AUTHOR=Fang Hongjun , Hu Wenjing , Kang Qingyun , Kuang Xiaojun , Wang Lijuan , Zhang Xiao , Liao Hongmei , Yang Liming , Yang Haiyan , Jiang Zhi , Wu Liwen 

TITLE=Clinical characteristics and genetic analysis of pediatric patients with sodium channel gene mutation-related childhood epilepsy: a review of 94 patients

JOURNAL=Frontiers in Neurology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1310419

DOI=10.3389/fneur.2023.1310419

ISSN=1664-2295

ABSTRACT=<sec><title>Objective</title><p>This study aimed to examine the clinical and gene-mutation characteristics of pediatric patients with sodium channel gene mutation-related childhood epilepsy and to provide a basis for precision treatment and genetic counseling.</p></sec><sec><title>Methods</title><p>The clinical data from 94 patients with sodium channel gene mutation-related childhood epilepsy who were treated at Hunan Children's Hospital from August 2012 to December 2022 were retrospectively evaluated, and the clinical characteristics, gene variants, treatment, and follow-up status were analyzed and summarized.</p></sec><sec><title>Results</title><p>Our 94 pediatric patients with sodium channel gene variant-related childhood epilepsy comprised 37 girls and 57 boys. The age of disease onset ranged from 1 day to 3 years. We observed seven different sodium channel gene variants, and 55, 14, 9, 6, 6, 2, and 2 patients had <italic>SCNlA, SCN2A, SCN8A, SCN9A, SCN1B, SCN11A</italic>, and <italic>SCN3A</italic> variants, respectively. We noted that 52 were reported variants and 42 were novel variants. Among all gene types, <italic>SCN1A, SCN2A</italic>, and <italic>SCN8A</italic> variants were associated with an earlier disease onset age. With the exception of the <italic>SCN1B</italic>, the other six genes were associated with clustering seizures. Except for variants <italic>SCN3A</italic> and <italic>SCN11A</italic>, some patients with other variants had status epilepticus (SE). The main diagnosis of children with <italic>SCN1A</italic> variants was Dravet syndrome (DS) (72.7%), whereas patients with <italic>SCN2A</italic> and <italic>SCN8A</italic> variants were mainly diagnosed with various types of epileptic encephalopathy, accounting for 85.7% (12 of 14) and 88.9% (8 of 9) respectively. A total of five cases of sudden unexpected death in epilepsy (SUDEP) occurred in patients with <italic>SCN1A, SCN2A</italic>, and <italic>SCN8A</italic> variants. The proportion of benign epilepsy in patients with <italic>SCN9A, SCN11A</italic>, and <italic>SCN1B</italic> variants was relatively high, and the epilepsy control rate was higher than the rate of other variant types.</p></sec><sec><title>Conclusion</title><p>Sodium channel gene variants involve different epileptic syndromes, and the treatment responses also vary. We herein reported 42 novel variants, and we are also the first ever to report two patients with <italic>SCN11A</italic> variants, thereby increasing the gene spectrum and phenotypic profile of sodium channel dysfunction. We provide a basis for precision treatment and prognostic assessment.</p></sec>