8.9 The clinical approach for consanguineous marriage
In advising related couples, or relatives who wish to marry, a geneticist always first draws up a detailed family tree. Families may then be seen to fall into two groups. The first and largest group consists of related couples who know of no evidence of a genetic disorder in the family. These couples may be informed of the observed average additional genetic risk associated with cousin marriage. In the industrialized world, most related couples who consult a clinical geneticist are planning to marry or are already married. There are no published reports on their subsequent choices, but the impression is that most find the genetic counselling reassuring, and proceed to marry and set up a family. Clear information on this point is particularly important in the Eastern Mediterranean Region, since so many families are involved.
The second, smaller group are those where it seems that a family member may have, or may have died from, a genetic disease. Investigations are then carried out to establish the true diagnosis, if possible. Often the condition in question proves to have a negligible recurrence risk, e.g. Down syndrome or a neural tube defect, or not to be inherited, e.g. a disorder due to a new mutation like osteogenesis imperfecta. In such cases the couple can be appropriately reassured.
If the relative does in fact suffer from a dominant, X-linked or recessively-inherited disorder, it may be possible to offer the couple carrier testing. They can then make a decision about whether to marry, or to have children, on the basis of definite information. Even when carrier testing is not possible, if the inheritance pattern is clear, the couple can be informed of their statistical risk of having children with the disorder in question. Figure 8.1 shows two examples of how such risks can be calculated for a recessively-inherited disorder,whether for relatives of an affected individual or of a carrier detected, for example, by population screening.
Example 1. Uncle or aunt has a recessively-inherited disorder
Example 2. Sibling of one partner has a recessively-inherited disease
Figure 8.1 Calculation of genetic risk of consanguineous couples from family history
Example 1. Unce or aunt has a recessivley-inherited disorder
Once a single gene disorder has been diagnosed within a family, over 50% of close relatives will also be carriers (see Table 7.1). It is, therefore, basic genetic practice to offer genetic counselling (and carrier testing when this is feasible) to as many family members as possible. The same approach is indicated whether consanguineous marriage is common or rare, so genetics services can be developed without undue emphasis on particular marriage patterns. This may be advantageous when efforts to discourage consanguineous marriage have created some popular confusion about the concepts of genetic counselling.
However, in principle, a convention of cousin marriage could make family-oriented genetic counselling particularly effective, for two main reasons. First, unusually large numbers of carriers of the presenting disorder may be detected within the family. Carrier testing may, for example, permit early detection of many individuals at risk for some conditions (such as family cancer syndromes) where surveillance and early treatment could be beneficial.
Second, when cousin marriage is common within the family, carriers of recessive disorders are at particularly high risk of making an at-risk marriage. Many carriers will already be married and some couples at risk may be identified in time for prospective reproductive counselling. Many will be children or not yet married, and early information on carrier status may be taken into account to avoid further at-risk marriages within the family.
Detection of a carrier by population screening also identifies a family at high genetic risk who could appropriately be offered extended family studies.
There is as yet very little published research on strategies for genetic counselling in the Eastern Mediterranean Region. A range of information is needed about the potential of a family-oriented approach, and common recessively-inherited disorders like thalassaemia and sickle cell disease (where carrier detection is feasible and cheap) provide a convenient model. Studies of a limited number of families with an affected child would allow calculations of the proportion of carriers and couples at risk who could theoretically be detected by extended family studies. The same research studies might also show what proportion of families would welcome extended family studies, and their views about how they could best use information on reproductive risk. A family-oriented approach is labour-intensive, but an analysis of costs and benefits is needed as it might yield exceptional benefits in an Eastern Mediterranean Region setting.
Even if it becomes clear that the regional kinship structure offers exceptional opportunities for effective genetic counselling, these can be exploited only if there are adequate genetic diagnostic facilities, and trained genetic counsellors who have the confidence of the population. The question therefore arises of how the limited existing resources can be used most efficiently. One possible policy may be to systematically encourage the earliest possible diagnosis of affected children, followed by genetic counselling for the extended family. The approach has important implications for paediatric services. Paediatricians need:
• Support in further developing their genetic diagnostic skills.
• Access to genetic laboratory services, including chromosome, DNA and biochemical studies, and postmortem diagnosis.
• The assistance of trained associate genetic counsellors, e.g. nurses, for taking genetic family histories, drawing pedigrees and providing genetic counselling for the numerous families who need it. Training courses for such genetic counsellors would need to be developed at an early stage.