钠通道8α(SCN8A)突变包括一系列具有不同临床表现的癫痫表型,提出诊断挑战。我们介绍了一例9岁男性,患有SCN8A基因相关的发育性和癫痫性脑病(DEE),以婴儿期以来的全身性强直阵挛性癫痫发作(GTCS)为特征。尽管用多种抗癫痫药物(AED)治疗,包括苯妥英,丙戊酸盐,左乙拉西坦,卡马西平,还有Cobazam,癫痫发作控制仍然难以捉摸,促使基因检测。全外显子组测序证实了杂合突变(p。Phe210Ser)在SCN8A外显子6中,指示DEE-13。功能研究揭示了SCN8A变体的功能获得机制,导致离子通道活性增强和激活的电压依赖性改变。尽管治疗调整,患者的癫痫发作持续到托吡酯被引入,提供部分救济。SCN8A,编码Nav1.6钠通道,调节神经元兴奋性,突变导致持续电流增加和过度兴奋。早期癫痫发作和发育迟缓是SCN8A相关DEE的标志。这个案例突出了基因检测在难治性癫痫治疗中的重要性,指导个性化治疗策略。钠通道阻滞剂如苯妥英和卡马西平通常是一线治疗,而托吡酯是SCN8A相关DEE的潜在辅助选择。总的来说,该病例强调了SCN8A相关癫痫性脑病的诊断和治疗复杂性,强调长期监测和个性化治疗方法对优化难治性癫痫结局的重要性.
Sodium channel 8 alpha (SCN8A) mutations encompass a spectrum of epilepsy phenotypes with diverse clinical manifestations, posing diagnostic challenges. We present a
case of a nine-year-old male with SCN8A gene-associated developmental and epileptic encephalopathies (DEEs), characterized by generalized tonic-clonic seizures (GTCS) since infancy. Despite treatment with multiple antiepileptic drugs (AEDs), including phenytoin, valproate, levetiracetam, carbamazepine, and clobazam, seizure control remained elusive, prompting genetic testing. Whole exome sequencing confirmed a heterozygous mutation (p.Phe210Ser) in SCN8A exon 6, indicative of DEE-13. Functional studies revealed a gain-of-function mechanism in SCN8A variants, resulting in heightened ion channel activity and altered voltage dependence of activation. Despite treatment adjustments, the patient\'s seizures persisted until topiramate was introduced, offering partial relief. SCN8A, encoding Nav1.6 sodium channels, modulates neuronal excitability, with mutations leading to increased persistent currents and hyperexcitability. Early seizure onset and developmental delays are hallmarks of SCN8A-related DEE. This
case highlights the significance of genetic testing in refractory epilepsy management, guiding personalized treatment strategies. Sodium channel blockers like phenytoin and carbamazepine are often first-line therapies, while topiramate presents as a potential adjunctive option in SCN8A-related DEE. Overall, this
case underscores the diagnostic and therapeutic complexities of managing SCN8A-related epileptic encephalopathy, emphasizing the importance of long-term monitoring and personalized treatment approaches for optimizing outcomes in refractory epilepsy.