Clinical and genetic analysis of 23 Chinese children with epilepsy associated with KCNQ2 gene mutations

Abstract Objective To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2 ‐related epilepsy. Methods A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next‐generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations. Results We identified 23 KCNQ2 gene mutations. 73.9% ( n = 17) of the mutation sites were located in S5–S6 segments and the C‐terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video‐electro‐encephalography, three cases with self‐limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2 ‐DEE. At the final follow‐up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2 ‐DEE had mild to severe developmental backwardness. Significance Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2 ‐related epilepsy. The gene mutation sites are mostly located in S5–S6 segments and the C‐terminal region, and the former is usually associated with KCNQ2 ‐DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2 ‐DEE. Some cases with KCNQ2 ‐related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2 ‐DEE. Plain Language Summary This article reports 23 cases of children with KCNQ2 ‐related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2 ‐related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2 ‐related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.