This study identifies a previously unrecognized genetic disorder caused by changes in the BHLHE22 gene. Clinical and genetic information from 15 affected individuals in 13 families worldwide revealed a shared pattern of developmental and cognitive delay, movement abnormalities, and defects of the corpus callosum, the structure connecting the two halves of the brain. The disorder occurs in two forms: changes in one copy of BHLHE22 cause a variable condition, whereas changes in both copies, identified in children from consanguineous families, result in a more severe disorder. This finding provides answers for affected families, improves genetic diagnosis and counseling, and advances our understanding of human brain development. (https://jmg.bmj.com/content/early/2026/08/12/jmg-2025-111432)