Causes of Down Syndrome
The development of an embryo begins with a natural egg cell and a sperm cell, each containing 46 chromosomes. These cells subsequently divide, resulting in each gamete carrying 23 chromosomes. These chromosomes hold the genetic material known as deoxyribonucleic acid (DNA), which is present in all human cells and plays a crucial role in determining various traits of the child, such as height, hair texture, and skin color. These chromosomes are inherited from the parents, with fertilization of a sperm cell (containing 23 chromosomes) by an egg cell (also containing 23 chromosomes) producing an embryo with a complete set of 46 chromosomes—half from the father and half from the mother.
In the case of Down syndrome, a child is born with an extra copy of chromosome 21, leading to distinct physical characteristics and developmental challenges associated with the condition. While researchers understand that the syndrome is caused by the presence of an additional chromosome, the exact reason for this occurrence remains uncertain, and the myriad factors contributing to it are not fully understood. There are, in fact, three types of Down syndrome, which are typically differentiated through chromosomal testing due to the similarities in physical and behavioral characteristics.
Trisomy 21
Trisomy 21 is the most prevalent form of Down syndrome, accounting for approximately 95% of cases. In this type, an abnormal cell division results in an extra copy of chromosome 21 present in every cell. This occurs when the chromosome pairs fail to separate properly during fertilization or prior to it, either in the egg or sperm. To clarify, errors can sometimes arise during the division of the 46 chromosomes, causing the formation of an egg or sperm that carries two copies of chromosome 21 instead of one. If this egg or sperm is involved in fertilization, the resulting embryo will have three copies of chromosome 21, a condition referred to as Trisomy 21. As the embryo develops, the extra chromosome replicates in all body cells, leading to an overproduction of biochemical substances that are regulated by the genes located on chromosome 21. Researchers are still uncertain about why there is an additional copy of chromosome 21 in these cases.
It is noted that the majority of Trisomy 21 cases derive the extra chromosome from the mother (over 90%), while fewer than 10% inherit it from the father. This information has been obtained through family linkage studies, primarily involving parents and their children with Down syndrome, aimed at tracing DNA markers along chromosome 21.
Translocation Down Syndrome
Translocation Down syndrome affects a small percentage, approximately 3%, of individuals with the syndrome. This variant occurs when a portion of chromosome 21 attaches to another chromosome during the production of gametes (the egg and sperm), either in the early stages of embryonic development or in the parents. Sometimes, a segment of chromosome 21 may link with another chromosome, typically chromosome 13, 14, or 15, at or near the time of fertilization, resulting in three copies of chromosome 21—two normal copies and one that carries additional genes from the fused chromosome.
Parents can carry a rearranged genetic material between chromosome 21 and another chromosome without any gain or loss of genetic material, known as a balanced translocation. Generally, individuals with balanced translocations experience no health issues, but passing this rearrangement to their offspring can lead to an unbalanced translocation where chromosome 21 is involved, thus potentially causing Down syndrome. Importantly, this type of Down syndrome can be inherited from parents who do not display symptoms of the syndrome.
In these cases, some parents may seem perfectly healthy and exhibit no characteristics of Down syndrome, possessing a normal copy of chromosome 21 along with another version that contains a missing segment and a normal copy of chromosome 14 alongside another that carries an extra segment of chromosome 21. This additional segment can be passed down to their children, resulting in Down syndrome.
Mosaic Down Syndrome
Mosaic Down syndrome represents a rare form of the condition, affecting approximately 2% of individuals diagnosed. The term “mosaic” refers to the mixture of cells; some cells in the body contain the standard two copies of chromosome 21 while other cells possess three copies. This mosaic pattern can manifest within different tissue types, resulting in a combination of normal and affected cells. This variation occurs due to a random event during cell division in the early stages of embryonic development, meaning the error happens after fertilization.
It is essential to understand that individuals with mosaic Down syndrome often exhibit fewer symptoms and characteristics compared to those with other forms of the syndrome. Some individuals may not display several signs associated with Down syndrome, as the number of cells carrying the additional chromosome is relatively low. The severity of the condition in each affected person depends on the number of cells in their body that are impacted by Down syndrome.
Genetic Factors in Down Syndrome
As previously mentioned, Down syndrome arises from an error in cell division during the early developmental stages of the embryo. In most instances, it is classified as a non-inherited condition. However, Down syndrome resulting from translocation can be passed from parents to children. The likelihood of this translocation transfer depends on the sex of the parent carrying the rearranged chromosome 21, with the risk of transmission being higher if the mother carries the altered chromosome. Moreover, the risk of having future pregnancies with Down syndrome increases when one child has already been born with the condition due to a translocational rearrangement, as one of the parents is a carrier of a balanced chromosomal translocation. It is advisable for parents to consult a genetic counselor to assess their specific risks when considering future pregnancies, particularly in cases involving translocated chromosome 21. It is crucial to note that there are no environmental or behavioral causes linked to Down syndrome.
Risk Factors for Down Syndrome
There is no evidence to suggest that parental activities, either during or prior to pregnancy, contribute to the risk of any type of Down syndrome. It is essential to understand that nothing a mother does during pregnancy causes Down syndrome. However, the following factors may increase the likelihood of Down syndrome:
- Maternal Age: The likelihood of having a child with Down syndrome increases significantly for mothers who are 35 years or older compared to younger women. Nevertheless, the majority of children with Down syndrome are born to mothers younger than 35, attributed to higher birth rates among this age group. Additionally, the chances of conceiving a baby with Down syndrome increase when mothers become pregnant in their teenage years.
- Genetic Translocation: Parents can pass a genetic translocation related to Down syndrome to their offspring.
- Previous Child with Down Syndrome: If parents have had one child with Down syndrome, the likelihood of having another child with the condition is raised.
- Sibling with Down Syndrome: If a sibling has Down syndrome, it may increase the risk for other children in the family.
Preventing Down Syndrome
Although there is no definitive way to prevent Down syndrome, the risk of its occurrence decreases in cases where children are conceived at a younger age. It is recommended that couples at a higher risk, or those who have previously had a child with Down syndrome, consult a genetic counselor before conception. A genetic counselor is trained to assist individuals in understanding genetic conditions, congenital anomalies, and how these aspects may impact maternal and fetal health. They can help estimate the likelihood of having a child with Down syndrome and discuss risks in future pregnancies, as well as available prenatal testing options for chromosomal abnormalities in the fetus. This includes clarifying the benefits and drawbacks of such tests. Some health organizations recommend that all pregnant women, regardless of age, undergo screening for Down syndrome, but it is prudent to discuss this screening with a healthcare provider.