Single-gene childhood developmental epileptic encephalopathies: a primer for pediatric neuropsychologists

The growing fields of genetics and neurogenetics have brought increased attention to developmental and epileptic encephalopathies (DEEs), a group of rare epilepsy disorders that span genetic and neurological pathology. Among the genetic causes of DEEs, single-gene variants represent a significant and increasingly recognized category. These variants often lead to complex and distinct clinical presentations, including variable seizure types, neurocognitive profiles, and developmental trajectories. Foundational knowledge about these disorders, including their molecular and cellular etiologies, accompanying clinical symptoms, and developmental trajectories, can better inform neuropsychological practice, especially in guiding test selection and recommendations as well as highlighting limitations for evaluation. The primary objective of this paper is to provide an evidence-based primer on single-gene developmental epileptic encephalopathies for pediatric neuropsychologists working with these growing clinical and research populations. The manuscript begins with a broad overview of definitions relevant to the care of those with single-gene epilepsies. The paper then describes the clinical features and neurocognitive outcomes associated with the eight most common single-gene pediatric-onset epilepsies, which is subsequently followed by a brief overview of 13 additional single-gene pediatric-onset epilepsies. The paper concludes with a summary of the treatment landscape and discusses current considerations for neuropsychological assessment with this population.