The utility of CNV analysis in identifying the molecular etiology of pediatric epilepsy patients

Copy number variations (CNVs) are considered to be associated with various neurocognitive disorders, particularly severe pediatric conditions such as intellectual disability and epilepsy. In this study, our aim is to determine the distribution and pathogenicity of CNVs in pediatric epilepsy patients, thereby expanding the spectrum of related syndromes or gene phenotypes, explore potential new epilepsy genes within CNVs.

We collected clinical data from 425 pediatric epilepsy patients and performed WES, including both pathogenic variant analysis and CNV analysis. Variants were classified per ACMG guidelines. Analyzed the phenotypic characteristics associated with genetic diagnostic results and performed further research and analysis on diagnostic CNVs.

Among the 425 pediatric epilepsy patients, diagnostic SNVs/indels were detected in 104 cases (24.5%). CNV testing revealed 49 cases with diagnostic CNVs (11.5%). For patients with epilepsy phenotypes unexplained by CNVs, two potential epilepsy genes were suggested through analysis.

CNV analysis significantly improves the genetic diagnostic yield in pediatric epilepsy patients, achieving a rate of 11.5%. Patients with developmental delay or cardiopathy are more likely to harbor diagnostic CNVs. In-depth analysis of diagnostic CNVs can identify the genetic etiology in epilepsy patients, guide follow-up strategies, and facilitate the discovery of promising candidate epilepsy genes.

CNV analysis can enhance the molecular diagnostic capability of epilepsy. Patients with developmental delay or cardiac disease are more likely to have diagnostic CNVs. In-depth analysis of CNVs can help uncover potential candidate epilepsy genes.