This review examines the intersection of genomics, epilepsy, and neurodevelopment in complex neurodevelopmental disorders, emphasizing Dup15q syndrome as a model for understanding phenotypic variability.<h4>Methods</h4>Authors conducted a clinical (non-systematic) review of the literature based on their experience with three patients with Dup15q who responded dramatically to neurostimulation. This evidence concerns the gene GREM1 and neurodevelopmental disorder.