Congenital Heart Disease

Cardiovascular disease is the most common form of morbidity and mortality in Americans; however, it is seldom reported that nearly 57 percent of inherited disease deaths occur in people younger than 15. Heart defects that occur at birth, or congenital heart disease, are diagnosed in 32,000 infants each year in the United States. Some 300,000 individuals have congenital heart disease in this country. Heart defects are the most common congenital malformation in newborns, and for many years, we have not understood why they occur. It is a huge problem that affects millions of children worldwide, and we are now only beginning to understand the genetic basis of these disorders. Many forms of congenital heart disease have been described. In the Phoebe Willingham Muzzy Pediatric Molecular Cardiology Laboratory we are currently investigating the underlying genetic bases of Hypoplastic Left Heart Syndrome, Ebstein's Anomaly, and Heterotaxy Syndrome.

Approximately 1 percent of all children born with congenital heart disease have Hypoplastic Left Heart syndrome. In this disease, the mitral and aortic valves, which lead into and out of the left ventricle are either extremely small or impassible. The aorta, which is the main blood vessle leading out of the left ventricle, is also hypoplastic. Because blood cannot flow properly through the valves and the left ventricle, the left ventricle is underdeveloped and does not function properly.  Hypoplastic Left Heart Syndrome requires surgical correction within hours or days of diagnosis.

Ebstein's Anomaly affects the tricuspid valve of the heart, which regulates the flow of blood from the right atrium into the right ventricle. In the normal heart, the tricuspid valve is composed of three leaflets, which are precisely placed. Closure of these three leaflets during ventricular contraction forces blood into the lungs. In the heart of a patient with Ebstein's Anomaly, the three leaflets of the tricuspid valve are not located in the correct positions and do not seal properly, allowing blood to leak back into the right atrium during ventricular contraction. Most children with Ebstein's Anomaly also have an atrial septal defect which allows the oxygen-poor blood of the right atrium to improperly mix with the oxygen-rich blood of the left side of the heart. In more severe cases of Ebstein's Anomaly, the leaflets of the tricuspid valve may be displaced far into the right ventricle, resulting in a small right ventricle that does not function properly.

A normal heart can be divided into two "sides". The right side of the heart, which is composed of the right atrium and right ventricle, pumps oxygen-poor blood from the body to the lungs. The left side of the heart, which is composed of the left atrium and the left ventricle, pumps oxygen-rich blood from the lungs to the rest of the body. Patients with Heterotaxy Syndrome have malformations of the heart and blood vessels that result in the heart not having correct "sidedness". Multiple forms of Heterotaxy Syndrome have been described including patients with bilateral "right-sidedness" in which both sides of the heart (left and right) have the general appearance of being the "right" side. Patients with bilateral "left-sidedness" of the heart have the general appearance of both sides of the heart being a "left" side. Patients with "ambiguous-sidedness" have also been described. Heterotaxy Syndrome is often accompanied by other congenital malformations such as asplenia or multiple spleens.