Recent advances in genetic testing technologies have revolutionised the identification of genetic abnormalities in early onset developmental and epileptic encephalopathies (DEEs). In this Review, we provide an update on the expanding landscape of genetic factors contributing to DEEs, encompassing over 800 reported genes. We focus on the cellular and molecular mechanisms driving epileptogenesis, with an emphasis on emerging therapeutic strategies and effective treatment options. We explore noteworthy, novel genes linked to DEE phenotypes, such as gBRAT-1 and GNAO1, and gene families such as GRIN and HCN. Understanding the network-level effects of gene variants will pave the way for potential gene therapy applications. Given the diverse comorbidities associated with DEEs, a multidisciplinary team approach is essential. Despite ongoing efforts and improved genetic testing, DEEs lack a cure, and treatment complexities persist. This Review underscores the necessity for larger international prospective studies focusing on both seizure outcomes and developmental trajectories.
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