The developmental and epileptic encephalopathies (DEE) are the most severe group of epilepsies affecting 1 in 2000 live births. These disorders, which present in childhood, are catastrophic. One in four children die by 20 years of age and survivors have significant lifelong intellectual, psychiatric, behavioural and motor disabilities. In most children a genetic change causes this severe epilepsy. Although some of these genes have been identified, over 50% of children still cannot be genetically diagnosed. In this Project, we will comprehensively and systematically search the DNA of children with unsolved developmental and epileptic encephalopathies to discover new epilepsy genes. We will also characterise the clinical features of children with abnormalities in these newly discovered genes. This will enable clinicians to interpret genetic results when these children first present with seizures. Our work will lead directly to improved diagnosis, therapy and outcomes for children with these devastating disorders.