Familial Congenital Heart Disease

Abstract

The chromosomal complement was analyzed in 35 individuals, each selected because of proven cardiac anomaly in him and in one or more of his relatives. The study to date has also been extended to include chromosomal analyses of 29 other affected and 21 unaffected relatives, a total of 85 individuals. In four of the 35 index individuals a small chromosomal variant was found, and in each case it was shown to be familial; in all, variants were detected in 11 of the 85 persons examined. The various aberrations detected-an enlarged short arm of a member of group 13-15 in two families; heteromorphic nos. 16 in one family; satellites on a no. 17 in one family -are known to exist in apparently normal individuals in the general population. Neither the biological significance of these variants nor their relation to the etiology of cardiac anomalies can be established at present. However, the following working hypothesis has been developed: Small chromosomal variations in structure are transmitted in phenotypically normal individuals in the general population and constitute the chromosomal structural load ; when the relatively infrequent but inevitable genetic imbalance of an embryo occurs as the consequence of such a chromosomal polymorphism, it may cause embryonic maldevelopment. By this mechanism, the structural load would become responsible for a proportion of birth defects.