Normal development occurred in only 15% of IS of unknown cause. The majority (85%) had clinically documented developmental delay (15% mild, 20% moderate, and 50% severe) at last assessment (median 2.7 years; interquartile interval 1.71-6.25 years). Predictors of positive developmental outcomes included no delay prior to IS (P < .001), older age of IS onset (median 6 months old), and resolution of IS after initial treatment (P < .001). Additional seizures after IS occurred in 67%, with predictors being seizures prior to IS (P = .018), earlier age of IS onset (median 5 months old), and refractory IS (P = .008). On a research basis, whole exome sequencing identified 15% with de novo variants in known epilepsy genes. Individuals with a genetic finding were more likely to have poor developmental outcomes (P = .035).