Steel Dora, Symonds Joseph D, Zuberi Sameer M, Brunklaus Andreas
The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, United Kingdom.
School of Medicine, University of Glasgow, Glasgow, United Kingdom.
Epilepsia. 2017 Nov;58(11):1807-1816. doi: 10.1111/epi.13889. Epub 2017 Sep 7.
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by the onset of prolonged febrile and afebrile seizures in infancy, and evolving to drug-resistant epilepsy with accompanying cognitive, behavioral, and motor impairment. Most cases are now known to be caused by pathogenic variants in the sodium channel gene SCN1A, but several other genes have also been implicated. This review examines current understanding of the role of non-SCN1A genes in DS, and what is known about phenotypic similarities and differences. We discuss whether these are best thought of as minority causes of DS, or as similar but distinct conditions.
Based on a review of literature, a list of genes linked to DS was compiled and PubMed was searched for reports of DS-like phenotypes arising from variants in each. Online Mendelian Inheritance in Man (OMIM) was used to identify further reports relevant to each gene.
Genes that have been reported to cause DS-like phenotypes include SCN2A, SCN8A, SCN9A, SCN1B, PCDH19, GABRA1, GABRG2, STXBP1, HCN1, CHD2, and KCNA2. Many of these genes, however, appear to be associated with their own, different, clinical picture. Other candidate genes for DS have been reported, but there is currently an insufficient body of literature to support their causative role.
Although most cases of DS arise from SCN1A variants, numerous other genes cause encephalopathies that are clinically similar. Increasingly, a tendency is noted to define newly described epileptic disorders primarily in genetic terms, with clinical features being linked to genotypes. As genetic diagnosis becomes more readily available, its potential to guide pathophysiologic understanding and therapeutic strategy cannot be ignored. Clinical assessment remains essential; the challenge now is to develop a gene-based taxonomy that complements traditional syndromic classifications, allowing elements of both to inform new approaches to treatment.
德雷维特综合征（DS）是一种严重的发育性癫痫性脑病，其特征为婴儿期出现长时间的热性和无热惊厥，并逐渐发展为药物难治性癫痫，伴有认知、行为和运动障碍。目前已知大多数病例是由钠通道基因SCN1A中的致病性变异引起的，但其他几个基因也与之相关。本综述探讨了目前对非SCN1A基因在DS中的作用的理解，以及已知的表型异同。我们讨论这些基因最好被视为DS的少数病因，还是类似但不同的病症。
基于文献综述，编制了一份与DS相关的基因列表，并在PubMed上搜索了每个基因变异导致的类似DS表型的报告。使用在线人类孟德尔遗传（OMIM）来识别与每个基因相关的更多报告。
已报道可导致类似DS表型的基因包括SCN2A、SCN8A、SCN9A、SCN1B、PCDH19、GABRA1、GABRG2、STXBP1、HCN1、CHD2和KCNA2。然而，这些基因中的许多似乎都与各自不同的临床症状相关。还报道了其他DS候选基因，但目前文献数量不足，无法支持它们的致病作用。
尽管大多数DS病例源于SCN1A变异，但许多其他基因也会导致临床上相似的脑病。越来越多地注意到一种趋势，即主要从遗传学角度定义新描述的癫痫疾病，临床特征与基因型相关。随着基因诊断越来越容易获得，其指导病理生理理解和治疗策略的潜力不可忽视。临床评估仍然至关重要；现在的挑战是开发一种基于基因的分类法，以补充传统的综合征分类，使两者的要素都能为新的治疗方法提供信息。
