Congenital cardiac disease and inbreeding: specific defects escape higher risk due to parental consanguinity.

Aims: To test on a large cohort whether parental consanguinity varies among different types of congenitally malformed hearts.

Methods And Results: Between 1 May, 1999, and 28 February, 2006, a large cohort of 1585 newly diagnosed cases with non-syndromic congenitally malformed heart was enrolled at the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology, Beirut. Another group, made up of 1979 cases referred to the National Register of Paediatric and Congenital Heart Disease, but free of any malformation, and with a rate of consanguinity similar to a recent survey made by UNICEF in Lebanon, was used for the purposes of control. We used the Chi-squared test, and ratio of risk, to compare the groups. Subgroups with first degree cousins, first plus second degree cousins, and any degree of consanguinity, are significantly larger in the cohort with congenitally malformed hearts than in the control cohort, with proportions of 19.4%, 25.7%, and 27.4% versus 14.4%, 20.3%, and 23.9%, respectively. Those with tetralogy of Fallot, valvar aortic stenosis, and atrial septal defect have a significantly higher percentage of consanguineous parents than do the controls. By contrast, this is not the case for those with atrioventricular septal defect and common atrioventricular junction ("atrioventricular canal"), or discordant ventriculo-arterial connections ("transposition"). These differences persist when the types of congenital cardiac defect types are pooled according to presumed embryological processes. Those with hypoplasia of the left heart have increased parental consanguinity, but not the group of various types of discordant ventriculo-arterial connections.

Conclusion: Only some types of congenitally malformed hearts have an increased percentage of parental consanguinity, suggesting that those types with no increased risk due to parental consanguinity are determined by genetic factors that are X-linked or exclusively autosomal dominant.