Genetic developmental and epileptic encephalopathies in adulthood: Gaps in evidence and care

Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of the most severe epilepsies, characterized by seizure onset and neurodevelopmental delay in infancy or childhood, often with additional neurological and systemic comorbidities. Up to 50% of cases have an identifiable genetic cause, with structural etiologies representing a small minority. Although associated with early mortality, many individuals now live into adulthood. Over the past 15 years, advances in genetic diagnosis and understanding of disease mechanisms have created realistic prospects of precision therapies, including gene and RNA therapies. The adult phase of DEEs remains poorly characterized, with limited observational evidence. Adults with DEEs are underrepresented in the literature and often excluded from clinical trials, despite ongoing drug-resistant epilepsy, evolving neurodevelopmental disability, and an increasing burden of comorbidities with age. In this narrative review, we discuss important aspects of care for adults with genetic DEEs, including genetic testing, comorbidities and treatment. We also review available natural history studies, recent clinical trials, and consider how emerging disease-modifying therapies may reshape adult phenotypes and redefine priorities for lifelong care. PLAIN LANGUAGE SUMMARY: Developmental and epileptic encephalopathies (DEEs) are a group of rare diseases that are often caused by genetic changes. They usually begin in childhood with severe epilepsy but can also affect learning, development, and overall health throughout life. This review examines the healthcare needs of adults with DEEs, highlights areas where more research is needed, and explores how new treatments may improve health and quality of life across the lifespan.