Genetic Approach to Consanguineous Marriages

In many parts of the world, consanguineous marriages are commonly seen due to cultural, social, or economic reasons. The frequency of anomalies in babies born from consanguineous marriages is higher compared to the general population. Therefore, it is especially important to evaluate consanguineous marriages not only from a cultural perspective but also in terms of health and genetics. In these marriages, since both parents have a higher chance of carrying the same defective genes inherited from their ancestors, the risk of certain hereditary diseases appearing in the child increases.

On average, 4-7% of newborns have a physical or mental disability. About 20% of these disabilities are hereditary, meaning they are inherited from the mother and father. Moreover, more than half of these disabilities occur in children born from consanguineous marriages.

According to the 2016 data from the Turkish Statistical Institute, the rate of consanguineous marriages in Turkey is 23.2%. This rate, which can reach up to 40% depending on the region, is above the world average. The global average is approximately 8%. However, with the advancement of modern medicine and genetic science, it has been scientifically proven that consanguineous marriages carry certain genetic risks. Especially in marriages between first-degree cousins, the risk of genetic diseases being passed on to children significantly increases.

According to data from the World Health Organization (WHO), congenital anomalies are detected in 3 out of every 100 children born in the general population due to various causes. This risk approximately doubles in couples who have consanguineous marriages.

Do couples who have consanguineous marriages always have children with anomalies?

If a couple in a consanguineous marriage carries a defective genetic trait inherited from common ancestors, the chance of this type of disease occurring is 25%. In pregnancies resulting from first cousin marriages, the risk of having a child with an anomaly is approximately between 3-5%.

Genetic Tests Conducted in Consanguineous Marriages

• Commonly Screened Diseases: Thalassemia (Mediterranean Anemia), Spinal Muscular Atrophy (SMA), Cystic Fibrosis, Phenylketonuria (PKU), Duchenne Muscular Dystrophy (DMD), Congenital Adrenal Hyperplasia, some metabolic diseases
• Molecular Genetic Tests: If there is a known genetic disease in the family, specific genes related to that disease can be examined at the molecular level.
• Broad Panel Genetic Screening: Tests performed with Next-Generation Sequencing (NGS). Panels screening hundreds or even thousands of hereditary diseases allow for a more comprehensive analysis.
• Prenatal (During Pregnancy) Tests: If pregnancy has started and the couple are carriers:
  • Amniocentesis (after 16th week)
  • Chorionic Villus Sampling (CVS) (11th–13th weeks)
  • Non-invasive Prenatal Test (NIPT): The baby’s DNA can be analyzed from the mother's blood

What is Whole Exome Sequencing (WES) Test?

Whole Exome Sequencing (WES) in consanguineous marriages stands out as an important screening and diagnostic tool for genetic disease risk. This is because couples in consanguineous marriages have a higher likelihood of sharing common genetic heritage, which increases the risk of autosomal recessive diseases appearing in their children. Whole Exome Sequencing (WES) is a genetic testing method that examines most of the protein-coding regions called exons in a person’s DNA. It can detect about 7,000 genetic diseases caused by approximately 23,000 genes in the genome. WES is the best method to apply for detecting non-specific genetic diseases.

Why is WES Important in Consanguineous Marriages?

Both parents may be carriers of the same disease gene. In this case, there is a 25% chance that their child will inherit the disease. Most of these diseases are rare and may not have been previously observed in the family. WES can detect these rare and unexpected genetic diseases.

Who Should Take the WES Test?

This test can be applied to any couple who requests it, but it is primarily recommended for the following couples:

• Couples who have previously had a pregnancy diagnosed with a genetic disease or have children with genetic diseases
• Couples in consanguineous marriages
• Couples known to carry genetic diseases in their family
• Cases of pregnancy losses or stillbirths with anomalies
• For Diagnostic Purposes (if there is a disease): If the child has unexplained conditions such as developmental delay, neurological symptoms, muscle diseases, or metabolic disorders, WES can help find the cause.
• For Carrier Screening (before marriage or pregnancy): To determine whether both partners carry the same genetic disease.
• Family Analysis (Trio analysis): When done together on mother, father, and child, the inheritance pattern of disease-related variants can be understood more clearly.

Couples planning to have a child through IVF can also take this test if they wish. This way, they can learn about possible genetic diseases they might carry. If any carrier status or mutation is detected through this test, Preimplantation Genetic Diagnosis (PGT) is strongly recommended for the patient undergoing IVF. This method allows the selection and transfer of healthy embryos, increasing the chance of having a healthy child.

Genetic Diseases That Can Occur in Consanguineous Marriages:

Autosomal recessive diseases: These diseases are associated with the risk of occurring in children of two carrier individuals. For example: Mediterranean anemia (thalassemia), cystic fibrosis, spinal muscular atrophy (SMA), phenylketonuria, and some metabolic diseases.

Congenital anomalies: Problems such as heart diseases, mental and physical developmental delays may occur. Risks seen in consanguineous marriages also include stillbirth, miscarriage, and neonatal loss.

Are There Precautions for Consanguineous Couples to Have Healthy Children Regarding Hereditary Diseases?

One of the most important points to remember is that couples planning consanguineous marriage should consult the nearest Medical Genetics department before marriage and receive genetic counseling where the information mentioned above will be reviewed. If hereditary diseases are detected in the family as a result of genetic evaluation, embryos of genetically at-risk couples can be examined with Preimplantation Genetic Diagnosis (PGT) before pregnancy occurs, and healthy embryos can be selected. With this method, healthy pregnancies can be achieved by transferring embryos found to be normal to the mother. For single-gene diseases that have the potential to pose a life-threatening risk, prenatal diagnostic methods such as amniocentesis or chorionic villus sampling can be used to determine whether the baby is affected.

For more detailed information, you can reach us via WhatsApp at +90 530 886 52 63 or by phone at +90 224 251 50 00 to make an appointment and have a detailed consultation with our Genetics Specialist.