A Clinical and Population Genetic Perspective: Risk Assessment in Case of Consanguinity

Consanguineous couples are at increased risk of having a child with a hereditary/congenital disorder. This extra risk is caused by the fact that the child can inherit the same mutated allele from both parents that originates from a common ancestor. First cousin couples are said to have 1.7-2.8% extra risk on top of the background risk that every couple has of having a child with a congenital/hereditary disorder. This extra risk entails mostly autosomal recessive disorders: disorders that only come to light when a child has inherited two mutated copies of the same gene from its parents. When both parents are carriers (i.e. only have one mutated copy) for each of their children their chance to inherit both mutated copies is 25%. The extra risk 1.7-2.8% is, however, an average percentage. In fact, only a minority of consanguineous couples has an increased risk of 25%, while the great majority of couples has a risk that is similar to that of the general population. The Netherlands, like many other Western countries, is a country where prejudices and misunderstandings about parental consanguinity in public debates are coinciding with a strong tradition of consanguineous marriage among its migrant populations. Politicians approved legislation to ban cousin marriage (De Koning et al. 2014). In the meantime, in health care, a general consensus exists that consanguineous couples should be aware of their elevated reproductive risk. There is no consensus, though, on how this can be achieved. The main objective of this thesis is to give guidance as to how the reproductive risk in consanguineous couples can be addressed in the future. Three different approaches were taken: to study the clinical genetic and population genetic perspective, the perspective of the target population and the perspective of the (primary) health care provider. The latter two focused on the situation in the Netherlands.