[Clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation].

Objective: To summarize the clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation. Methods: The clinical data, gene variation and treatment outcome of 12 children with focal epilepsy caused by GATOR1 complex gene variation admitted to Beijing Children's Hospital Affiliated to Capital Medical University from June 2016 to October 2018 were retrospectively analyzed. Results: There were 7 males and 5 females in 12 cases. The epilepsy onset age was 5.5 (3.0, 12.0) months, and from 11 days to 16 months of age. The epileptic seizure types were all focal motor seizures, and one case combined with epileptic spasms. The frequency of seizures in all patients was more than one time per day. Seven cases had frontal lobe epilepsy and two cases had lateral temporal lobe epilepsy. One case had a family history of febrile seizures and two had a family history of suspicious epilepsy. Epileptic form discharges were observed in 9 patients during the interictal phase by electroencephalograms (EEG), and all of them were focal discharges. Eight cases had clinical seizures detected by EEG, in 4 of whom the seizures were originated in frontal region. There were no abnormalities in brain magnetic resonance imaging in 11 cases whereas 1 case had malformation of cortical development of left frontal lobe. Eight patients had DEPDC5 gene variation, one had NPRL2 gene variation, three had NPRL3 gene variation. One case had de novo variation and the other 11 had hereditary variation. There were 11 types of gene variation, including 5 nonsense variations, 3 missense variations, 2 frame shift variations and 1 in frame deletion variation. There was no clear relationship between the clinical phenotype and the genotype. During the follow-up period from 6 months to 2 years and 6 months, 6 cases had seizure control, 3 of them were controlled by oxcarbazepine. The other 6 cases had drug-refractory epilepsy, 2 of them failed with vagus nerve stimulation and ketogenic dietary therapy as well, meanwhile combined with mental retardation. Conclusions: GATOR1 complex gene variation can lead to genetic focal epilepsy, which usually has early onset with frequent seizures. Most of the patients have focal epileptic form discharges on EEG, and there is usually no structural lesion in brain imaging. Most of the patients have hereditary loss-of-function variations. Approximately half of cases are drug-resistant epilepsy.目的： 总结GATOR1复合物基因变异所致儿童局灶性癫痫的临床特征及遗传学特点。 方法： 回顾性总结首都医科大学附属北京儿童医院2016年6月至2018年10月收治的12例GATOR1复合物基因变异所致局灶性癫痫患儿的临床资料，分析其基因变异及治疗转归。 结果： 12例患儿中男7例、女5例，起病年龄为5.5（3.0，12.0）月龄，范围11日龄至16月龄。癫痫发作类型均为局灶性运动性发作，1例合并痉挛发作，发作频率均超过1次/d。7例为额叶癫痫，2例为外侧颞叶癫痫。1例有热性惊厥家族史，2例有可疑癫痫家族史。9例患儿脑电图发作间期可见痫性放电，且均为局灶性；8例脑电图监测到发作，其中4例起始于一侧额区。11例患儿头颅磁共振成像未见异常，1例为左额皮质发育畸形。8例患儿为DEPDC5基因变异，1例为NPRL2基因变异，3例为NPRL3基因变异；1例为新生变异，11例为遗传性变异。共11种基因变异类型，分别为无义变异5种、错义变异3种、移码变异2种、整码缺失1种。患儿临床表型与基因变异的类型、来源无明确关系。随访6个月至2年6个月，6例发作控制，其中3例加用奥卡西平后控制；另6例为药物难治性癫痫，其中2例分别联合迷走神经刺激及生酮饮食治疗亦未能控制发作，合并精神发育迟滞。 结论： GATOR1复合物基因变异可导致遗传性局灶性癫痫，通常起病早，发作频繁，脑电图多为局灶性痫样放电，而影像学常无结构性病灶，多数患儿为遗传性功能丧失性变异，约半数呈药物难治性癫痫。.