Trisomy 22 is a chromosomal disorder characterized by the presence of an extra copy of chromosome 22, meaning individuals have three copies instead of the usual two in some or all of their cells. This genetic alteration can lead to a range of developmental and health challenges. Understanding its origins involves examining the fundamental processes of human genetics.
Understanding Chromosomes and Cell Division
Human cells contain 46 chromosomes, organized into 23 pairs. These chromosomes are structures within cells that carry our genetic material (DNA), which contains the instructions for building and operating the body. One set of 23 chromosomes comes from the mother and the other set from the father.
Cell division is a fundamental process that ensures growth and repair. Meiosis is a specialized type of cell division that occurs in the formation of egg and sperm cells. This process reduces the chromosome number by half, ensuring the resulting embryo has 46 chromosomes after fertilization. Mitosis is cell division for growth and repair in other body cells, producing two genetically identical daughter cells.
Primary Genetic Mechanisms Leading to Trisomy 22
The most common genetic cause of Trisomy 22 is an error during cell division called nondisjunction. Nondisjunction occurs when chromosomes fail to separate properly during meiosis (in egg or sperm formation) or early mitotic divisions after fertilization. If this happens during meiosis, a gamete may end up with an extra chromosome 22.
When such an abnormal gamete combines with a normal gamete during fertilization, the resulting embryo will have three copies of chromosome 22 in every cell. This error arises spontaneously and is not inherited from the parents. Another mechanism leading to Trisomy 22 is translocation, where a segment of chromosome 22 breaks off and attaches to another chromosome.
Unbalanced translocations lead to Trisomy 22 when there is extra genetic material from chromosome 22. These can occur spontaneously or be inherited from a parent who carries a balanced translocation. A parent with a balanced translocation has no health issues as they have the correct amount of genetic material, only rearranged.
Different Forms of Trisomy 22
Trisomy 22 can manifest in several forms, depending on which cells are affected and the extent of the chromosomal alteration. Full Trisomy 22 occurs when every cell in the body has an extra copy of chromosome 22. This form results from nondisjunction during gamete formation and is associated with severe health outcomes, often leading to miscarriage.
Mosaic Trisomy 22 is characterized by the presence of an extra chromosome 22 in only some of the body’s cells, while other cells have the normal two copies. This mosaic pattern arises from an error during early mitotic cell division after fertilization, indicating the original fertilized egg had a normal chromosome count. The severity of mosaic Trisomy 22 can vary widely depending on the proportion and distribution of affected cells.
Partial Trisomy 22 involves the duplication of only a segment of chromosome 22, rather than the entire chromosome. This form results from an unbalanced translocation, where a piece of chromosome 22 is abnormally attached to another chromosome. The specific health effects in partial Trisomy 22 depend on which genes or regions of chromosome 22 are duplicated.
Factors Influencing Occurrence
Advanced maternal age is a factor influencing the risk of chromosomal abnormalities, including Trisomy 22. As women age, the likelihood of nondisjunction errors occurring in their egg cells increases. This heightened risk is due to the longer duration egg cells are stored, which can lead to issues during the complex process of meiosis.
Most cases of Trisomy 22, particularly full trisomy due to nondisjunction, are considered de novo events, occurring spontaneously and not inherited from either parent. Inherited cases are rare and involve a parent carrying a balanced chromosomal translocation. While the parent with a balanced translocation is healthy, they can pass on an unbalanced form to their child, leading to partial Trisomy 22.