Complete transposition of the great arteries - Patterns of congenital heart disease in familial precurrence

Background-Transposition of the great arteries (TGA) is considered to be as sociated only rarely with genetic syndromes and to have a low risk of precu rrence among relatives of affected patients. Because most family studies ha ve involved a relatively small number of patients and evaluated all types o f TGA as a single group, we performed a large, prospective study investigat ing the precurrence of congenital heart disease in families of children wit h complete, nonsyndromic TGA. Methods and Results-From January 1997 through December 2000, 370 patients w ith nonsyndromic, complete TGA were consecutively evaluated and enrolled in the study. The occurrence of cardiac and noncardiac anomalies among relati ves of the probands was investigated. Relatives with congenital heart disea se were found in 37 of 370 families (10%), including 5 of 37 families (13.5 %) with more than one affected relative, TGA itself was the most common pre current malformation: complete TGA occurred in 6 families and congenitally corrected TGA occurred in 5 families. Precurrence risks for congenital hear t disease were calculated at 1.8% (8 of 436) for siblings, 0.5% (4 of 740) for parents, 0.5% (16 of 3261) for first cousins, 0.2% (4 of 2101) for uncl es/aunts, and 0.06% (1 of 1480) for grandparents. Conclusions-The present study shows that TGA is not always sporadic in fami lies. Precurrence of concordant cardiac defects within affected family memb ers supports monogenic or oligogenic inheritance of TGA in certain kindreds . Moreover, the occurrence of complete TGA and congenitally corrected TGA a mong first-degree relatives in several different families strongly suggests an underlying pathogenetic link between these 2 malformations that has bee n previously unrecognized.