Abstract
Developmental and epileptic encephalopathies (DEEs) are among the most severe and difficult to treat epilepsies. Two broad strategies for understanding the etiology and impacts of DEEs include genetic and complex adaptive systems approaches. This review, inspired by the 2024 Merritt-Putnam Symposium, describes current perspectives of DEE, identifies limitations of current views, and discusses potential novel ways forward. First, we discuss the rationale for a reevaluation of the role of seizures in the pathogenesis of cognitive and behavioral impairments in DEE. Second, we discuss newly emerging methods employing neural organoids to study brain development and DEE in vitro. Third, we present recent precision therapy approaches for the clinical treatment of DEE. Lastly, we discuss computational systems approaches to understanding the genetic landscape of DEE. The severe and multifaceted impacts of DEE and associated comorbidities underscore the necessity of novel interdisciplinary approaches to produce an improved understanding of etiology and more effective treatment strategies.