As we continue with our focus on genetics and genomics research, PCHA welcomes NIH medical officer Dr. Jonathan Kaltman. Dr. Kaltman provides an overview of a recent study that uses genomic data to establish a genetic link between congenital heart disease (CHD) and neurodevelopmental disorders. This study provides an important example of how genetics and genomics research can help us understand the genetic causes of CHD and other congenital anomalies.
The journal Science recently published a study performed by the Pediatric Cardiac Genomics Consortium evaluating the genetic cause of congenital heart disease (CHD). The investigators also tried to determine if genetics can explain why many children with CHD also have other medical conditions, including neurodevelopmental disorders and other congenital problems. You can find the complete study here.
About this Study:
- The purpose of this study was to determine the genetic cause of severe CHD and its related medical problems.
- Genetic sequencing was performed on 1,213 children with CHD and their parents and compared to families who did not have CHD.
- Participants with CHD were also evaluated for neurodevelopmental disorders, such as learning disabilities or attention deficit/hyperactivity disorder, and other congenital problems, such as cleft lip.
- Children with severe CHD have a high number of spontaneous mutations.
- The finding of a spontaneous mutation was especially strong in patients with CHD and another structural birth defect and/or neurodevelopmental disorders suggesting that these medical conditions happening together is likely due to a genetic cause.
- Spontaneous mutations occurred in 20% of subjects with CHD, neurodevelopmental disorders, and another birth defect. They occurred in 5-10% of subjects with CHD and either a neurodevelopmental disorder or another birth defect. They occurred in only 2% of subjects with only CHD.
- Many of the genes with mutations work in early development in both the heart and the brain, suggesting that a single mutation may cause both CHD and neurodevelopmental disorders.
- Defects in certain genes result in a very high risk for developing neurodevelopment disorders associated with the CHD.
What this Means:
- Neurodevelopmental disorders in children with CHD have often been thought to be caused by abnormal circulation and/or stresses associated with surgery and post-operative care. The findings from this study suggest that underlying genetics may also play an important role.
- If these findings are repeated in other experiments, clinical genetic tests might be developed that can identify patients at high risk for developing neurodevelopmental abnormalities, enabling clinicians to target these patients for early therapy with the ultimate goal of improving their outcome.
These findings are helping to identify new molecular pathways that are important to heart and brain development improving basic knowledge of how the human body develops and providing understanding of the causes of various birth defects.
Jonathan R. Kaltman, M.D., is Chief of the Heart Development and Structural Diseases Branch in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). Dr. Kaltman provides leadership for the Pediatric Cardiac Genomics Consortium and also helps oversee the Pediatric Heart Network. Prior to joining the NHLBI, Dr. Kaltman served as an assistant professor at the Children’s Hospital of Philadelphia at the University of Pennsylvania School of Medicine. He then joined the Children’s National Medical Center in D.C. as an assistant clinical professor where he continues to hold a part-time position. Dr. Kaltman received his B.S. in Molecular Biophysics and Biochemistry from Yale University and his M.D. from Emory University School of Medicine.