AUTHOR=Zeng Qi , Yang Ying , Duan Jing , Niu Xueyang , Chen Yi , Wang Dan , Zhang Jing , Chen Jiaoyang , Yang Xiaoling , Li Jinliang , Yang Zhixian , Jiang Yuwu , Liao Jianxiang , Zhang Yuehua 

TITLE=SCN2A-Related Epilepsy: The Phenotypic Spectrum, Treatment and Prognosis

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=15

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.809951

DOI=10.3389/fnmol.2022.809951

ISSN=1662-5099

ABSTRACT=<sec><title>Objective</title><p>The aim of this study was to analyze the phenotypic spectrum, treatment, and prognosis of 72 Chinese children with <italic>SCN2A</italic> variants.</p></sec><sec><title>Methods</title><p>The <italic>SCN2A</italic> variants were detected by next-generation sequencing. All patients were followed up at a pediatric neurology clinic in our hospital or by telephone.</p></sec><sec><title>Results</title><p>In 72 patients with <italic>SCN2A</italic> variants, the seizure onset age ranged from the first day of life to 2 years and 6 months. The epilepsy phenotypes included febrile seizures (plus) (<italic>n</italic> = 2), benign (familial) infantile epilepsy (<italic>n</italic> = 9), benign familial neonatal-infantile epilepsy (<italic>n</italic> = 3), benign neonatal epilepsy (<italic>n</italic> = 1), West syndrome (<italic>n</italic> = 16), Ohtahara syndrome (<italic>n</italic> = 15), epilepsy of infancy with migrating focal seizures (<italic>n</italic> = 2), Dravet syndrome (<italic>n</italic> = 1), early infantile epileptic encephalopathy (<italic>n</italic> = 15), and unclassifiable developmental and epileptic encephalopathy (<italic>n</italic> = 8). Approximately 79.2% (57/72) patients had varying degrees of developmental delay. All patients had abnormal MRI findings with developmental delay. 91.7% (55/60) patients with <italic>de novo SCN2A</italic> variants had development delay, while only 16.7% (2/12) patients with inherited <italic>SCN2A</italic> variants had abnormal development. 83.9% (26/31) <italic>SCN2A</italic> variants that were located in transmembrane regions of the protein were detected in patients with development delay. Approximately 69.2% (9/13) <italic>SCN2A</italic> variants detected in patients with normal development were located in the non-transmembrane regions. Approximately 54.2% (39/72) patients were seizure-free at a median age of 8 months. Oxcarbazepine has been used by 38 patients, and seizure-free was observed in 11 of them (11/38, 28.9%), while 6 patients had seizure worsening by oxcarbazepine. All 3 patients used oxcarbazepine and with seizure onset age &gt; 1 year presented seizure exacerbation after taking oxcarbazepine. Valproate has been used by 53 patients, seizure-free was observed in 22.6% (12/53) of them.</p></sec><sec><title>Conclusion</title><p>The phenotypic spectrum of <italic>SCN2A</italic>-related epilepsy was broad, ranging from benign epilepsy in neonate and infancy to severe epileptic encephalopathy. Oxcarbazepine and valproate were the most effective drugs in epilepsy patients with <italic>SCN2A</italic> variants. Sodium channel blockers often worsen seizures in patients with seizure onset beyond 1 year of age. Abnormal brain MRI findings and <italic>de novo</italic> variations were often related to poor prognosis. Most <italic>SCN2A</italic> variants located in transmembrane regions were related to patients with developmental delay.</p></sec>