Objective: To analyze the clinical phenotypes of epilepsies in children with GABRB2 variants. Methods: Data of 8 epileptic patients with heterozygous GABRB2 variants were retrospectively collected at the Department of Pediatrics, Peking University First Hospital from April 2016 to December 2018. The clinical, electroencephalographic, neuroimaging characteristics, therapeutic and follow-up were analyzed. Results: Eight patients (4 boys, 4 girls) with heterozygous GABRB2 gene pathogenic variants were enrolled. Eight patients had different GABRB2 variants, among whom 2 patients inherited the variants from either parent, and the other 6 patients had de novo variants. Seven variants were novel. Ages at seizure onset ranged from 1 day to 22 months after birth, and the median age was 6 months. The seizure was first observed within one month of age in 2 patients, 1-6 months in 2 patients, 7-12 months in 2 patients, and beyond 1 year of age in 2 patients. Multiple seizure types were observed, including focal seizures in 6 patients, generalized tonic clonic seizures (GTCS) in 4 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. Developmental delay was present in 6 patients. In 8 patients, Dravet syndrome was diagnosed in 3 patients, febrile seizures plus and West syndrome in 2 patients, respectively, Ohtahara syndrome in 1 patient. Six patients had epilepsy with fever sensitivity, and status epilepticus developed in all these patients. The ages at the last follow-up ranged from 8 months to 11 years, and the follow-up data showed that 5 patients were seizure-free, and 2 patients still had seizures, and 1 patient died of recurrent status epilepticus complicated with fungal infection. Conclusions: Epilepsies associated with GABRB2 variants were characterized by an onset in infancy, and the clinical features were heterogenous in seizure types and severities. Most patients had multiple seizures with fever sensitivity, and status epilepticus was common. Their seizures were easily induced by fever or infection. Additionally, the majority of the patients had varying degrees of developmental delay.
目的： 分析GABRB2基因变异相关癫痫的临床表型特点。 方法： 回顾性研究，以2016年4月至2018年12月北京大学第一医院儿科诊治的8例GABRB2基因变异阳性的癫痫患儿为研究对象，对其临床表现、脑电图、头颅影像学特点、治疗及随访结果进行总结。 结果： 8例均携带不同的GABRB2基因杂合变异，其中2例为遗传性变异，6例为新生变异。7例患儿携带国际未报道的新变异。8例患儿（男4例、女4例）起病年龄为1日龄~22月龄，中位起病年龄为6月龄，其中0~<1月龄2例，1~6月龄2例，7月龄~1岁2例，>1岁2例。癫痫发作类型多样，其中局灶性发作6例，全面强直阵挛发作4例，肌阵挛发作3例，痉挛发作2例。8例患儿中6例有发育落后。8例患儿中，3例为Dravet综合征，2例为热性惊厥附加症，2例为婴儿痉挛症，1例为大田原综合征。6例患儿发作有热敏感特点，且病程中均有癫痫持续状态史。末次随访年龄为8月龄~11岁，其中5例癫痫发作已缓解，2例仍有发作，1例因反复癫痫持续状态合并真菌感染已死亡。 结论： GABRB2基因变异导致的癫痫多数在婴儿期起病，癫痫发作类型多样，表型轻重不一，多数患儿发作有热敏感特点，易发生癫痫持续状态，且有不同程度的发育落后。.
Keywords: Epilepsy; Fever sensitivity; GABRB2; Prognosis.