CAJ | 학술논문

目的：探讨早发性癫痫脑病男性患儿ARX基因突变及其临床表型特点。方法收集42例男性早发性癫痫脑病患儿详细的临床资料，采集患儿及家长外周血，应用PCR、直接测序和多重连接依赖的探针扩增（ MLPA）技术对ARX基因第二外显子进行突变分析。对患儿的临床表型特点进行分析。结果42例早发性癫痫脑病患儿中3例患儿存在ARX基因第二外显子大片段缺失，检出率为7．14％（3/42）。其中1例为非特异性癫痫脑病，2例为婴儿痉挛症。3例患儿均于出生后6个月内出现难以控制的癫痫发作，2例患儿在脑电监测中发现高度失律，3例患儿对多种抗癫痫手段反应差，且均表现为严重的智力运动发育落后或倒退。未检出缺失的39例患儿发作形式呈现更多样化的特点，其中5例患儿大运动发育基本正常，3例患儿对ACTH或生酮饮食手段控制癫痫有效。结论早发性癫痫脑病患儿中部分存在ARX基因第二外显子大片段缺失。具有ARX基因突变的早发性癫痫脑病患儿，其临床表现为6个月内出现难治性癫痫发作，以部分性发作及痉挛发作为主，同时有显著的智力运动发育落后、甚至倒退；少数未检出缺失的患儿的大运动发育可基本正常，对ACTH或生酮饮食反应良好。
목적：탐토조발성전간뇌병남성환인ARX기인돌변급기림상표형특점。방법수집42례남성조발성전간뇌병환인상세적림상자료，채집환인급가장외주혈，응용PCR、직접측서화다중련접의뢰적탐침확증（ MLPA）기술대ARX기인제이외현자진행돌변분석。대환인적림상표형특점진행분석。결과42례조발성전간뇌병환인중3례환인존재ARX기인제이외현자대편단결실，검출솔위7．14％（3/42）。기중1례위비특이성전간뇌병，2례위영인경련증。3례환인균우출생후6개월내출현난이공제적전간발작，2례환인재뇌전감측중발현고도실률，3례환인대다충항전간수단반응차，차균표현위엄중적지력운동발육락후혹도퇴。미검출결실적39례환인발작형식정현경다양화적특점，기중5례환인대운동발육기본정상，3례환인대ACTH혹생동음식수단공제전간유효。결론조발성전간뇌병환인중부분존재ARX기인제이외현자대편단결실。구유ARX기인돌변적조발성전간뇌병환인，기림상표현위6개월내출현난치성전간발작，이부분성발작급경련발작위주，동시유현저적지력운동발육락후、심지도퇴；소수미검출결실적환인적대운동발육가기본정상，대ACTH혹생동음식반응량호。
Objective To explore the ARX gene mutation and clinical phenotypic characteristics in male patients with early-onset epileptic encephalopathy .Methods Detailed clinical information and the peripheral blood of 42 male children with early-onset epileptic encephalopathies and their parents were collected .Exon 2 of ARX gene mutation was screened u-sing PCR-DNA sequencing and multiple ligation-dependent probe amplification ( MLPA) , and the clinical phenotypic char-acteristics were also analyzed .Results Among 42 cases, large deletions of exon 2 for ARX gene can be detected in 3 ca-ses, and the overall mutation rate was 7.14%(3/42).One of the 3 patients was diagnosed as non-specific epileptic en-cephalopathies , the other two were diagnosed as infantile spasm;all 3 patients were attacked by intractable seizures occur-ring in the first six months of life .Two patients presented hypsarrhythmia in the EEG records .All 3 patients were resistant to multiple AEDs and presented severe psychomotor developmental delay or regression .Various seizure types were observed in 39 patients without large deletions of exon 2 for ARX;among them, 5 patients acquired nearly normal gross motor devel-opment, ACTH and ketogenic diet were effective for controlling seizures in 3 patients.Conclusions A part of children with early-onset epileptic encephalopathy have large deletion of exon 2 in ARX gene.Early-onset epileptic encephalopathy children with large deletion of exon 2 in ARX gene present intractable seizures during six months of life , partial seizures and spasms are the most common seizure types .Meanwhile , they are characterized by severe psychomotor developmental delay even regression .Few patients without deletions could acquire nearly normal developmental milestones and respond well to ACTH or ketogenic diet .