From the Guidelines
Down syndrome is primarily caused by the presence of an extra copy of Chromosome 21, resulting from sporadic nondisjunction during parental meiosis, with approximately 95% of cases being maternal in origin 1. The etiology of Down syndrome is complex, involving various genetic mechanisms. The most common cause is nondisjunction, where chromosome pairs fail to separate properly during cell division, resulting in an extra copy of Chromosome 21. This occurs randomly during the formation of reproductive cells or during early fetal development. Some key points to consider include:
- Advanced maternal age significantly increases the risk of having a child with Down syndrome, with women over 35 having a higher chance 1.
- The risk of having a child with Down syndrome can be inherited when one parent carries a translocation involving chromosome 21, such as a Robertsonian translocation 1.
- Less commonly, Down syndrome can result from translocation or mosaicism, where only some cells have the extra chromosome. The condition is not caused by anything parents do before or during pregnancy, and it cannot be prevented. Prenatal screening and diagnostic tests, such as those described in the technical standards and guidelines for prenatal screening for Down syndrome 1, can detect Down syndrome during pregnancy, allowing families to prepare for the birth of a child with special needs.
From the Research
Causes of Down Syndrome
- Nondisjunction of chromosome 21 is the leading cause of Down syndrome, with two risk factors being increased maternal age and altered recombination 2.
- Maternal meiosis I and II errors are the most common causes of nondisjunction, with maternal meiosis I errors being more frequent 2, 3.
- A single exchange within the pericentromeric region of 21q can interact with maternal age-related risk factors, increasing the susceptibility to nondisjunction 2.
- Telomeric exchanges can also impose a risk for nondisjunction, irrespective of the age of the oocyte 2.
- Mosaicism for trisomy 21 can occur, where an individual has a mixture of cells with 46 and 47 chromosomes, and this can be a cause of Down syndrome 4, 5.
- Environmental factors, such as intensive drug therapy during the periconceptual period, may also be associated with maternal meiotic non-disjunction of chromosome 21 3.
- Further chromosome mis-segregation and mosaic aneuploidy can also contribute to the phenotypic variability observed in people with Down syndrome 6.
Risk Factors
- Increased maternal age is a well-established risk factor for nondisjunction of chromosome 21 2, 3.
- Altered recombination is also a risk factor for nondisjunction of chromosome 21 2.
- Exposure to irradiation, alcohol, tobacco, and mutagenic substances may also be associated with an increased risk of nondisjunction, although the evidence is not conclusive 3.
- Sociogenetic factors, such as parental age and environmental effects, can also play a role in the risk of nondisjunction 3.