不明原因早期癫痫性脑病的遗传基础研究与进展.docx

doi：10.3969 j.issn.1000-3606.2013.06.022·文献综述·不明原因早期癫性脑病的遗传基础研究与进展彭镜综述尹飞审校中南大学湘雅医院儿科 (湖南长沙 410078)摘要： 早期癫 性脑病（early-onset epileptic encephalopathies，EEEs）是指在新生儿期或婴儿期出现持续的癫 性活动，从而导致认知、运动全面发育落后，自闭症等灾难性的神经系统后遗症。近年来的研究提示，基因突变及拷贝数变异（rare copy number variants，CNV）与本病密切相关。文章介绍国际抗癫 联盟（International League Against Epilepsy，ILAE）确认的、但病因不明的6种EEEs遗传研究进展，以及CNVs与EEEs的关系，以提高儿科神经专科医师对病因不明确的EEEs临床表型及基因型的认识。关键词： 早期癫 性脑病； 临床表型；[临床儿科杂志,2013,3１(6)：578-583]基因型A中图分类号： R725文献标志码：文章编号： 1000-3606 (2013) 06-0578-06Genetic contribution to early-onset epileptic encephalopathies Reviewer: PENG Jing, Reviser: YIN Fei (Departmentof Pediatrics, Xiangya Hospital of Central-South University, Changsha 410078, Hunan, China)Abstract: Early-onset epileptic encephalopathies (EEEs) are devastating disorders characterized by progressive psy- chomotor retardation, recurrent clinical seizures or prominent interictal epileptiform discharges during the neonatal and early infantile periods. Recent studies highlighted that half of EEEs have been attributed to copy number variants or genetic mutations. Given the complexity of such evaluations, we summarized recent updates on genetic evaluation of 6 types of epileptic encepha- lopathy which have phenotypic consistence with epilepsy syndrome according to the International League against Epilepsy (ILAE)classifications, and emphasized the role of rare copy number variants in EEEs. The purpose of this review is to improve theknowledge of pediatric neurologists in the evaluation and counseling of patients with etiologically obscure EEEs.(J Clin Pediatr,2013,31(6):578-583)Key words: early-onset epileptic encephalopathies; phenotypes; genotype早期癫 性脑病（early-onset epileptic encephalopathies，EEEs）是指在新生儿期或婴儿期出现持续的癫 性活动（包括临 床频繁的癫 发作以及发作间期脑电持续的 性放电），从而导 致认知、运动全面发育落后，智力低下，自闭症等灾难性的神经系 统后遗症 [1，2]。与成熟脑不同，由于持续的 性活动影响早期发 育中大脑的结构、突触可塑性、神经环路形成，导致大脑结构和功 能发育停滞，所以这些患者常伴有小头畸形、脑萎缩等，且预后不 良 [3]。EEEs 病因复杂。随着现代医学发展，检测手段日益先进， 部分获得性脑损伤、脑结构异常、遗传代谢性疾病的患者通过血 生化检测、头颅影像学检查、代谢病筛查可以获