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BackgroundUnderstanding disease progression, age-specific comorbidities, medical treatment patterns, and unmet needs can help improve the care pathway of individuals with rare genetic epilepsies. A matched longitudinal cohort study has not been performed for these variables from childhood to adolescence across the whole phenome.MethodsWe identified individuals with likely genetic and non-genetic epilepsy syndromes and onset at ages 0-5 years by linkage across the Cleveland Clinic Health System. We used natural language processing to extract medical terms and procedures from longitudinal electronic health records (EHR) and tested for cross-sectional and temporal associations with genetic epilepsies.FindingsWe identified 503 individuals with genetic epilepsy syndromes and matched controls with epilepsy that did not receive genetic testing. The median age at the first encounter was 0·1 years, 7·9 years at the last encounter, and the mean duration of follow-up was 8·2 years. We extracted 188,295 Unified Medical Language System (UMLS) annotations for statistical analysis across 9,659 encounters. Individuals with genetic epilepsy syndromes received an earlier epilepsy diagnosis and had more frequent and complex encounters with the healthcare system. Notably, the highest enrichment of encounters compared to the non-genetic groups was found during the transition from paediatric to adult care. Our computational approach could validate established comorbidities of genetic epilepsies, such as behavioural abnormality and intellectual disability. We also revealed novel associations for genitourinary abnormalities (OR 1·91, 95% CI: 1·66-2·19, p = 2·39×10-19) linked to a spectrum of underrecognized genetic syndromes.InterpretationThis study identified novel features associated with the likelihood of a genetic epilepsy syndrome and quantified the healthcare utilization of genetic epilepsies compared to matched controls with epilepsy who did not receive genetic testing. Our results strongly recommend early genetic testing to stratify individuals into specialized care paths, thus improving the clinical management of people with genetic epilepsies.FundingNot applicable. |
