Syu Yu Min, Lee Inn-Chi, Lu Jyh-Feng, Hung Pi-Lien, Hong Syuan-Yu, Yang Ming-Tao, Liang Jao-Shwann
Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, 22021, Taiwan; Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei, 10449, Taiwan.
Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
Pediatr Neonatol. 2025 May;66(3):223-229. doi: 10.1016/j.pedneo.2024.03.013. Epub 2024 Aug 19.
SCN1A channelopathy is the most well-known cause for epileptic encephalopathies and contributes to a wide phenotypic spectrum. The variable expressivity is troublesome for the interpretation of clinical significance and prognoses. To investigate the clinical manifestations, medications and outcomes of patients with SCN1A channelopathies, we conducted this observation retrospective study in Taiwan.
A cohort consisting of 16 patients (5 males and 11 females) from multiple centers with identified SCN1A variants was investigated and phenotypically relevant factors were recorded. The variants were identified using NGS and confirmed by Sanger sequencing. A panel of 90 epileptic-related genes was used to identify SCN1A variants and to evaluate some of the potential SCN1A modifier genes.
The mean age of seizure onset was 10.4 months. Twelve of the sixteen patients (75%) had different degrees of neurocognitive sequela and psychobehavioral comorbidity in our cohort. Cognitive impairment was noted in all ten patients with Dravet syndrome (DS) and in two of the patients with non-DS phenotypes. A lower response rate to medications was also noted in patients with DS. Notably, a medication-specific tendency towards valproic acid (VPA), clobazam (CLB), and levetiracetam (LEV) was observed, revealing the effective pharmacotherapies for SCN1A-related seizures. An asymptomatic carrier with a reported pathogenic SCN1A variant was reviewed along with her monozygotic twin sister with DS. Nine novel SCN1A mutations are herein reported, eight of which being classified as pathogenic.
Our study revealed unfavorable outcomes for patients with SCN1A variants. Some patients with SCN1A channelopathy showed specific responsiveness to the pharmacotherapies previously either recommended or contraindicated for these patients. Our study also expands the genotype and provides valuable prognostic insights in patients with SCN1A channelopathy.
SCN1A通道病是癫痫性脑病最广为人知的病因，其表型谱广泛。可变的表达性给临床意义和预后的解读带来困扰。为了研究SCN1A通道病患者的临床表现、药物治疗及预后，我们在台湾进行了这项观察性回顾研究。
对来自多个中心的16例（5例男性和11例女性）已鉴定出SCN1A变异的患者队列进行研究，并记录与表型相关的因素。使用二代测序（NGS）鉴定变异，并通过桑格测序进行确认。使用一组90个癫痫相关基因来鉴定SCN1A变异，并评估一些潜在的SCN1A修饰基因。
癫痫发作的平均起始年龄为10.4个月。在我们的队列中，16例患者中有12例（75%）有不同程度的神经认知后遗症和精神行为合并症。在所有10例德雷维特综合征（DS）患者和2例非DS表型患者中均发现认知障碍。DS患者对药物治疗的反应率也较低。值得注意的是，观察到对丙戊酸（VPA）、氯巴占（CLB）和左乙拉西坦（LEV）有特定的药物治疗倾向，揭示了SCN1A相关癫痫发作的有效药物治疗方法。对一名报告有致病性SCN1A变异的无症状携带者及其患有DS的同卵双胞胎姐妹进行了回顾。本文报告了9个新的SCN1A突变，其中8个被分类为致病性突变。
我们的研究揭示了SCN1A变异患者的不良预后。一些SCN1A通道病患者对先前推荐或禁止用于这些患者的药物治疗表现出特定的反应性。我们的研究还扩展了基因型，并为SCN1A通道病患者提供了有价值的预后见解。
