Abstract
OBJECTIVES: This study investigated the characteristics of adolescent-onset epilepsy (AOE) and conducted genetic tests on a cohort of 76 Korean patients to identify variants and expand the spectrum of mutations associated with AOE. METHODS: Clinical exome sequencing after routine karyotyping and chromosomal microarray was performed to identify causative variants and expand the spectrum of mutations associated with AOE. RESULTS: In cases of AOE without neurodevelopmental delay (NDD), this study identified four likely pathogenic variants (LPVs) or variants of uncertain significance (VUS) and two copy number variations (CNVs). To explore the unique features of AOE; clinical manifestations were compared between patients with and without NDD. The analysis revealed statistically significant differences in the prevalence of males and the yield of genetic testing results. AOE without NDD had a lower prevalence in males (49%) compared to AOE with NDD (60%) (p = 0.007). Genetic alterations: AOE with NDD exhibited a higher frequency of genetic alterations (35%) compared to AOE without NDD (12%) (p = 0.011). Thorough evaluation of AOE can be particularly challenging in adolescent patients. Some individuals may display genetic variations due to a phenomenon known as locus heterogeneity, where different genetic causes lead to similar clinical presentations. CONCLUSIONS: Implementing a robust genetic workflow is crucial for accurately diagnosing AOE, even in cases with complex genetic underpinnings. This study underscores the importance of genetic testing as an essential diagnostic tool for AOE. Identifying genetic variants and understanding their clinical correlations can aid in improving diagnostic accuracy and optimizing treatment approaches for adolescent patients with epilepsy.