While some types of epilepsies present with mild seizures occurring early on in newborns or infants, others present with severe brain disorders called “Epileptic Encephalopathies” (EE). These disorders can cause intellectual disability, drug-resistant epilepsy, and other multi- organ comorbidities.

Childhood epilepsy syndromes characterized by seizure onset in the first year of life with ensuing EE are known as Early Infantile Epileptic Encephalopathies (EIEE). There are many forms of EIEE, each caused by mutations at different genes. EIEEs are associated with developmental delay or regression that might occur before seizure onset. Frequent comorbidities include behavioral and movement disorders, and those that affect many body functions.

Genetic screening in epilepsy patients, widely enabled by the advent of next-generation sequencing (NGS), has allowed for the identification of many different kinds of mutations that cause alterations in the function or expression of specific proteins. The percentage of EE cases believed to result from specific genetic mutations continues to increase as more genetic sequences become available. Understanding how genetic mutations contribute to the pathogenesis of early-onset childhood epilepsy has great importance for diagnosis, treatment, and prevention of epilepsy.