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.