Trisomy 22 is a severe chromosomal condition caused by the presence of an extra copy of chromosome 22 in a person’s cells. This genetic alteration results in three copies of the chromosome instead of the usual two. Complete Trisomy 22 is incompatible with life, often leading to spontaneous miscarriage during the first trimester of pregnancy. For the rare cases of live birth, the condition results in severe congenital issues, including cardiac abnormalities and developmental delays.
Understanding Human Chromosomes
Chromosomes are thread-like structures found in the nucleus of every cell that contain the blueprint for human life. Humans typically have 46 chromosomes, organized into 23 pairs: 22 pairs of autosomes and one pair of sex chromosomes. Each pair consists of one chromosome inherited from each parent, resulting in two copies of each chromosome.
Trisomy means an individual possesses three copies of a particular chromosome instead of the normal two. Chromosome 22 is the second smallest autosome, containing hundreds of genes that provide instructions for proteins involved in neural development, cell signaling, and immune response. An extra copy of this chromosome significantly disrupts the genetic balance required for typical development.
Errors in Cell Division
The primary cause of Trisomy 22 is nondisjunction, a failure in cell division meaning “not coming apart.” This error occurs during meiosis, the specialized process that creates egg and sperm cells (gametes). Meiosis ensures each gamete receives one copy of each chromosome, so the resulting embryo has the correct total of 46 chromosomes upon fertilization.
Nondisjunction can happen during two phases of meiosis, Meiosis I or Meiosis II, both leading to an abnormal gamete. If the error occurs in Meiosis I, homologous chromosomes fail to separate, resulting in a gamete that contains two copies of chromosome 22. If the error happens in Meiosis II, the sister chromatids fail to separate, also producing a gamete with two copies of chromosome 22.
When an abnormal gamete carrying two copies of chromosome 22 merges with a normal gamete, the resulting zygote has three copies. This extra genetic material is copied into every cell of the developing embryo through subsequent cell divisions, leading to the full trisomy condition. This random meiotic error is responsible for the majority of Trisomy 22 cases.
Types of Trisomy 22
Trisomy 22 can manifest in different forms depending on when the cell division error occurs, leading to variations in severity and outcome. The most common and severe form is Full Trisomy 22, where every cell in the body contains three complete copies of chromosome 22. This global genetic imbalance frequently results in miscarriage during early pregnancy, as the developing fetus cannot survive the disruption to organ formation.
A less severe variation is Mosaic Trisomy 22, where the extra chromosome 22 is present in only some of the body’s cells. This condition arises from a nondisjunction error that occurs after fertilization, during the early mitotic cell divisions of the embryo. The severity of mosaicism is highly variable and depends on the proportion and location of the cells that contain the extra chromosome.
A third form is Translocation Trisomy 22, which involves a rearrangement of genetic material. This happens when a piece of chromosome 22, or the entire extra chromosome, is attached to another non-homologous chromosome, such as chromosome 11. Although the overall number of chromosomes may still be 46, the individual has the genetic equivalent of three copies of chromosome 22 material, leading to the condition.
Factors Increasing Likelihood
The occurrence of Trisomy 22 is primarily a sporadic, random event, but certain biological factors increase the likelihood of nondisjunction. The most well-established factor is advanced maternal age. As a woman ages, the eggs stored in her ovaries also age, and the mechanisms that ensure correct chromosome separation during meiosis become less reliable.
The risk for any chromosomal abnormality increases starting around age 35, a general trend that applies to Trisomy 22. This correlation is due to the greater chance of meiotic errors, rather than environmental or lifestyle factors. Although advanced paternal age is less strongly linked to Trisomy 22 compared to other trisomies, the overall quality of gamete production is a factor in all chromosomal conditions.
Recurrence Risk and Genetic Counseling
For most families who have experienced a pregnancy affected by Full or Mosaic Trisomy 22, the recurrence risk in a future pregnancy is considered low, similar to the risk associated with the mother’s age. This is because the underlying cause is a random error in egg or sperm production, which is unlikely to repeat. These cases are viewed as isolated, chance events.
The exception to this low recurrence risk is Translocation Trisomy 22. In this scenario, one parent may be a “balanced carrier,” meaning they have the rearranged chromosome 22 material but do not exhibit symptoms. A balanced carrier has a significantly higher risk of producing gametes with an unbalanced (trisomic) set of chromosomes.
Following a diagnosis, genetic counseling is recommended to clarify the specific type of Trisomy 22 and determine the recurrence risk. The counselor often recommends karyotyping, a test that maps the parents’ chromosomes, to check for a balanced translocation. This information is important for family planning and deciding on prenatal diagnostic testing options for future pregnancies.