3例KCNQ2发育性癫痫性脑病患儿的临床特征及基因变异分析

Clinical Features and Genetic Variation Analysis of Three Children with KCNQ2-Related Developmental and Epileptic Encephalopathy

摘要: 目的：探讨KCNQ2发育性癫痫性脑病患儿的临床特征及基因变异特点，为该疾病的临床诊断与预后评估提供参考。方法：回顾性分析3例确诊为KCNQ2发育性癫痫性脑病患儿的临床病例资料，并系统复习国内外相关文献，总结疾病的临床特征与基因变异特点。结果：3例患儿中，2例为女性，分别于生后24小时内、26小时起病；1例为男性，于生后第3天起病。所有患儿均以癫痫发作为首发症状，发作形式包括间断发作或丛集性发作，发作频繁时频率可达10次/天以上，具体发作类型以局灶性发作为主，部分合并强直发作。脑电图检查显示，3例患儿均存在脑电图异常，表现为多灶性放电、爆发–抑制或高度失节律。治疗方面，初期给予多种抗癫痫发作药物(如苯巴比妥、左乙拉西坦等)治疗，效果均不佳；其中2例患儿在添加奥卡西平后，癫痫发作完全消失。预后方面，3例患儿均出现明显的精神运动发育落后；1例因持续频繁癫痫发作，于1岁6个月时夭折。基因检测结果显示，3例患儿均携带KCNQ2基因新发错义变异，具体变异位点分别为c.620G>C (p.Arg207Pro)、c.997C>T (p.Arg333Trp)及c.908C>T (p.Ser303Phe)。结论：KCNQ2基因特定位点的新发错义变异是导致发育性癫痫性脑病的重要致病原因。由该类变异引发的疾病具有典型临床特征：癫痫多在新生儿早期起病，发作频率高且对多种抗癫痫药物反应差，常合并明显精神运动发育迟缓，整体预后差。

Abstract: Objective: To explore the clinical features and genetic variation characteristics in children with KCNQ2-related developmental and epileptic encephalopathy (DEE), and to provide references for the clinical diagnosis and prognostic evaluation of this disease. Methods: A retrospective analysis was performed on the clinical case data of three children diagnosed with KCNQ2-related developmental and epileptic encephalopathy (DEE). Additionally, relevant domestic and international literature was systematically reviewed to summarize the clinical features and genetic variation characteristics of the disease. Results: Among the three children, two were female, with onset within 24 hours and 26 hours after birth; one was male, with onset on the third day after birth. All children presented with epileptic seizures as the initial symptom, with seizure patterns including intermittent seizures or clustered seizures. When seizures were frequent, the frequency could reach more than 10 episodes per day. The specific seizure types were mainly focal seizures, and some were complicated with tonic seizures. Electroencephalogram (EEG) examination showed that all three children had abnormal electroencephalographic activity, manifested as multifocal discharges, burst-suppression waves, or hypsarrhythmia. In terms of treatment, multiple anti-seizure medications (such as phenobarbital, levetiracetam, etc.) were administered initially, but the therapeutic effect was poor in all cases; epileptic seizures disappeared completely in two children after oxcarbazepine was added. Regarding prognosis, all three children had significant psychomotor developmental delay; one child died at 1 year and 6 months of age due to persistent and frequent epileptic seizures. Genetic testing results revealed that all three children carried de novo missense variants in the KCNQ2 gene, with specific variant sites being c.620G>C (p.Arg207Pro), c.997C>T (p.Arg333Trp), and c.908C>T (p.Ser303Phe). Conclusion: De novo missense variants at specific loci of the KCNQ2 gene are important pathogenic causes of developmental and epileptic encephalopathy (DEE). Diseases caused by such variants exhibit typical clinical features: epilepsy usually onsets in the early neonatal period, with high seizure frequency and poor response to multiple anti-seizure medications; they are often accompanied by significant psychomotor developmental delay, resulting in an overall poor prognosis.