Genetics of CV diseases

Congenital heart defects (CHD) are the most common congenital defects. As a substantial number of patients with CHD now reach the reproductive age, the cardiologist dealing with grown up patients with CHD is confronted with questions of patients regarding impact of their CHD on pregnancy and offspring, and genetic counselling is becoming more relevant to clinical practice. Developments in the field of clinical genetics do not always facilitate the clinicians' knowledge and reasoning. Interpretation of the often-large DNA datasets is challenging, especially in the light of phenotypic heterogeneity and incomplete penetrance, and requires specific expertise. In this chapter the genetics of CHD are addressed. An overview of 'causative' genes is provided, i.e. genes with a high likelihood to be involved in the development of human CHD and found so far to harbour (likely) pathogenic mutations in patients. In addition, the challenges and limitations in determining such genes are addressed and pitfalls in interpreting DNA variants in these genes discussed. The fact that single genes may in some instances be associated with different forms of CHD, may be explained by the broad range of cellular contribution during embryology, which will be briefly addressed. Finally, practical recommendations in addressing the genetics of CHD are provided.