遗传性发育性癫痫性脑病神经生物学及临床诊治研究进展

Advances in the neurobiology and clinical diagnosis and treatment of hereditary developmental epileptic encephalopathies

发育性癫痫性脑病(Developmental epileptic encephalopathies,DEE)是以早发癫痫、脑电图异常及发育落后或倒退为主要特征的一组疾病,具有病因复杂、药物难治的特点,严重影响患儿,尤其是婴幼儿的发育,是儿童神经系统疾病中的难题。近年来,随着精准医学的研究逐渐兴起,已发现越来越多的DEE致病基因,但这些基因在体内具体的致病机制及信号通路依然有待研究。本文主要介绍了DEE遗传模式以及基因检测的选择,通过癫痫表型来辅助判断基因检测的时机,尤其是单基因突变相关的DEE和新的治疗药物,以辅助DEE临床诊疗决策。同时介绍利用用于DEE研究的神经生物学模型来有效推进癫痫研究,从而针对性进行基因靶向治疗。

Developmental epileptic encephalopathies(DEEs)are a group of disorders characterized by early-onset seizures,abnormal electroencephalogram(EEG)patterns,and developmental delay or regression.They are characterized by complex etiology and are often refractory to treatment,severely impacting affected children,particularly infants and toddlers,and pose a challenge in pediatric neurology.In recent years,with the rise of precision medicine,an increasing number of pathogenic genes associated with DEEs have been discovered.However,the specific pathogenic mechanisms and signaling pathways of these genes in the body still require further investigation.This article primarily discusses the genetic patterns of DEEs and the selection of genetic testing,emphasizing the timing of genetic testing assisted by the epilepsy phenotype,especially in DEEs associated with single-gene mutations and new therapeutic drugs,to aid in clinical decision-making for DEEs.It also introduces the use of neurobiological models for DEE research to effectively advance epilepsy research,thereby enabling targeted gene therapy.