Environmental and treatment‐related factors associated with developmental outcomes in genetic epilepsies

Résumé fourni par la source

OBJECTIVE: The mechanistic effects of genetic variants underlying genetic neurodevelopmental disorders (NDDs) are widely studied, but the contribution of external factors remains largely unexplored. METHODS: In this cross-sectional study using the Simons Searchlight population dataset, we examined caregiver-reported environmental exposures and functional outcomes from 970 individuals with (67%) and without (33%) epilepsy across 93 NDDs. The primary outcome was adaptive function (Vineland-3) at last follow-up, with quality of life (Quality of Life Inventory-Disability) and autism symptoms (Social Communication Questionnaire-Lifetime) as secondary analyses. RESULTS: = 19.6%, p = .003). Importantly, the additional variance explained by environmental exposures was different across genes, ranging from ~15% (SCN2A, SLC6A1) to >30% (16p11.2 deletion), suggesting gene-specific vulnerability. Overall, ~60% of variance in developmental outcomes remained unexplained, motivating further studies on genome and exposome influences. SIGNIFICANCE: Our findings highlight genetic NDDs as genome-informed yet exposure-sensitive disorders. We found several external factors that both represent markers of epilepsy severity and may support early, genetically informed seizure management and careful stewardship of treatment exposures. Prospective, controlled studies are needed to disentangle the developmental effects of the underlying disease from treatment-related factors.

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