The primary goal of the Epi4K Center Without Walls is to increase understanding of the genetic basis of human epilepsy in order to improve the well-being of patients and family members living with these disorders. This improvement will come in the form of better diagnostics, treatments and cures. To accomplish this goal, Epi4K aims to analyze the exomes and genomes of a large number of well-phenotyped epilepsy patients and families collected by investigators from several major research groups. The specific goals of this project (4 of 7: Epileptic Encephalopathies) are to discover mutations or deletions in genes by mining sequence data from exomes of 500 patients with two severe childhood epileptic encephalopathies. Infantile Spasms (IS) and Lennox Gastaut Syndrome (LGS), to understand how these mutations fit into a broader network of developmental interactions within the brain and to compare the causes of these defined epilepsies with other epileptic encephalopathies (EE) of childhood. Dr. Sherr from UCSF, Dr. Scheffer from the University of Melbourne and Dr. Mefford from the University of Washington will co-direct this project. The discovery of novel genes that lead to IS/LGS and other severe childhood EE in the Epi4K cohorts will further our understanding of epilepsy genetics and lead to a better understanding of epilepsy pathophysiology and to the possibility of better tools for diagnosis and treatment. Epilepsy is one of the most common neurological disorders in humans, affecting up to 3% of the population. Although it is clear that there is a strong genetic component for epilepsy, there are still only a few genes known. The Epi4K project will identify new genes and genetic pathways in epilepsy and will directly benefit individuals with epilepsy and their families through improved diagnostic, prognostic and recurrence risk information. Greater understanding of the genes involved in normal development and function of the brain.