Life Lines 47

NEW INSIGHTS INTO THE ORIGIN OF CONGENITAL HEART DISEASE



Congenital heart disease is one of the more common forms of birth defects. With estimates running from 19 to 75 cases per 1000 births depending on what heart conditions are included. Cardiologists usually classify such babies as having one of three types of disorders. The first involve “cyanotic” or blue baby conditions associated with the blood vessels in the heart. The second involve defects of the left ventricle and its supporting valves. The left ventricle pumps blood through the aorta to the rest of the body. The third involves “septation defects” which we usually think of as holes in the inner walls of the heart separating the chambers from each other.

My brother Roland (1929-1975) was born with a congenital heart defect that limited his activities growing up. In those days in elementary school the sick kids were put in a “sunshine class.” This exempted them from gym and going up steps to other classrooms. My brother never married. He worked initially as a “printer’s devil” for a Swedish -American newspaper (Nordsjörnan) in New York, then as an elevator operator, then as an illustrator at UCLA, and finally as a graphic artist for the Nielsen ratings company. He was a much-loved uncle always enjoying a game of chess with his nephews and nieces and never failing to visit without bringing some candy to distribute. As a child, I used to listen to the thumping of his heart. It enlarged over the years and he had the bluish lips and clubbing of fingers associated with advanced heart disease. He appreciated the years he had lived because at birth our mother was told he would probably die within six months. There was no surgery available in the years of his youth.

The molecular biology of the heart is being worked out. Genes for two embryonic tissues that form on days 15-32 of pregnancy produce a crescent shaped sandwich of two layers that differentiate into the future left ventricle and aorta from the first heart field and the right ventricle and two atrial chambers that form from the second heart field. That process takes place during the first trimester of pregnancy (roughly to about 90 days after fertilization). These genes can be studied in mice to see how they produce these cardiac defects. While there are specific genes involved in heart defects, the genetics is still complex, with different types of abnormalities among the relatives instead of a consistent fidelity to one of the three original forms of malformation. No one knows why this variation in expression exists.

One of the surprising findings for cardiologists is the outcome of childhood surgery for these defects. It certainly extends life expectancy and gives some degree of normalcy in blood flow and oxygen-carrying capacity to these infants and children, but in their mature life there is a much higher risk for a different heart disease (an enlargement and failure of cardiac muscle) but cardiologists still don’t know why that occurs and thus the importance for them to study this in mouse models of human cardiac defects. Almost all of these genetic and molecular aspects of congenital heart defects have been worked out in the past ten years so this is a rapidly evolving field of human biology and medicine.