-onset DEE, including genes encoding sodium or potassium channel subunits, tuberous sclerosis, and congenital metabolic diseases. Precision medicine may refer to more intelligent choices of conventional antiseizure medications, repurposed agents previously used for other indications, novel compounds, enzyme replacement, or gene therapy approaches.
癫痫是一种病因异质性疾病；然而，遗传因素被认为在大多数患者中起作用。对于患有婴儿期起病的发育性和癫痫性脑病（DEE）的患者，目前超过50%的患者已获得基因诊断。利用这些分子诊断数据来指导治疗的动机很强，因为患有DEE的儿童通常有耐药性癫痫发作以及与脑癫痫样活动相关的发育障碍。精准医学方法有可能显著改善这些儿童及其家庭的生活质量。目前，对于许多婴儿期起病的DEE的遗传病因已明确诊断的患者，治疗可以有针对性地进行，这些病因包括编码钠或钾通道亚基的基因、结节性硬化症和先天性代谢疾病。精准医学可能指的是更明智地选择传统抗癫痫药物、先前用于其他适应症的重新利用药物、新型化合物、酶替代或基因治疗方法。
