Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have identified rare, potentially causative de novovariants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novovariants could contribute to this disease. We identified 20 de novovariants in 17 COS probands, which is consistent with the de novomutation rate reported in the adult form of the disease. Interestingly, the missense de novovariants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1and ITGA6have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes.