SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis

<b>Background:</b> <i>SCN1A</i> is one of the most common epilepsy genes. About 80% of <i>SCN1A</i> gene mutations cause Dravet syndrome (DS), which is a severe and catastrophic epileptic encephalopathy. More than 1,800 mutations have been identified in <i>SCN1A</i>. Although it is known that <i>SCN1A</i> is the main cause of DS and genetic epilepsy with febrile seizures plus (GEFS+), there is a dearth of information on the other related diseases caused by mutations of <i>SCN1A</i>. <b>Objective:</b> The aim of this study is to systematically review the literature associated with <i>SCN1A</i> and other non-DS-related disorders. <b>Methods:</b> We searched PubMed and SCOPUS for all the published cases related to gene mutations of <i>SCN1A</i> until October 20, 2021. The results reported by each study were summarized narratively. <b>Results:</b> The PubMed and SCOPUS search yielded 2,889 items. A total of 453 studies published between 2005 and 2020 met the final inclusion criteria. Overall, 303 studies on DS, 93 on GEFS+, three on Doose syndrome, nine on the epilepsy of infancy with migrating focal seizures (EIMFS), six on the West syndrome, two on the Lennox-Gastaut syndrome (LGS), one on the Rett syndrome, seven on the nonsyndromic epileptic encephalopathy (NEE), 19 on hemiplegia migraine, six on autism spectrum disorder (ASD), two on nonepileptic <i>SCN1A</i>-related sudden deaths, and two on the arthrogryposis multiplex congenital were included. <b>Conclusion:</b> Aside from DS, <i>SCN1A</i> also causes other epileptic encephalopathies, such as GEFS+, Doose syndrome, EIMFS, West syndrome, LGS, Rett syndrome, and NEE. In addition to epilepsy, hemiplegic migraine, ASD, sudden death, and arthrogryposis multiplex congenital can also be caused by mutations of <i>SCN1A</i>.