Peng Bingwei, Zhu Haixia, Tian Yang, Li Xiaojing, Wang Xiuying, Gao Yuanyuan, Zhang Yani, Shen Huiling, Chen Wenxiong
Department of Neurology, Women and Children's Medical Center affiliated to Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Apr 10;41(4):426-431. doi: 10.3760/cma.j.cn511374-20230421-00227.
To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE).
Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children's Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed.
Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c.677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group (P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures.
The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.
探讨46例与SCN1A相关的发育性癫痫性脑病（DEE）患儿的临床表型与基因型之间的相关性。
收集2018年1月至2022年6月在广州妇女儿童医疗中心确诊为DEE且存在SCN1A变异的46例患儿的临床资料。根据发病年龄、临床表现、神经发育状况及基因检测结果对患儿进行分组，分析SCN1A基因型与临床表型之间的相关性。
46例患者中，2例（4.35%）在3个月龄前出现症状，42例（91.30%）在3至9个月龄，2例（4.35%）在10个月龄后。2例（4.35%）表现为婴儿期迁移性局灶性癫痫发作（EIMFS），44例（95.7%）表现为Dravet综合征（DS），其中28例（63.6%）为局灶性发作（DS-F），13例（29.5%）为肌阵挛型（DS-M），1例（2.27%）为全身性发作（DS-G），2例（4.55%）为癫痫持续状态型（DS-SE）。2例EIMFS患儿均有严重发育迟缓，DS患者中7例发育正常，其余有发育迟缓。通过基因测序共鉴定出44个变异，其中包括16个错义变异和28个截短变异。所有EIMFS患儿均携带c.677C>T（p.Thr226Met）错义变异。在DS组中，错义变异组与截短变异组的发病年龄有显著差异（P<0.05）。错义变异在D1区（7/15，46.7%）和孔区（8/15，53.3%）更常见，而截短变异在D1区更常见（12/28，42.9%）。孔区以外有变异的患儿更易发生肌阵挛发作。
DEE的临床表型多样。SCN1A基因截短变异与错义变异个体的发病年龄存在差异。孔区以外的错义变异与肌阵挛发作的较高发生率相关。
