FACTORS IN THE AeTIOLOGY OF ATRIAL SEPTAL DEFECT

Abstract

We have made enquiries about the families of 170 patients with atrial septal defect for genetic or environmental factors that might help to explain its etiology. Many of our patients (16%) had also other malformations of the heart, but generally these were less important. Some had non-cardiac malformations as well. A congenital malformation of the heart, most often an atrial septal defect, was found more often than would be expected by chance in the sibs of our propositi with atrial defect (1.1%) their parents (1.3%). Many sibs, perhaps more than would be expected, had also non-cardiac malformations (2.1%). The parents of the propositi were first cousins more often than would be expected (1.9%). This suggests that some of the cases are due to recessive Mendelian inheritance. When two members of a family each have an atrial septal defect, they are almost equally likely to be a parent and child or two sibs. In some families there is good evidence of dominant Mendelian inheritance with incomplete penetrance. We think that these two mechanisms could explain only a proportion of cases and that environmental factors also are of importance. Mean paternal age exceeded mean maternal age by 3.03 years, which is more than the normal difference (2.3 years) and may point to a genetic error, at least in some cases. Neither maternal age nor birth order were proved to have any effect on the incidence of atrial septal defect, but there were several firstborn children of mothers of 35 and over and we think this is worth further investigation. As in most reported series, there were more girls and women than boys and men, the ratio being 1.7:1. The sex incidence was more nearly equal in the first decade, but the reason for this is not clear. Both boys and girls with atrial defect were a little lighter at birth than their normal sibs, particularly the boys. More boys with atrial septal defect were born in January and February and the excess was enough to make the births in the first quarter about double the births in the other three quarters. There was no difference in the quarterly incidence of births for the girls.