Genetic Testing in Adult Patients With Epilepsy: Genetic Risk Index for Seizure Etiology for Identifying Optimal Candidates.

Clinical patient-selection score for genetic testing (Gen-RISE) derived by multivariable logistic regression

This single-center cross-sectional study (Stanford, 508 adult patients evaluated between 2018 and 2024) assessed the diagnostic yield of genetic testing in adult epilepsy and developed a clinical patient-selection score, Gen-RISE. Pathogenic variants were identified in 32.9% of patients, with exome sequencing providing the highest yield (41.7%), ahead of gene panels (30.3%) and microarray (21.8%). Intellectual disability/developmental delay (OR 3.41), seizure onset before age 3 (OR 1.96) and abnormal EEG (OR 1.29) were associated with genetic epilepsy. A Gen-RISE above 0 predicted a >50% likelihood of identifying a pathogenic variant, with 98.6% sensitivity in an independent literature-based validation cohort. The authors highlight a marked testing delay (11.2 years on average) reflecting underuse.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A pragmatic, publicly available tool addressing a real need: streamlining access to genetic testing in adult epilepsy, a population where the indication remains poorly codified. The clear superiority of exome over panels and microarray supports WES as a first-tier test. External validation is literature-based, and the score needs prospective multicenter confirmation before wide deployment.

Analysis by Dr Thibaut Benquey