Congenital heart disease in sibships ascertained by two affected siblings

Summary Families containing at least 2 children affected by cardiologically diagnosed congential heart disease were selected from the files of the Children's Memorial Hospital, Chicago, Willis J. Potts Children's Heart Center. From the data of 54 such families a recurrence rate of CHD for additional children of between p (K=0, r_(min)=2)=0.0554±0.0256 and p (K=1, r_(min)=2)=0.0801±0.0349 was calculated. Incompleteness of families or voluntary termination of reproduction after the second affected child was born could be excluded as effective bias-inducing factors. In the great majority of cases, sibs displayed identical or closely related malformations. No paternal or maternal age effect was found. Consanguinity was not noticeably increased, but the material was unsuitable for the study of this question. A recurrence rate which was definitely higher in families with at least two affected children than in families selected by a single proband, is taken as further evidence for the importance of genetic factors in congenital heart disease. Any single-gene hypothesis can be fitted to the actual data only if far-reaching additional assumptions are made. A multifactorial genetic system explains the observations more easily. This work has been carried out in part during the author's stay at the Genetic Clinic of the Children's Memorial Hospital, Dept. of Pediatrics, Northwestern University Medical School (Prof. D. Y.-Y. Hsia, M.D.). Data have been collected in collaboration with Dr. M. H. Paul, director of the Dept. of Cardiology of the Children's Memorial Hospital, Willis J. Potts Children's Heart Center. The author was supported in part by a grant from the US Public Health Service, National Institutes of Health and a Fulbright Travel Grant.