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Why does the chance of Down syndrome increase with maternal age?

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BRCA2 tumor suppressor gene on chromosome 13 — human genetic disease Photomicrograph of the *BRCA2* tumor suppressor gene on chromosome 13 of the human genome. Inactivation of this growth-regulating gene is associated with a higher risk of developing breast cancer.

The increased risk of Down syndrome in the offspring of older women is primarily linked to meiotic nondisjunction, which is the unequal division of chromosomes during the formation of egg cells.1

While the precise biochemical mechanisms behind this process remain unknown, the risk of such numerical chromosomal abnormalities rises in an almost exponential manner as maternal age increases, particularly after age 35. This phenomenon is associated with the natural aging process of the ovaries and a decline in the quality of eggs. Because these chromosomal errors occur as independent meiotic events, the risk is specific to the age of the mother at the time of conception rather than a cumulative genetic trait, and there is no comparable effect observed regarding paternal age.12