Mao Dan-Dan, Li Si-Xiu, Hu Wen-Guang, Chen Hui
Department of Pediatric Neurology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Transl Pediatr. 2025 Jul 31;14(7):1717-1725. doi: 10.21037/tp-2025-157. Epub 2025 Jul 22.
Epilepsy is a prevalent chronic neurological disorder that affects individuals across all age groups. Genetic factors are believed to play a significant role in the etiology of epilepsy; however, epilepsy associated with mutations in the chloride voltage-gated channel 4 () gene is clinically rare.
We report a 2-year and 4-month-old male patient who experienced cluster convulsions due to a heterozygous variant in the gene (NM_001830: c.1024G>A, p. Gly342Arg). This patient exhibited focal seizures with impaired consciousness, which responded well to treatment with valproate and lamotrigine, although he presented with mild intellectual disability (ID) and language deficits.
A review of the existing literature identified only 60 cases, demonstrating a wide phenotypic spectrum. ID of varying degrees is observed in the majority of patients. Seizures typically commence in infancy and early childhood and manifest as multiple types, with focal seizures and generalized tonic-clonic seizures being the most common. Notably, missense variants may lead to a more severe phenotype compared to frameshift variants, and the p. Pro369Leu variant may represent a potential hotspot within the gene. Nearly half of the patients exhibit refractory seizures despite treatment with multiple medications, while valproate, levetiracetam, and lamotrigine are considered viable therapeutic options.
癫痫是一种普遍存在的慢性神经系统疾病，影响所有年龄组的个体。遗传因素被认为在癫痫的病因中起重要作用；然而，与氯离子电压门控通道4（）基因突变相关的癫痫在临床上较为罕见。
我们报告了一名2岁4个月大的男性患者，由于该基因（NM_001830：c.1024G>A，p.Gly342Arg）中的杂合变异而经历了丛集性惊厥。该患者表现为伴有意识障碍的局灶性癫痫发作，对丙戊酸盐和拉莫三嗪治疗反应良好，尽管他存在轻度智力障碍（ID）和语言缺陷。
对现有文献的回顾仅发现60例病例，显示出广泛的表型谱。大多数患者观察到不同程度的ID。癫痫发作通常始于婴儿期和幼儿期，表现为多种类型，局灶性癫痫发作和全身强直阵挛性癫痫发作最为常见。值得注意的是，与移码变异相比，错义变异可能导致更严重的表型，并且p.Pro369Leu变异可能代表该基因内的一个潜在热点。尽管使用多种药物治疗，近一半的患者仍表现为难治性癫痫发作，而丙戊酸盐、左乙拉西坦和拉莫三嗪被认为是可行的治疗选择。
