Molecular Profiling of Polish Pediatric Patients with Epilepsy: A Single-Center Diagnostic Experience Using Next-Generation Sequencing

TL;DR

This study used next-generation sequencing to identify genetic causes of epilepsy in 87 Polish children, finding 88 pathogenic variants in 48 genes, with SCN1A and KCNQ2 being the most common.

Contribution

The study provides a detailed molecular profile of pediatric epilepsy in a Polish cohort using NGS, highlighting genetic heterogeneity and diagnostic utility.

Findings

88 pathogenic or likely pathogenic variants were identified in 48 epilepsy-related genes across 87 patients.

SCN1A and KCNQ2 were the most frequently mutated genes, contributing to 12.6% and 9.2% of cases, respectively.

Developmental and epileptic encephalopathy (DEE) had the highest diagnostic yield at 48%.

Abstract

Introduction: Epilepsy syndromes show marked clinical and genetic heterogeneity, with numerous functionally diverse genes involved in their etiology. Next-generation sequencing (NGS) has facilitated the identification of many monogenic epilepsy syndromes and enables earlier, more accurate diagnosis in pediatric patients. Materials and Methods: This study analyzes the molecular profiles of 87 pediatric patients with various forms of epilepsy in whom pathogenic or likely pathogenic variants were identified. Next-generation sequencing (NGS) using multi-gene epilepsy panels or whole-exome sequencing (WES) was performed. Results: A total of 88 pathogenic or likely pathogenic variants were detected in 48 epilepsy-related genes; 30 variants occurred de novo. SCN1A and KCNQ2 were the most frequent contributors (12.6% and 9.2%, respectively). The highest percentage of positive diagnoses (48%) was observed in patients with developmental and epileptic encephalopathy (DEE), with variants identified in genes including ALG13, ATP1A2, CACNA1A, CDKL5, CHD2, GABRG2, ITPA, KCNQ2, PCDH19, SCN1A, SCN2A, SCN3A, SCN8A, SMC1A, SPTAN1, STXBP1, and UBA5. Pathogenic variants in ANKRD11 were found in four patients with KBG syndrome, while other genes appeared sporadically. Conclusions: Targeted massively parallel sequencing is an effective diagnostic tool for pediatric epilepsy. The presence of numerous single-case findings highlights the high genetic heterogeneity of epilepsy. This approach enabled more precise diagnoses that would not have been achieved through clinical evaluation alone, underscoring the importance of genetic testing for prognosis and treatment planning in pediatric patients with unexplained epilepsy.

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