Niska efektywność badań genetycznych u dorosłych pacjentów przygotowywanych do operacji z powodu epilepsji

OBJECTIVE: To determine the diagnostic yield of genetic testing in patients undergoing presurgical evaluation for epilepsy. METHODS: We conducted a cohort study including 115 adult patients who underwent presurgical evaluation in the Calgary Epilepsy Program between 2019 and 2023 and who had undergone research exome sequencing. A curated epilepsy gene panel comprising 765 Online Mendelian Inheritance in Man (OMIM)-listed epilepsy-associated genes was applied. Variants were classified according to American College of Medical Genetics and Genomics guidelines and assessed for clinical relevance and association with postsurgical outcomes. RESULTS: Pathogenic or likely pathogenic variants in DEPDC5, NPRL2, KCNT2, and PRRT2 were identified, respectively, in 4 individuals (3.5%, 4/115). All variants met stringent quality criteria with high pathogenicity scores (Combined Annotation Dependent Depletion (CADD) 34-37) and absent or extremely low population frequencies in gnomAD v4.1. None of these patients had intellectual disability, and only one patient (PRRT2) had a positive family history. The patient with the KCNT2 variant underwent epilepsy surgery with good outcome (Engel class ID). SIGNIFICANCE: This presurgical cohort demonstrates a low diagnostic yield of genetic testing in adult epilepsy surgery candidates. However, three of four patients with (likely) pathogenic variants did not have features that would have prompted clinical genetic testing, indicating that their genetic diagnosis would have been missed based on typical clinical genetic testing criteria in many jurisdictions.