To explore the genetic characteristics of children with epilepsy encephalopathy (EE), and to determine the molecular level etiology. Methods: A total of 86 children with unexplained EE were recruited. Whole exon sequencing (WES) and genomic copy number variant (CNV) analysis were performed. Re? sults: Among the 86 children with EE, there were 51 cases (59.30%) of genetic variation with definite pathogenicity, including 46 (53.49%) with gene mutation and 5 (5.81%) with CNV mutation; among these 51 cases, 44 (86.27%) had de novo variants. Of the 86 children with EE, 11 experienced disease onset during the neonatal period, 52 during infancy, 18 during early childhood, and 5 during preschool age. Conclusion: The gene mutation rate in childhood EE is high. Mutation is mainly de novo, and onset occurs primarily during infancy and early childhood.