Shandong Second Medical University, Weifang, China.
Linyi People's Hospital, Linyi, China.
Epilepsia Open. 2024 Oct;9(5):1658-1669. doi: 10.1002/epi4.13028. Epub 2024 Aug 14.
To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2-related epilepsy.
A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next-generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations.
We identified 23 KCNQ2 gene mutations. 73.9% (n = 17) of the mutation sites were located in S5-S6 segments and the C-terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video-electro-encephalography, three cases with self-limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2-DEE. At the final follow-up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2-DEE had mild to severe developmental backwardness.
Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2-related epilepsy. The gene mutation sites are mostly located in S5-S6 segments and the C-terminal region, and the former is usually associated with KCNQ2-DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2-DEE. Some cases with KCNQ2-related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2-DEE.
This article reports 23 cases of children with KCNQ2-related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2-related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2-related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.
总结中国儿童 KCNQ2 相关性癫痫的临床特征和基因突变特征。
对 2017 年 1 月至 2023 年 12 月在临沂市人民医院就诊的遗传性癫痫患儿进行队列评估。经下一代测序和致病性分析后，我们总结了 KCNQ2 基因突变患儿的病历和基因检测数据。
共发现 23 种 KCNQ2 基因突变。73.9%（n=17）的突变位点位于 S5-S6 段和 C 末端区域。除了常见的表型外，还发现了 2 种新的表型：婴儿痉挛伴阵发性舞蹈手足徐动症（ICCA）和热性惊厥附加症（FS+）。所有视频脑电图异常的病例中，3 例自限性家族性婴儿癫痫（SeLNE）表现为少量多灶性放电。在使用特定抗癫痫药物的患者中，药物反应的患者数量统计如下：奥卡西平（8/9，88.9%）、左乙拉西坦（5/7，71.4%）、苯巴比妥（9/16，56.3%）和托吡酯（2/5，40.0%）。然而，苯巴比妥治疗 SeLNE 和 KCNQ2-DEE 的疗效差异很大。在最终随访时，1 例 SeLNE 患儿出现短暂发育倒退，7 例 KCNQ2-DEE 患儿出现轻度至重度发育落后。
尽管在临床上很少见，但我们报告了 10 种新的 KCNQ2 突变和两种新的表型：ICCA 和 FS+。这进一步扩展了 KCNQ2 相关性癫痫的遗传和表型谱。基因突变位点多位于 S5-S6 段和 C 末端区域，前者常与 KCNQ2-DEE 相关。对于 KCNQ2-DEE，应优先选择钠离子通道阻滞剂（包括奥卡西平和托吡酯）和左乙拉西坦，而非苯巴比妥。一些 KCNQ2 相关性癫痫患儿在频繁发作期间可能出现短暂的发育倒退。早期治疗和早期控制癫痫发作可能有利于 KCNQ2-DEE 患儿获得良好的预后。
