Genetics of Congenital Heart Disease

Abstract Congenital heart disease (CHD) is the most common major congenital anomaly, affecting almost 1% of infants born each year. CHD is highly heritable and is more likely to be found in someone who has a family member with CHD. And, while genetic risk contributes to the majority of CHD, only 40% of people with CHD have a contributing genetic variant identified. Among the most common causes are trisomy 21 and 22q11 deletion. The first single gene causes of CHD were identified through the characterisation of extended families with multiple people affected by CHD. Clinical genetic testing can be performed to identify these known genetic causes of human CHD to provide a genetic diagnosis. Expanding our knowledge regarding the genetic contributions to CHD will ultimately enable better treatment and prevention of CHD. Key Concepts The heart develops from several different cell types, in a process controlled by many genes. Genetic variants lead to human congenital heart disease, including aneuploidies, large genetic deletions or duplications, and single gene variants. Some chromosomal deletions are recurrently observed in people with congenital heart disease and also affect other organ systems. The same genetic variant can lead to different types of congenital heart disease, even within the same family. Understanding the genetic aetiology of congenital heart disease can indicate other important health concerns caused by the same genetic variant.