We and others have reported de novo loss-of-function variants [24–28] and microdeletions [29,30] encompassing HNRNPU in pediatric patients with a severe, and often treatment refractory, developmental and epileptic encephalopathy (DEE) characterized by early-onset epilepsy, moderate to severe developmental delay, autistic features, structural brain abnormalities, hypotonia, short stature and variable renal and cardiac abnormalities. The gene discussed is HNRNPU; the disease is developmental and epileptic encephalopathy.