KCNT2基因变异致遗传性癫痫伴热性惊厥附加症一家系分析并文献复习  

Analysis of a family with inherited generalized epilepsy with febrile seizures plus caused by the KCNT2 mutation and literature review

作　　者：田杨 李小晶 王秀英 曾意茹 侯池 彭炳蔚 陈文雄 梁惠慈 Tian Yang;Li Xiaojing;Wang Xiuying;Zeng Yiru;Hou Chi;Peng Bingwei;Chen Wenxiong;Liang Huici(Department of Pediatric Neurology,Guangzhou Women and Children′s Medical Center,Guangzhou 510000,China)

机构地区：[1]广州市妇女儿童医疗中心神经内科,510000

出　　处：《中华实用儿科临床杂志》2021年第2期136-139,共4页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的总结KCNT2基因突变所致遗传性癫痫伴热性惊厥附加症(GEFS+)一家系的临床特点及治疗情况,并进行文献复习。方法收集2019年5月在广州市妇女儿童医疗中心神经内科就诊的GEFS+患儿及其家族成员的临床资料;提取患儿及其父母、哥哥、外祖父母的外周血DNA,采用癫痫疾病靶向测序进行遗传学分析及验证。以"KCNT2"基因为关键词检索PubMed数据库、中国期刊全文数据库和万方医学文献数据库建库至2019年8月相关文献,并进行总结。结果先证者,男,3岁,因"频繁抽搐5个月"入院,表现为双眼凝视伴四肢节律性抖动(肌阵挛-痉挛样),每日有3~8次发作,2岁时有发热性惊厥3次。先后予丙戊酸钠、托吡酯、硝西泮、左乙拉西坦口服仍有抽搐;哥哥、母亲儿时有高热惊厥史,家系其他成员无惊厥史。发作期脑电图为广泛性1 Hz高波幅棘慢波发放。先证者、哥哥及母亲、外祖母检测到KCNT2基因c.574C>T(p.Q192X)(杂合)同一无义突变,既往未见报道,家系余成员KCNT2基因c.574位点未见该变异。文献检索中文文献0篇,病历资料齐全的外文文献2篇共3例散发患儿,加上本家系4例共7例患者涉及4个突变位点,其中错义突变3个,无义突变1个。3例散发患儿临床表现为婴幼儿早期癫痫性脑病,本研究家系表现为热性惊厥和热性惊厥附加症。结论在GEFS+患儿中发现了KCNT2基因尚未见报道的突变和表型,扩大了基因突变谱,为家系遗传咨询提供了基础;KCNT2基因突变所致GEFS+可能对抗癫痫药物不敏感。Objective To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus(GEFS+)caused by the KCNT2 gene mutation and review the literature.Methods Clinical data of a child with GEFS+and his family members who visited Department of Pediatric Neurology,Guangzhou Women and Children′s Medical Center in May 2019 were collected.DNA samples were collected from the peripheral blood of the proband,his parents,his elder brother,and his maternal grandparents,and genetic analysis and verification were performed using the next-generation sequencing technique.Using"KCNT2"as the key word,literature was retrieved from PubMed,China National Knowledge Infrastructure and Wanfang databases(up to August 2019).Results The proband was a 3-year-old boy who was admitted to Guangzhou Women and Children′s Medical Center because of frequent epileptic seizures in the past 5 months.He presented with a binocular gaze and experienced 3 to 8 times of extremities myoclonic-spastic epileptic attacks every day.He had a history of 3 times of febrile seizures at the age of 2 years old.His seizures were refractory to Sodium valproate,Topiramate,Nitrazepam and Levetiracetam.His elder brother and mother had a history of childhood febrile seizures.Other members in the family had no history of convulsion.Ictal electroencephalogram showed general 1 Hz high voltage spike-slow waves.A heterozygous nonsense mutation of KCNT2 gene c.574C>T(p.Q192X)that was never reported previously was detected in the proband,his brother,mother and maternal grandmother.Furthermore,no other family members carried the mutation at the c.574 locus of the KCNT2 gene.No article in Chinese was found,and 2 articles in a language other than Chinese provided the complete data of 3 sporadic cases.Together with 4 cases in the family studied in this article,there were 7 cases and 4 mutation sites in KCNT2 gene.Of these mutations,there were 3 missense mutations and 1 nonsense mutation.Three sporadic patients presented wit

关 键 词：突变 癫痫 惊厥 发热性 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R720.597[医药卫生—临床医学]