Germline Genetic Variants and Epilepsy Surgery Response: Individual Participant Pooled Analysis of 272 Patients.

In 30 seconds

This systematic review and individual-participant pooled analysis examined seizure outcomes after resection or laser ablation in 272 people with pathogenic or likely pathogenic germline epilepsy variants, excluding tuberous sclerosis. At a median follow-up of 24 months (interquartile range 12-48.0), seizure freedom varied by genetic category (overall p < 0.001): it was most frequent in vascular disorders, 14/19 (73.6%), and GATORopathies, 79/120 (65.8%), and less frequent in channelopathies, 13/43 (30.0%), and synaptopathies, 4/18 (22.2%).

Key findings

• Seizure freedom differed across etiologic categories (overall p < 0.001), ranging from 14/19 (73.6%) in vascular disorders to 4/18 (22.2%) in synaptopathies.
• GATORopathies had seizure freedom in 79/120 (65.8%); channelopathies in 13/43 (30.0%).
• Among cases with imaging results, 208/253 (82.2%) had epileptogenic MRI lesions, including 64% of channelopathies and 80% of synaptopathies.
• In univariate comparisons, odds of seizure freedom were lower for synaptopathies (OR 0.23, 95% CI 0.05-0.77) and channelopathies (OR 0.22, 95% CI 0.09-0.48) than for other categories.

Why it matters

The findings suggest that genetic diagnosis alone does not determine surgical outcome: seizure freedom differed substantially by biological pathway, and MRI-visible lesions were common even in categories with lower reported success. This supports considering both genotype and the nature of the epileptogenic substrate when interpreting surgical outcomes, while highlighting the need for better standardized evidence.

What to keep in mind

The pooled evidence combines published cases and institutional cohorts, and follow-up varied (median 24 months; interquartile range 12-48.0). The reported category comparisons are univariate.