Cardiovascular disease associated with genetic defects

Background

Numerous genes affect cardiac morphogenesis and are implicated in congenital heart diseases. Some genetic mutations are associated with problems involving the respiratory tract, kidneys, brain, and immune system, which may affect morbidity and mortality. Therefore, proper identification of genetic disease is important.

Aim of review

The purpose of this article is to review cardiac embryology, common forms of congenital heart disease that may occur from disruption of embryologic development and common genetic defects that may cause malformations and clinical syndromes.

Key scientific concepts of review

During embryologic development, a heart tube is formed early in gestation and folds on itself. Proper heart looping and lateralization rely on specific patterning pathways. A defect in the right-left patterning pathways may cause heterotaxy. Heart septation subsequently partitions the heart into the four cardiac chambers. Disorders of heart septation include atrioventricular septal defects, which are associated with Down syndrome. During conotruncal development, the outflow tract separates into the pulmonary trunk and aorta. Failure of normal conotruncal development may cause truncus arteriosus, tetralogy of Fallot, coarctation of the aorta, or interrupted aortic arch. Truncus arteriosus may be associated with DiGeorge syndrome, CHARGE syndrome, or VACTERL association. Tetralogy of Fallot is associated with DiGeorge syndrome and mutations in NOTCH1. Coarctation of the aorta is associated with Turner syndrome, and interrupted aortic arch is associated with DiGeorge syndrome. Genetic testing is important in patients who have CHD and may help predict extracardiac disease and prognosis. Geneticists and genetic counselors are important in this process.