How does Down syndrome result from an extra copy of chromosome 21?

Down syndrome, also known as trisomy 21, occurs when an individual has an extra copy of chromosome 21, resulting in three copies instead of the typical two. This condition arises from numerical chromosomal abnormalities, which are generally caused by meiotic nondisjunction—a random, unequal division of chromosomes during the formation of egg or sperm cells.123

When this error occurs, the resulting gamete carries an additional chromosome 21. Upon fertilization, the embryo inherits this extra genetic material, leading to the presence of three copies of the chromosome in some or all of the body's cells. The presence of this extra genetic material disrupts normal development, giving rise to the physical and cognitive characteristics associated with the disorder.12

While the most common form involves an entire extra chromosome in all cells, other types include mosaic Down syndrome, where only some cells are affected, and translocation Down syndrome, where an extra piece of chromosome 21 attaches to another chromosome. The risk of conceiving a child with trisomy 21 increases significantly with maternal age.23