Epilepsy is now recognized as the second most common neurological disease in China. To determine the genetic cause of epileptic encephalopathy, we performed a multiomics study using mouse models of controls, anticonvulsant mice treated with five drugs and epileptic mice. Based on genome-wide profiling analysis, we discovered four genes in the epileptic mouse group with differentially-expressed mRNA. After isobaric tags for relative and absolute quantification (iTRAQ) validation, only one gene, SNCA, remained, which was associated with apoptotic response of neuronal cells, and regulation of dopamine release and transport. We also identified three miRNAs targeting SNCA, out of which mmu-miR-21a-3p demonstrated a seven-fold change in expression between control and epileptic mice.