Maternal transmission of congenital heart diseases: new recurrence risk figures and the questions of cytoplasmic inheritance and vulnerability to teratogens

Abstract

A review of 8 studies involving 3,996 offspring of parents who have congenital heart disease revealed that the risk for all defects was substantially higher if the affected parent was the mother rather than the father. The risk ratio ranged from a high of 6.39 for aortic stenosis to a low of 1.48 for patent ductus arteriosus, and the ratio was statistically significant in aortic stenosis (p = 0.025) and ventricular septal defect (p less than 0.001). Despite the relatively large number of cases, there were still too few patients to reveal statistical significance for a malformation such as atrioventricular canal, in which there were 5 affected offspring among 36 children of mothers who had atrioventricular canal and no affected children among 16 offspring of affected fathers (p = 0.12). The possible reasons for the preponderance of affected offspring of mothers with a congenital heart disease was studied in the context of various modes of inheritance and maternal physiology. The preliminary conclusion is that although many familial cases of congenital heart disease are compatible with multifactorial inheritance and vulnerability to teratogens, an important subset of cases, particularly in some high-risk families, may be better explained by cytoplasmic inheritance than by multifactorial or mendelian modes. Current genetic counseling should take into account the differences in risk to offspring of affected mothers while confirmation and further investigation proceeds.