Abstract:

Objective To investigate the clinical and genetic characteristics of children with epilepsy caused by variations of the KCNQ2 gene (OMIM #602235). Methods The clinical data of 24 children with KCNQ2 gene variants (NM_172107) detected by whole-exome sequencing (WES) from October 2018 to November 2022 were analyzed, and the genotypic characteristics and treatment were analyzed. Results A total of 24 children (14 boys and 10 girls) with epilepsy caused by KCNQ2 gene variations were included. The age of the first seizure in these children ranged from 17 hours after birth to 5 years old. Among them, 16 children (66.7%) were younger than 6 months. According to the clinical prognosis, there were 1 case of benign familial neonatal epilepsy (BFNE), 6 cases of benign familial infantile epilepsy (BFIE), 4 cases of self-limited epilepsy syndrome that could not be classified, and 13 cases of KCNQ2-related developmental and epileptic encephalopathy (KCNQ2-DEE). The main genetic variation was missense mutation (62.5%), and 7 new KCNQ2 mutation sites were found. Among them, c.1411C>T was evaluated as pathogenic, c.602G>C, c.1031G>A, c.2159_2173del (p.720_725delinsR) was evaluated as likely pathogenic. The median follow-up time of the 24 patients was 40 months. 13 patients had varying degrees of developmental delay in KCNQ2-DEE, and the remaining 11 patients had good overall prognosis and normal cognitive development. Conclusions The age of seizures associated with KCNQ2 variation is mainly distributed in the neonatal period and early infancy. The prognosis of KCNQ2-DEE is poor. It is recommended that genetic testing should be performed as early as possible for the diagnosis of unexplained seizures in infancy.

Key words: KCNQ2 gene, benign familial neonatal epilepsy, benign familial infantile epilepsy, early-onset epileptic encephalopathy, potassium channel