Congenital heart disease: current knowledge about causes and inheritance

Med J Aust. 2012 Aug 6;197(3):155-9. doi: 10.5694/mja12.10811.


About 80% of congenital heart disease (CHD) is multifactorial and arises through various combinations of genetic and environmental contributors. About 20% of cases can be attributed to chromosomal anomalies, Mendelian syndromes, non-syndromal single gene disorders or teratogens. Down syndrome and velocardiofacial syndrome are the most commonly seen syndromes in patients with CHD. To date, more than 30 genes have been linked to non-syndromal forms of CHD. Their contribution to CHD remains unknown but is presumed to be relatively small. There is limited evidence for the contribution of specific environmental factors to CHD causation. However, folic acid supplementation in the pre- and peri-conception period, ensuring rubella vaccination has been completed before pregnancy, and maintaining good glycaemic control in mothers with diabetes may reduce the risk of CHD in infants. Recurrence risks vary between different types of non-syndromal CHD with multifactorial inheritance, and can be as high as 10% when two or more siblings are affected. Generally, the recurrence risk increases if a parent rather than a sibling is affected, particularly when the affected parent is the mother. Individualised recurrence risks can be generated for members of families affected by CHD after obtaining a detailed family history, including accurate cardiac diagnoses for all affected members. High-throughput genetic techniques can accelerate gene discovery and improve our ability to provide individualised genetic counselling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromosome Aberrations
  • Environment
  • Genetic Diseases, Inborn / genetics
  • Heart Defects, Congenital / etiology*
  • Heart Defects, Congenital / genetics
  • Humans
  • Risk Factors
  • Teratogens


  • Teratogens