The genetics of congenital heart disease and situs inversus in sibs.

There have been many reports of the same or similar congenital malformations of the heart in two sibs or in a child and parent. Abbott (1927) found 11 such pairs and Brown (1939) who had seen six pairs thought they were most common in members of the same generation. Medvei and Rosler (1932) collected 37 families with such pairs and Gansslen et al. (1940) 68 families: the diagnoses made at that time can not now be accepted as certain without necropsy proof and this was available only in a minority. Campbell (1949) reported four pairs and mentioned some others more briefly. Since then several have been reported and a great many have been seen. However, few large series have been reported, so our 40 families seem worth recording. Of these pairs, 26 were sibs, 9 were parent and child, and 6 were less close relatives, one family (F26) being included in both the first groups, as a woman and her son were certainly affected and probably her brother and her father. There were six other families with more than two members affectedthree sibs in four (F3, 6, 11, and 35), an uncle as well as two sibs in one (F8), and a grandmother as well as a mother and daughter in one (F34). There was less decisive evidence of a third member being affected in two others (F26 and 29). Generally the malformations found were the same or similar in both members of the pair (concordant) but sometimes they were quite different (discordant). It is important for a clinician to emphasize that it is not very common for two children with congenital heart disease to be born in one family. The parents of a child with a congenital malformation should not be deterred from having another child by the fear that it will be abnormal for this is not very likely. It is certainly more likely than would be expected by chance, but these 40 exceptions have been found among about 2000 families with a case of congenital heart disease-an incidence of 2 per cent. Polani and Campbell (1955) made a statistical enquiry into the families of 396 patients, mostly with Fallot's tetralogy, and found the incidence of congenital heart disease among the sibs born after the propositus was between seven and twenty times as large as would be expected by chancetwenty times as large, 2 per 100 instead of 1 per 1000, taking the number who were alive at the age of ten years, or seven times as large taking the figure that includes all children born alive with congenital heart disease.