Understanding the precise genetic -basis of disease is one of the critical developments in medicine in the twenty-first century. Genetic testing has revolutionized the diagnosis and treatment of neurological diseases in children. Whole-genome and whole-exome sequencing have particularly been useful in understanding the genetic basis of childhood epileptic encephalopathies characterized by early-onset seizures with significant developmental impairment and regression. In this review we describe the identification of a new epileptic encephalopathy caused by a de novo mutation in the SCN8A gene, which encodes for Na_V1.6, a vital sodium channel in the central nervous system. SCN8A variants in patients with epilepsy result primarily in gain-of-function in Na_v1.6 and hyperexcitability of neurons in the central nervous system. Following the original discovery in 2012 of a de novo mutation in a child with developmental and epileptic encephalopathy (DEE), more than 400 individuals with SCN8A-related disorders have been identified. Clinical manifestations range from movement disorders or intellectual disability only to severe DEE, which includes epileptic encephalopathy with intractable multivariate seizure types, developmental impairment and regression, intellectual disability, and other neurological manifestations. Gain-of-function of the Na_v1.6 channel predicts effectiveness of sodium channel-blocking agents in the treatment of seizures, which has been corroborated by clinical experience. Nevertheless, treatment options remain limited and adverse effects are common. However, with the availability of a growing database of genetic and clinical data along with transfected cell lines and mouse models, more efficacious, targeted, and selective treatments may soon be feasible.

了解疾病的精确遗传基础是 21 世纪医学的重要发展之一。基因检测彻底改变了儿童神经系统疾病的诊断和治疗。全基因组和全外显子组测序在了解儿童癫痫性脑病的遗传基础方面特别有用，这些儿童癫痫性脑病的特征是早发性癫痫发作，伴有显着的发育障碍和退化。在这篇综述中，我们描述了一种由SCN8A基因从头突变引起的新癫痫性脑病的鉴定，该基因编码 Na _V 1.6，这是中枢神经系统中重要的钠通道。SCN8A癫痫患者的变异主要导致 Na _v 1.6 的功能获得和中枢神经系统神经元的过度兴奋。继 2012 年在一名患有发育性和癫痫性脑病 (DEE) 的儿童中最初发现从头突变后，已经确定了 400 多名患有SCN8A相关疾病的个体。临床表现范围从仅运动障碍或智力障碍到严重的 DEE，其中包括具有难治性多变量癫痫发作类型的癫痫性脑病、发育障碍和退化、智力障碍和其他神经系统表现。_{Na v}的函数增益1.6 通道可预测钠通道阻滞剂治疗癫痫发作的有效性，这已得到临床经验的证实。然而，治疗选择仍然有限，不良反应很常见。然而，随着越来越多的遗传和临床数据数据库以及转染细胞系和小鼠模型的可用性，更有效、更有针对性和选择性的治疗可能很快就会变得可行。