Down Syndrome, also known as Trisomy 21, is a genetic condition caused by the presence of a full or partial extra copy of the 21st chromosome in the body’s cells. This genetic occurrence can affect one or both fetuses in a twin gestation. The probability and mechanism differ significantly between identical and fraternal twins, and the specifics of who is affected depend entirely on the type of twin pregnancy.
Understanding Down Syndrome and Twin Types
The underlying cause of Down Syndrome in approximately 95% of cases is an error in cell division called nondisjunction, which results in the extra copy of chromosome 21. This event typically happens randomly in the egg or sperm cell before conception, leading to a fertilized egg with 47 chromosomes instead of the usual 46.
Twins are classified into two main types based on their genetic origin. Identical, or monozygotic, twins develop from a single fertilized egg that splits into two embryos early in development, giving them nearly identical genetic material. Fraternal, or dizygotic, twins result from two separate eggs fertilized by two different sperm cells, making them genetically no more alike than any other siblings born at different times.
Down Syndrome in Identical Twins
Since identical twins originate from the same single fertilized egg, they share the exact genetic makeup, including the full complement of chromosomes. If the initial egg was fertilized with the extra chromosome 21, both twins are expected to have Down Syndrome, a situation referred to as concordance. The condition is present from the start, affecting all cells as the single zygote divides and then splits into two embryos.
There is a rare exception where one identical twin has Down Syndrome while the other does not, resulting in a discordant pair. This discordance typically occurs because of a post-zygotic mutation, meaning the error happens after fertilization and after the initial splitting of the single egg. One possibility involves mosaicism, where the error in cell division occurs later, leading to one twin having a mixture of cells with and without the extra chromosome 21.
Down Syndrome in Fraternal Twins
Fraternal twins result from two completely independent fertilization events. Because of this genetic independence, the risk of Down Syndrome in one fraternal twin is completely separate from the risk in the other. It is possible for one fraternal twin to have Down Syndrome while the co-twin is unaffected. This discordant outcome is the most frequent scenario observed in fraternal twins.
The risk for each fraternal fetus is calculated based on the same factors as a singleton pregnancy, most notably the age of the mother at conception. The risk is applied independently to each of the two fertilized eggs. While the overall chance of having at least one affected twin is slightly higher than in a singleton pregnancy, the probability of both twins being affected is low, as it requires two separate, independent nondisjunction events to occur.
Screening and Diagnosis in Twin Pregnancies
Prenatal screening for Down Syndrome in a twin pregnancy presents unique technical challenges. Non-Invasive Prenatal Testing (NIPT), which analyzes cell-free DNA from the placenta circulating in the mother’s blood, is a highly effective screening tool. However, in a twin pregnancy, the NIPT result provides a single risk assessment for the entire pregnancy. The presence of two different fetal DNA sources can slightly lower the accuracy, particularly in dizygotic twins where only one is affected.
Other screening methods, such as the combined test involving a nuchal translucency ultrasound and maternal blood markers, also provide a risk assessment for the overall pregnancy. If a screening test indicates a higher chance of the condition, a diagnostic procedure is offered to confirm the presence of the extra chromosome. Invasive diagnostic tests, such as amniocentesis or Chorionic Villus Sampling (CVS), require sampling from each fetus’s gestational sac separately to determine which twin is affected. These procedures carry a higher technical difficulty and risk of miscarriage in a twin pregnancy compared to a singleton pregnancy.