Next-generation sequencing in children with epilepsy: The importance of precise genotype–phenotype correlation

Abstract

AimThe primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype–phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients. MethodsThis single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0–19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype–phenotype correlation was performed. ResultsOut of 175 patients, described pathogenic variants or novel variants with clear pathogenic impact were identified in 30 patients (17.14%). Genotype–phenotype correlations and parental DNA analysis were performed, and genetic diagnosis was confirmed on the basis of the results in another 16 out of 175 patients (9.14%). The diagnostic yield of our study increased from 30 to 46 patients (by 53.33%) by the precise genotype–phenotype correlation. InterpretationWe emphasize a complex genotype–phenotype correlation and a multidisciplinary approach in evaluating the results of the NGS epilepsy gene panel, which enables the most accurate genetic diagnosis and correct interpretation of results.