Trisomy 22 is a genetic condition characterized by the presence of three copies of chromosome 22 in a person’s cells, instead of the expected two. This condition is overwhelmingly lethal early in development, making live birth extremely rare, occurring in approximately 1 in 30,000 to 50,000 births. The causes of this condition are rooted in different genetic events, which determine the severity and the type of trisomy that develops.
The Primary Cause Nondisjunction
Nondisjunction, the failure of proper chromosome separation, is the most frequent cause of Trisomy 22. This error typically occurs during meiosis, the specialized cell division that produces reproductive cells. Normal meiosis ensures that each reproductive cell receives exactly one copy of each chromosome.
When nondisjunction occurs, the dividing cell fails to distribute the chromosomes evenly. This results in a gamete that carries two copies of chromosome 22 instead of the necessary single copy. If this abnormal cell then fuses with a normal gamete, the resulting embryo will have three total copies of chromosome 22 in every cell.
Approximately 90% of these errors happen during Meiosis I, the first stage of egg cell division. Since the majority of errors originate in the egg, advanced maternal age is a factor associated with a higher incidence of the condition. The resulting genetic imbalance often makes the embryo nonviable.
How Timing Determines Full Versus Mosaic Trisomy 22
Full Trisomy 22 occurs when the gamete already carries two copies of chromosome 22, resulting from the meiotic error before fertilization. In this scenario, every cell of the developing embryo contains three copies of the chromosome. This complete form is highly lethal, with survival typically limited to only a few days after birth.
Alternatively, the condition can arise from a nondisjunction event that happens after fertilization, during the early mitotic divisions of the developing embryo. This later mitotic error results in Mosaic Trisomy 22, where only a percentage of the body’s cells carry the extra chromosome 22. The remaining cells maintain the typical two copies, which can mitigate the severe effects associated with the full form.
The clinical outcome for individuals with the mosaic form varies widely, directly dependent on the proportion of trisomic cells and which tissues are affected. Mosaic Trisomy 22 is compatible with prolonged survival and a much broader spectrum of health outcomes.
Structural Causes and Partial Trisomy 22
Partial Trisomy 22 means that only a segment of chromosome 22 is triplicated, not the entire chromosome. This situation arises from a specific type of chromosomal rearrangement known as a translocation. A translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome.
In the case of a parental balanced translocation, a parent’s chromosomes are rearranged, but the total amount of genetic material is correct, meaning they are typically unaffected. However, during the formation of their gametes, this rearrangement can be passed on in an unbalanced way. When the offspring inherits the rearranged chromosome, they receive an extra piece of chromosome 22, leading to the partial trisomy.
The resulting partial trisomy is less common than the full form but can lead to a recognizable syndrome depending on the size and location of the duplicated segment.
Biological Factors Influencing Incidence
The likelihood of a nondisjunction event occurring is influenced by certain biological factors, most notably the age of the mother. As a woman ages, the quality of the egg cells declines, increasing the risk of errors during the meiotic division process.
The risk of having a child with Partial Trisomy 22 is directly linked to whether either parent carries a balanced translocation. The presence of the rearrangement means there is a specific, measurable recurrence risk for an unbalanced pregnancy in future conceptions. Genetic counseling can help determine the exact nature of the parental translocation and the probability of having another affected child.