AUTHOR=Ding Jiangwei , Wang Lei , Jin Zhe , Qiang Yuanyuan , Li Wenchao , Wang Yangyang , Zhu Changliang , Jiang Shucai , Xiao Lifei , Hao Xiaoyan , Hu Xulei , Li Xinxiao , Wang Feng , Sun Tao 

TITLE=Do All Roads Lead to Rome? Genes Causing Dravet Syndrome and Dravet Syndrome-Like Phenotypes

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.832380

DOI=10.3389/fneur.2022.832380

ISSN=1664-2295

ABSTRACT=<sec><title>Background</title><p>Dravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene <italic>SCN1A</italic>, which encodes the voltage-gated sodium channel Na<sub>V</sub>1. 1 in the brain. While <italic>SCN1A</italic> mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to <italic>SCN1A</italic>. Particularly for healthcare providers, a deep understanding of these pathogenic genes is useful in properly selecting and adjusting drugs in a more effective and timely manner.</p></sec><sec><title>Objective</title><p>The purpose of this study was to identify genes other than <italic>SCN1A</italic> that may also cause DS or DS-like phenotypes.</p></sec><sec><title>Methods</title><p>A comprehensive search of relevant Dravet syndrome and severe myoclonic epilepsy in infancy was performed in PubMed, until December 1, 2021. Two independent authors performed the screening for potentially eligible studies. Disagreements were decided by a third, more professional researcher or by all three. The results reported by each study were narratively summarized.</p></sec><sec><title>Results</title><p>A PubMed search yielded 5,064 items, and other sources search 12 records. A total of 29 studies published between 2009 and 2021 met the inclusion criteria. Regarding the included articles, seven studies on <italic>PCDH19</italic>, three on <italic>SCN2A</italic>, two on <italic>SCN8A</italic>, five on <italic>SCN1B</italic>, two on <italic>GABRA1</italic>, three on <italic>GABRB3</italic>, three on <italic>GABRG2</italic>, and three on <italic>STXBP1</italic> were included. Only one study was recorded for <italic>CHD2, CPLX1, HCN1</italic> and <italic>KCNA2</italic>, respectively. It is worth noting that a few articles reported on more than one epilepsy gene.</p></sec><sec><title>Conclusion</title><p>DS is not only identified in variants of <italic>SCN1A</italic>, but other genes such as <italic>PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1</italic> can also be involved in DS or DS-like phenotypes. As genetic testing becomes more widely available, more genes associated with DS and DS-like phenotypes may be identified and gene-based diagnosis of subtypes of phenotypes in this spectrum may improve the management of these diseases in the future.</p></sec>