Congenital Heart Disease Gene Mutations May Contribute to Neurodevelopmental Delays

Results from an exome sequencing study demonstrated a link between genetic mutations related to congenital heart disease and neurodevelopmental disorders in children.

Exome sequencing has revealed a previously unknown relationship between genetic mutations linked to congenital heart disease and neurodevelopmental disorders in children.

The study results could have major implications for the screening and treatment of children born with structural heart defects — the most common type of birth defect in the US.

While surgical treatments are often performed early on to address congenital heart defects, previous research has shown that many of these children exhibit signs of neurodevelopmental and neurobehavioral problems once they reach school age.

In the current study, published in Science, researchers from the Bench to Bassinet Program’s Pediatric Cardiac Genomics Consortium sought to identify any potential genetic links between congenital heart disease and neurodevelopmental abnormalities.

The researchers performed exome sequencing on 1220 family trios that included a child with congenital heart disease and the mother and father. Approximately 2% of children with moderate to severe congenital heart disease were found to have a substantial number of protein-damaging de novo mutations, compared to 20% of children with congenital heart disease and another structural birth defect and/or a neurodevelopmental abnormality. Many of the genes involved were found to be highly expressed in the developing heart and brain, “suggesting that a single mutation can contribute to both congenital heart disease and neurodevelopmental abnormalities,” investigator Christine Seidman, MD, of Brigham and Women’s Hospital, said in a statement.

The mutations primarily affected genes involved in morphogenesis, chromatin modification, and transcriptional regulation. Several mutations were found in RBFOX2, which regulates mRNA splicing.

While the findings need to be replicated before a clinical test can be developed, the results are especially promising for the development of genetic testing that could contribute to the detection and early intervention of developmental delays in children with congenital heart disease. Doing so could ultimately limit developmental delays and improve patient outcomes.


  1. Homsy J, Zaidi S, Shen Y, et al. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science. 2015; doi:10.1126/science.aac9396.
  2. Link between congenital heart disease and neurodevelopment issues in children found [news release]. National Institutes of Health; Bethesda, MD: December 4, 2015. Accessed December 4, 2015.

This article originally appeared on Neurology Advisor