Clinical features and genetic analysis of five children with epilepsies due to variants of SCN8A gene
10.3760/cma.j.cn511374-20221020-00702
- VernacularTitle:SCN8A基因变异致癫痫5例患儿的临床特征及遗传学分析
- Author:
Xin ZHANG
1
;
Shiyan QIU
;
Li YANG
;
Yufen LI
;
Na XU
;
Xixi YU
Author Information
1. 锦州医科大学临沂市人民医院研究生培养基地，临沂 276003
- Keywords:
SCN8A gene;
Epilepsy;
Whole exome sequencing;
Genetic variant
- From:
Chinese Journal of Medical Genetics
2024;41(2):174-180
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene. Methods:Clinical data of five children (four males and one female) admitted to Linyi People′s Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected. Whole exome sequencing was carried out for these children, and candidate variants were verified by Sanger sequencing.Results:All of the five children were found to harbor variants of the SCN8A gene. Case 1, who had benign familial infantile epilepsy, inherited a known pathogenic c. 4840A>G variant from his father with similar symptoms. Cases 2 to 4 had presented with intermediate epilepsy. Among these, case 2 has harbored a de novo c. 3967G>A variant which was rated as pathogenic (PS1+ PS2+ PM1+ PM2_Supporting+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics. Cases 3 and 4 were found to respectively harbor a de novo c. 415A>T and a c. 4697C>T variant, which were both rated as likely pathogenic (PS2+ PM1+ PM2_Supporting+ PP3). Case 5, who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome, has harbored a de novo c. 5615G>A variant, which was known to be pathogenic. The children had their age of onset ranging from 2 to 14 months, and all had focal seizures and generalized tonic clonic seizures. Four children (cases 1, 2, 3 and 5) had cluster seizures, four (cases 1 to 4) had become seizure-free after single or dual treatment and showed normal growth and development, whilst case 5 was drug-resistant and showed severe developmental retardation. Conclusion:The five children had new features such as cluster seizures, occasional benign seizures in adulthood, and intermediate epilepsy which are prone to relapse after discontinuation of medication, which may be attributed to the pathogenic variants of the SCN8A gene.
