The genetics of congenital heart disease: new genes, mechanisms and attitudes

Abstract

Congenital Heart Disease (CHD) affects 6–8 per 1000 live births. It is the most common cause of death in newborn infants in the western world and places a significant burden on the affected individual and their families. Previous research suggests a strong genetic component and current understanding implicates both genetic and environmental contributions to disease development. The work presented here is translational; combining laboratory, clinical and psychosocial research strategies to inform current understanding of the genetics aspects of CHD as well as patient education and support. Next generation sequencing technology was applied to individuals affected by CHD and their families. This highlighted some of the complexities of using strategies such as exome sequencing in complex disease, prompting a more targeted and clinically-applicable approach through the development of a CHD gene panel. The gene panel identified the cause of CHD in 31% of the families analysed; thereby, for the first time, offering individuals with familial forms of CHD a realistic chance at a genetic diagnosis. In addition, this work also demonstrates the benefit of individualised genetic counselling in families affected by CHD, both in terms of improving knowledge on the genetic aspects of disease as well as improving psychosocial functioning.