Definition: Consanguinity means descent from a common ancestor; a consanguineous couple is usually defined as being related as second cousins or closer. The word derives from ‘con’+ ‘sanguine’ – from the Latin, meaning ‘of the same blood’.
History
Consanguineous marriage has been a part of most societies as far back as the Old Testament of the Bible – Leviticus 18 provides instructions about which relatives cannot marry. Famous first cousin couples include Charles Darwin and Emma Wedgwood, and Albert Einstein and Elsa Einstein. However, in the late nineteenth and early twentieth century, as the study of genetics began in earnest, the question of the increased risk of medical problems in the offspring of such unions was raised, and more recently the prevailing attitude particularly in the USA has been disapproval of marriage to close relatives.
In English law, the Marriage Act 1949 sets out a schedule of prohibited marriages. Interestingly cousin marriages are not prohibited in English Law.
Social Aspects
Consanguineous marriage today is most prevalent in communities originating from North Africa, the Middle East, and large parts of Asia. In the British Pakistani community it is estimated that 50-60% of marriages are consanguineous, and there is evidence that this proportion is rising. Geographical or social isolation of migrant groups may play a part in this. In addition, such populations may have a degree of inbreeding due to many generations of marriage within the community, even in couples who are not formally consanguineous.
First-cousin marriages are the most common, but closer relationships such as double first cousins also occur.
Reported benefits of consanguineous marriage include:
-
Keeping property and money within the family
-
Staying within a well-understood family unit
-
Improving the position of women by decreasing the chances of maltreatment from a husband bound by family ties
The main perceived disadvantage is the (frequently exaggerated) worry about offspring risks, but anxiety about social stigma and difficulty living an autonomous married life separate from the wider family have also been reported. It is important for consanguineous couples to encounter open and non-judgemental attitudes to their relationship from the medical profession, to enable steps to be taken at individual and population levels to decrease morbidity and mortality while avoiding disruption of traditions and social norms.
Genetic Aspects
The population risk for any couple of having a child with a serious or lethal medical condition is around 2% (1 in 50). The excess risk for a couple who are related as first cousins, in the absence of a known genetic disease in the family, is in the order of 3% (1 in 30). This fact often comes as a relief to couples who expect a significantly higher figure.
The excess risk is as a result of autosomal recessive conditions arising due to homozygosity by descent – that is, the risk of a recessive mutation present in an ancestor being passed down 2 branches of the family, and coming together in the consanguineous marriage. It is thought that we all carry at least one mutated allele which would cause an autosomal recessive condition if present in two copies (homozygousity). If this mutant allele is passed down to both members of a consanguineous couple from a shared ancestor they will both be carriers for this condition, and will therefore have a 1 in 4 chance of having an affected child.
The chance of both parents being carriers for a recessive condition is determined by how closely they are related, which means that the offspring risks can be minimised while retaining the social benefits of consanguinity if marriages occur between more distant relatives (e.g. second rather than first cousins).
Pre-marital Counselling
Some consanguineous couples or their families ask for pre-marital advice to make an informed decision about their offspring risks. Such requests may be referred directly to the Regional Genetics Service, where non-directive counselling will be offered to explain the mechanisms of autosomal recessive inheritance and the specific risks for that couple. A full three-generation pedigree will also be taken in search of possible autosomal recessive conditions, and carrier testing can be arranged for conditions known to be common in the relevant ethnic group.
If there is a family history of a possible autosomal recessive condition, this may increase the offspring risks considerably over the background risks of consanguinity. If there is a known mutation in the family, the couple can be tested for their carrier status and prenatal diagnosis offered if required. If the diagnosis or mutation is not known, investigation of an affected relative may be possible. Otherwise, an estimate of the risks involved and detailed fetal scans (if appropriate) are the only option, and this leaves many couples feeling disturbed at the remaining uncertainty.
If an affected child dies, or an affected pregnancy is terminated, a post mortem examination will be suggested, as this represents the best chance to make the diagnosis and identify the causative mutation. While of course this is a stressful topic to raise with grieving parents, and there may be religious objections. However, it is important that all couples and their advisors understand that a post mortem is being offered in the hope that it may enable their doctors to tell whether their next child might be affected by the same condition.
It can be extremely frustrating for a couple if, in a future pregnancy, the lack of information about their first child makes it impossible to provide accurate advice and testing.
Clinical Presentations
When an abnormality or illness presents in the child of a consanguineous couple, investigations and referrals should proceed as clinically indicated for the presenting symptoms, but with an emphasis on autosomal recessive conditions in the differential diagnosis. However, it is important to remember that most childhood illness in consanguineous families is unrelated to the consanguinity, and autosomal recessive conditions (particularly the more common ones) may arise by chance in consanguineous couples, with the child having two different mutations. If this can be proved, it can help parents to know that their consanguinity is not responsible for the condition.
It is important to have a high index of suspicion for inborn errors of metabolism in children of consanguineous parents, as most of these conditions are inherited in an autosomal recessive manner, and while individually rare, collectively they represent a significant burden of disease, including some conditions which are treatable if caught at an early stage. A number of recessive genes cause prelingual deafness, and it is important for babies of consanguineous parents to receive their routine hearing tests.
Aside from autosomal recessive conditions which cause learning difficulties, consanguinity does not have any effect on intelligence, and there is no evidence that consanguinity affects fertility or adult health. Consanguineous couples with a child with an undiagnosed medical condition have a higher chance than unrelated couples of future children being affected, due to the possibility of an unrecognised autosomal recessive condition.
