目的 分析新生儿遗传性癫痫的临床与基因变异特征，探究基因变异特点与临床表现的相关性。方法 回顾性收集2019年1月至2024年12月河北省儿童医院收治的新生儿遗传性癫痫病例，根据基因测序结果分为KCNQ2组和非KCNQ2组，比较两组临床特征，并分析KCNQ2基因型-表型相关性。结果 共纳入新生儿遗传性癫痫43例，男26例、女17例，中位胎龄39.4（38.1~40.3）周，出生体重3 400（3 000~3 400）g，KCNQ2组24例、非KCNQ2组19例。癫痫起病时间为生后3.0（2.0~7.0）d，与非KCNQ2组相比，KCNQ2组癫痫起病时间更早，差异有统计学意义（P<0.05）。发作形式以阵挛（62.8%）、强直（53.5%）发作为主，头颅磁共振成像以脑实质信号异常（72.1%）为主，视频脑电图以多灶性放电（34.9%）多见，KCNQ2组和非KCNQ2组之间差异均无统计学意义（P>0.05）。KCNQ2组自限性新生儿癫痫（SeLNE）13例、发育性癫痫性脑病（DEE）11例，其中23例成功随访，19例发作控制、8例发育迟缓、2例死亡；非KCNQ2组SeLNE 1例、DEE10例、其他8例，其中13例随访成功，7例发作控制、7例发育迟缓、4例死亡。KCNQ2组SeLNE比例高于非KCNQ2组（54.2%对5.3%，P<0.01），死亡和发育迟缓比例低于非KCNQ2组（43.5%对84.6%，P=0.033）。KCNQ2核苷酸序列变异共19例，其中10例SeLNE，5例遗传性变异，4例错义变异，7例氨基酸改变位于C末端。9例DEE均为新发变异，其中7例错义变异，5例氨基酸改变位于S4、S6及邻近区域、B螺旋区。预测11例错义变异蛋白结构变化：4例SeLNE中2例蛋白二级结构改变，3例氢键改变，4例蛋白稳定性下降；7例DEE中6例蛋白二级结构改变，4例氢键改变，6例蛋白稳定性下降。结论 新生儿遗传性癫痫中KCNQ2基因变异最多见。与其他基因变异相比，KCNQ2变异所致新生儿癫痫起病时间更早，不良预后比例较低，其中新发、错义和重要结构域的变异可能与DEE表型相关。

Objective To analyze the clinical and genetic variation characteristics of hereditary epilepsy in neonates and explore the correlation between the characteristics of genetic variations and clinical manifestations. Methods A retrospective collection was made of neonatal hereditary epilepsy cases admitted to Hebei Children's Hospital from January 2019 to December 2024. The cases were divided into KCNQ2 group and non-KCNQ2 group based on the results of gene sequencing. The clinical features of the two groups were compared, and the genotype-phenotype correlation of KCNQ2 was analyzed. Results A total of 43 cases of neonatal hereditary epilepsy were included, including 26 boys and 17 girls, with a gestational age of 39.4 (38.1-40.3) weeks and a birth weight of 3400 (3000-3400) g. There were 24 cases in the KCNQ2 group and 19 cases in the non-KCNQ2 group. The onset time of epilepsy was 3.0 (2.0-7.0) days after birth, which was earlier in the KCNQ2 group than in the non-KCNQ2 group (P<0.05). The main seizure forms were clonic (62.8%) and tonic (53.5%) seizures. The main abnormality on head MRI was abnormal brain parenchymal signal (72.1%). The most common finding on video electroencephalogram was multifocal discharges (34.9%). There were no statistically significant differences between the two groups (P>0.05). In the KCNQ2 group, there were 13 cases of self-limiting neonatal epilepsy (SeLNE) and 11 cases of developmental and epileptic encephalopathy (DEE). Among the 23 cases successfully followed up, 19 cases had seizure control, 8 cases had significant developmental delay, and 2 cases died. In the non-KCNQ2 group, there was 1 case of SeLNE, 10 cases of DEE, and 8 other cases. Among the 13 cases successfully followed up, 7 cases had seizure control, 7 cases had significant developmental delay, and 4 cases died. The proportion of SeLNE in the KCNQ2 group was higher than that in the non-KCNQ2 group (54.2% vs. 5.3%, P<0.01), and the proportion of death and significant developmental delay was lower in the KCNQ2 group (43.5% vs. 84.6%, P=0.033). There were 19 cases of KCNQ2 nucleotide sequence variations, including 10 cases of SeLNE, 5 cases of hereditary variations, and 4 cases of missense variations. Seven amino acid changes were located at the C-terminal. All 9 cases of DEE were de novo variations, including 7 cases of missense variations, and 5 amino acid changes were located at the S4, S6 and adjacent regions, and the B-helix region. Prediction of protein structural changes induced by 11 missense variants: among 4 SeLNE cases, 2 showed alterations in protein secondary structure, 3 exhibited changes in hydrogen bonds, and 4 demonstrated decreased protein stability; among 7 DEE cases, 6 displayed alterations in protein secondary structure, 4 presented changes in hydrogen bonds, and 6 manifested decreased protein stability. Conclusions KCNQ2 gene variations are the most common in neonatal hereditary epilepsy. Compared with other gene variations, KCNQ2-induced neonatal epilepsy has an earlier onset time and a lower proportion of adverse outcomes. Among them, de novo, missense, and variations at important functional domain sites, may be associated with severe phenotypes of DEE.