22 June 2008
Department of Public Health, University of Oxford.Appeared in BioNews 463
In children of unrelated couples, the risk of congenital and genetic including recessive problems is usually estimated at about 2-3 per cent. First cousins have a higher risk of recessive problems in children than unrelated couples because they share 12.5 per cent of their genetic material and may have inherited the same mutation from a common ancestor. Risk to their children is usually estimated at about double the risk of congenital and genetic problems in children of unrelated couples. At about 4-6 per cent, this doubled risk is also a 94-96 per cent chance that their child will be perfectly healthy. A cousin couple is thus more likely to have a healthy child than to have a child with a recessive problem.
Risk for recessive conditions also varies between communities depending on the distribution of recessive mutations, making some conditions more common than others, and on the history of marriages to blood relations within them. In the UK, cousin marriage is no longer common in the majority population but is practised within quite diverse minority groups, particularly those of relatively recent migrants from the Middle East and South Asia. Debate has focused on British Pakistanis, the largest population practising cousin marriage, because of the comparatively high incidence of a range of serious recessive problems.
In some British Pakistani families, marriage within the family or extended kinship group has been practised for generations and first cousin couples can trace numerous additional blood ties in their family history. They may therefore share more than 12.5 per cent of their genetic material and have a higher risk for recessive problems in their children than if they were first cousins without any additional connections by blood. This is the most likely explanation for the observation that, in some sections of the British Pakistani population, the risk of death or serious disability in children may be as high as 10 per cent.
Marrying an unrelated person does not remove this risk because of the general population risk of two people carrying a mutation in the same gene, particularly for the more common recessive conditions, but it can significantly reduce risk for rare recessives. In managing recessive risk for individuals or couples, the critical thing is not so much whether or not they are blood relatives but whether or not they are carriers of a mutation for the same condition. Premarital or pre-conception genetic counselling can be useful to establish a couple's risk and reproductive options before they start a family, particularly where one or both partners have an affected relative or if one partner has a recessive conditions themselves.
In the UK today, it would be as inappropriate to castigate cousin marriages on grounds of elevated recessive risk as it would be to stigmatise late childbearing on grounds of elevated risk of chromosomal abnormalities. Down syndrome risk is now managed through generic prenatal screening and counselling. Recessive risk presents rather different challenges because it includes risk for many different, mostly rare, conditions, some of them treatable. Carrier and prenatal tests are now possible for an increasing number of recessive conditions but screening for them all it not currently possible or realistic. It is often only after the birth of an affected child that clinicians know which condition is relevant within any particular family.
Recessive risk need to be managed by improving awareness of it, including the elevated risk associated with marrying relatives such as first cousins where there is a history of marriage within the family, and by ensuring appropriate genetic counselling. Public health and genetic counselling provisions should strive to enable individuals and couples to make informed marital and reproductive decisions, wherever possible. Any couple worried about genetic risk to children should ask their GP for a referral to a genetics clinic. Some scientists think that in the next decade or so we may all have access to our own personal DNA results and will each consequently know much more about the mutations we all carry.