What are the risks of congenital anomalies from consanguineous (consanguineous, meaning related by blood) marriages, specifically between first-degree relatives, such as cousins?

From the Guidelines

Cousin marriages significantly increase the risk of birth defects and genetic disorders in offspring, with first-cousin couples having approximately a 4-6% chance of having a child with a birth defect or genetic disorder, compared to about 2-3% for unrelated couples. This increased risk occurs because closely related individuals are more likely to carry the same recessive genetic mutations, which when inherited from both parents, can cause various conditions including heart defects, intellectual disabilities, metabolic disorders, and physical abnormalities 1. The closer the biological relationship, the higher the risk.

Key Considerations

• Genetic counseling is strongly recommended for related couples considering having children, as it can help assess specific risks based on family history and potentially identify carrier status for certain conditions 1.
• Prenatal testing options like amniocentesis, chorionic villus sampling, and non-invasive prenatal testing can detect some genetic abnormalities during pregnancy.
• The coefficient of inbreeding (F) provides a theoretical value for the proportion of the genome that is identical by descent (IBD) in offspring of related parents, with an average of 6.25% for first-cousin offspring 1.
• While many cousin marriages result in healthy children, the increased genetic risks should be carefully considered and discussed with healthcare providers before conception.

Recommendations

• Related couples should undergo genetic counseling to assess their specific risks and discuss potential testing options before conception.
• Prenatal testing should be considered for related couples to detect potential genetic abnormalities during pregnancy.
• Healthcare providers should be aware of the increased genetic risks associated with cousin marriages and provide appropriate counseling and testing options for related couples 1.

From the Research

Birth Defects from Breeding with Cousins

• The risk of birth defects in offspring of first-cousin matings is estimated to increase sharply compared to non-consanguineous marriages 2.
• A study in North-Eastern France found that consanguineous matings were known in 1.21% of cases with congenital anomalies, vs. 0.27% in controls, with a significant increase in malformations recorded paralleling the degree of consanguinity 2.
• The frequency of congenital malformations is higher in consanguineous couples, with a background rate of 4.5% vs. 1% in non-consanguineous couples 3.
• Consanguinity is most commonly associated with inborn errors of metabolism, which are autosomal recessive, and increases the incidence of multifactorial disorders such as diabetes, cardiovascular disorders, obesity, and certain types of cancers 3.

Reproductive Consequences of Consanguinity

• Consanguinity is practiced by up to 10% of the world's population, with rates ranging from 80.6% in certain provinces in the Middle East to less than 1% in western societies 3.
• The most significant effects on reproductive outcomes are mostly due to autosomal recessive inherited conditions and inborn errors of metabolism 3.
• Consanguinity may also affect fertility rates and increase the incidence of pregnancy wastages and preterm labor 3.

Genetic Counseling and Diagnosis

• Preimplantation genetic diagnosis (PGD) provides an alternative reproductive option for couples at genetic risk, allowing them to commence a pregnancy knowing that their baby will not be affected with the indicated genetic condition 4.
• Genetic counseling is important for consanguineous couples, as it can help identify potential genetic risks and provide options for reproductive planning 5.
• Prenatal diagnosis and genetic counseling can help identify malformations and genetic syndromes in fetuses, allowing parents to make informed decisions about the course of the pregnancy 6.