Down syndrome is a genetic condition occurring when an individual has an extra full or partial copy of chromosome 21. This extra genetic material influences characteristic physical features and developmental differences. Most cases are not inherited from parents, but a rare exception allows it to be passed down through families.
The Genetic Foundation of Down Syndrome
Human cells typically contain 23 pairs of chromosomes, totaling 46, with one chromosome from each pair inherited from each parent. Down syndrome arises from an unusual cell division involving chromosome 21, resulting in an extra full or partial copy of this chromosome.
The most common type, Trisomy 21, accounts for about 95% of Down syndrome cases. In Trisomy 21, every cell has three copies of chromosome 21 instead of the usual two. This occurs due to a random error in cell division, called nondisjunction, during the formation of reproductive cells or early embryonic development. This random event is not inherited.
Another rarer type is Mosaic Down syndrome, affecting about 1-2% of individuals. In Mosaic Down syndrome, only some cells have an extra copy of chromosome 21, while others have the typical two copies. This mosaic pattern arises from an unusual cell division error that happens after fertilization, early in development. This type is also not inherited.
When Down Syndrome Can Be Inherited
Translocation Down syndrome is the third type, present in about 3-4% of cases. In this form, an extra part or a whole extra chromosome 21 becomes attached, or translocated, to another chromosome, rather than existing as a separate chromosome. While some translocation cases occur randomly, approximately one-third of these (about 1% of all Down syndrome cases) are inherited from a parent.
Inheritance happens when a parent carries a “balanced translocation.” A parent with a balanced translocation has the correct amount of genetic material, but it is rearranged, meaning a piece of chromosome 21 is attached to another chromosome. Because there is no net gain or loss of genetic material, these parents typically do not show symptoms of Down syndrome themselves. However, during the formation of reproductive cells, this balanced translocation can become unbalanced.
If a parent with a balanced translocation passes on an unbalanced set of chromosomes to their child, the child will receive extra genetic material from chromosome 21, resulting in Translocation Down syndrome. The recurrence risk for parents who are carriers varies. If the mother is the carrier of a common translocation involving chromosome 21 and another chromosome (e.g., 14), the chance of having another child with Down syndrome can be about 10-15%. If the father is the carrier, the risk is typically lower, around 2.5-5%. In rare instances where a parent carries a translocation involving two chromosome 21s, the risk of having a child with Down syndrome is 100%.
Genetic Counseling and Family Planning
Genetic counseling plays an important role for families seeking to understand the risks associated with Down syndrome. A genetic counselor can assess individual circumstances, interpret genetic test results, and provide comprehensive information and support. This process helps families understand the specific genetic cause of Down syndrome in their child and determine recurrence risks for future pregnancies.
Genetic counseling is often recommended if a child is diagnosed with Translocation Down syndrome. It is also advised if there is a family history of translocation or in cases of advanced maternal age, as older eggs carry a higher risk of unusual chromosome division. During counseling, options such as prenatal diagnostic tests, including amniocentesis or chorionic villus sampling (CVS), may be discussed to analyze the baby’s chromosomes. Carrier testing for parents can also determine if either parent carries a balanced translocation, enabling informed family planning decisions.