A new study identifies numerous genetic mutations that help explain why newborns with congenital heart disease (CHD) have a high risk of neurodevelopmental disorders. Neurodevelopmental disorders (NDDs), which result in cognitive, motor, social, and language impairments, occur in 10% of all children with CHD, and in 50% with severe CHD. Pinpointing genes that play a role in both disorders may help identify those at greatest risk of neurodevelopmental disabilities, allowing for improved monitoring and early intervention. To better understand this overlap, Jason Homsy et al. analyzed de novo (spontaneous) mutations that arose in 1,213 children with CHD, using a method that assesses mutation rates by variant type. Compared with patients who had CHD alone, those with both CHD and neurodevelopmental disorders had a much higher burden of damaging de novo mutations, especially in high heart expression (HHE) genes, which are highly expressed during heart development. Whereas 20% of HHE mutations were collectively associated with CHD, NDD and congenital anomalies, only 2% of these mutations were found to be exclusive to CHD. This genetic overlap suggests that mutations that affect a developing heart can also affect the developing brain, the authors say, and may ultimately allow for earlier identification of CHD patients who are at greatest risk for neurodevelopmental disabilities.