We integrated clinical, electrophysiologic, and molecular data to illustrate the spectrum of epilepsy phenotypes and their mechanistic underpinnings.<h4>Results</h4>Dup15q syndrome demonstrates marked heterogeneity in epilepsy severity and seizure semiology, reflecting variable gene dosing effects, maternal imprinting of UBE3A, and altered GABAergic signaling. This evidence concerns the gene UBE3A and epilepsy.