Recurrence of Congenital Heart Defects in Families

Submitted on February 13, 2009
Accepted on May 8, 2009

Nina yen MD, MPH, DrMed^*, Gry Poulsen MSc, Heather A. Boyd PhD, Jan Wohlfahrt MSc, DrMed, Peter K.A. Jensen MD, DrMed, and Mads Melbye MD, DrMed

From the Department of Epidemiology Research (N.., G.P., H.A.B., J.W., M.M.), Statens Serum Institut, Copenhagen, Denmark; Department of Public Health and Primary Health Care (N..), Faculty of Medicine and Odontology, University of Bergen, Bergen, Norway; Center for Medical Genetics and Molecular Medicine (N..), Haukeland University Hospital, Bergen, Norway; and Department of Clinical Genetics (P.K.A.J.), Århus University Hospital, Århus, Denmark.

^* To whom correspondence should be addressed. E-mail: noy@ssi.dk .

Background—Knowledge of the familial contribution to congenital heart diseases (CHD) on an individual and population level is sparse. We estimated an individual's risk of CHD given a family history of CHD, as well as the contribution of CHD family history to the total number of CHD cases in the population.

Methods and Results—In a national cohort study, we linked all Danish residents to the National Patient Register, the Causes of Death Register, the Danish Central Cytogenetic Register, and the Danish Family Relations Database, yielding 1 763 591 persons born in Denmark between 1977 and 2005, of whom 18 708 had CHD. Individuals with CHD were classified by phenotype. We estimated recurrence risk ratios and population-attributable risk. Among first-degree relatives, the recurrence risk ratio was 79.1 (95% confidence interval [CI] 32.9 to 190) for heterotaxia, 11.7 (95% CI, 8.0 to 17.0) for conotruncal defects, 24.3 (95% CI,12.2 to 48.7) for atrioventricular septal defect, 12.9 (95% CI, 7.48 to 22.2) for left ventricular outflow tract obstruction, 48.6 (95% CI, 27.5 to 85.6) for right ventricular outflow tract obstruction, 7.1 (95% CI, 4.5 to 11.1) for isolated atrial septal defect, and 3.4 (95% CI, 2.2 to 5.3) for isolated ventricular septal defect. The overall recurrence risk ratio for the same defect was 8.15 (95% CI, 6.95 to 9.55), whereas it was 2.68 (95% CI, 2.43 to 2.97) for different heart defects. Only 2.2% of heart defect cases in the population (4.2% after the exclusion of chromosomal aberrations) were attributed to CHD family history in first-degree relatives.

Conclusions—Specific CHDs showed highly variable but strong familial clustering in first-degree relatives, ranging from 3-fold to 80-fold compared with the population prevalence, whereas the crossover risks between dissimilar cases of CHD were weaker. Family history of any CHD among first-degree relatives accounted for a small proportion of CHD cases in the population.