DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES: FROM GENETIC HETEROGENEITY TO PHENOTYPIC CONTINUUM

Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plasticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.

Automated summary

Developmental and epileptic encephalopathies (DEEs) are a group of disorders characterized by early-onset severe epileptic seizures, EEG abnormalities, and developmental impairment. DEEs can be caused by genetic and nongenetic factors, with mutations in various genes playing a role. Research in animal models and clinical trials have helped uncover the pathophysiological mechanisms underlying DEEs and explore different treatment options.