Etiologic relations among categories of congenital heart malformations

Pairs of siblings with congenital heart malformations of different types were analyzed for evidence of nonrandom association of defects within families that might suggest a genetic predisposition common to two or more kinds of malformations. An excess of pairs was noted for tetralogy of Fallot and pulmonary stenosis, tetralogy of Fallot and transposition of the great vessels, and tetralogy of Fallot and ventricular septal defect, thus suggesting that there may be a developmental relation between these lesions. This finding is supported by a recent study in the Keeshond dog demonstrating a genetic predisposition common to tetralogy of Fallot, pulmonary stenosis and ventricular septal defect. Thus the method does seem capable of revealing etiologic relations, probably genetic, among different types of cardiac lesions. Data on risks of recurrence for siblings of children with these defects will now have to be refined to take into account the possible recurrence of related lesions.