Cytogenetics (CL Martin, Section Editor)

Current Genetic Medicine Reports

, Volume 2, Issue 3, pp 168-178

Copy Number Variation in Congenital Heart Defects

  • Julie LanderAffiliated withDepartment of Pediatrics, University of Cincinnati College of Medicine and Cincinnati Children’s Hospital
  • , Stephanie M. WareAffiliated withDepartment of Pediatrics, Indiana University School of MedicineDepartment of Medical and Molecular Genetics, Indiana University School of Medicine Email author 


Congenital heart defects (CHDs) are the most common birth defect and a major contributor to mortality, morbidity, and healthcare costs throughout the world. Although improvements in surgical advances and cardiac care have increased the lifespan of individuals with CHDs, the underlying etiologies of disease remain elusive and there have been no interventions that decrease disease incidence. Genetic, epigenetic, and environmental factors all influence the development of CHDs, and an improved understanding of causation is a prerequisite for prevention. Genetic causes of CHDs include both structural chromosome abnormalities and single gene disorders. Copy number variation (CNV), or submicroscopic chromosomal deletions or duplications, has emerged as an important contributor to congenital genetic disorders, including CHDs, and has identified critical dosage sensitive genes important for cardiac development. Common CNVs associated with highly penetrant CHDs were first identified in genomic disorders such as 22q11.2 deletion syndrome and Williams–Beuren syndrome. More recently, research investigations and clinical diagnostic testing support a role for CNVs in CHDs with extracardiac abnormalities (ECAs) as well as isolated CHD. It is estimated that CNVs contribute to 3–25 % of CHDs with ECAs and 3–10 % of isolated CHDs. While somewhat less clear, new evidence suggests that there is an increase in rare, large, genic CNVs in patients with CHDs, indicating that the overall CNV burden may also be an important factor in disease. As genetic testing for CHDs moves forward, CNVs will play an important role in diagnosis and gene discovery.


Cardiovascular malformation Dosage sensitive gene Chromosome microarray Genetic testing