In this study, we assembled a cohort of 16 unrelated patients with de novo or inherited heterozygous variants in CHD5. Comparison of the clinical features of these affected subjects showed that genetic alterations of CHD5 are associated with a variable neurodevelopmental disorder frequently characterized by intellectual disability (ID), speech delay, motor delay, behavioral problems, and epilepsy. This evidence concerns the gene CHD5 and neurodevelopmental disorder.