Concerning the etiology of congenital cardiac disease

Abstract

M edicine today is involved in a massive assault on the prevention and cure of cancer and acquired heart disease, but very little effort is being expended to prevent congenital defects. Yet there are valid reasons for increasing our efforts in this area. Congenital malformations not only occur frequently, but they are important because they are often life threatening, cause a great deal of physical and psychological harm to the affected person and his family, and may be very costly in the over-all management. Clinically significant congenital defects are more common than is generally realized and cardiac malformations account for a high percentage of the total .lm4 Campbell,’ for instance, reported a 2.4 per cent incidence of major congenital malformations in a review of British families studied, and cardiac anomalies accounted for one fourth of these defects. While there are a wide variety of congenital cardiac malformations, about 85 per cent of these malformations are made up of a relatively small number of lesions. The most common lesion by far is ventricular septal defect, with a reported incidence of 20 to 40 per cent. The other common lesions are patent ductus arteriosus, atria1 septal defect, coarctation of the aorta, pulmonary valvular stenosis, aortic valvular stenosis, tetralogy of Fallot, and complete transposition of the great vessels. It is logical that the prevention of some or all of the more common lesions would therefore greatly reduce the problem of congenital cardiac defects. But to prevent congenital malformations, it is first necessary to understand their etiology and pathogenesis. While there exists a mass of information on the clinical aspects of congenital cardiac disease, very little is known about the etiology except that there are likely to be multiple factors involved.4 It is estimated that in only one fifth of these cases is the etiologic factor known or strongly suspected. The major known etiologic factors are environmental (virus infections, radiation, and perhaps drugs), and genetic (familial or hereditary, and chromosomal abnormalities). The importance of genetic factors in the etiology of congenital cardiac disease has been summarized by Campbell.’ Siblings of propositi (the affected persons) have three times (1.7 per cent) the expected incidence of congenital cardiac disease, and this rate varies with the type of lesion. There is also a strong tendency for concordance of lesions in siblings of propositi. The incidence of congenital cardiac mal-