Down Syndrome: Genetic Cause

Down Syndrome: Genetic Cause

Down syndrome, also known as trisomy 21, is a genetic disorder that affects approximately 1 in every 1,000 live births in the United States and Europe. It is caused by the presence of an extra partial or complete chromosome 21 in every cell, resulting in 47 chromosomes instead of the usual 46.

The extra chromosome 21 is the direct cause of Down syndrome, but the indirect causes responsible for the extra chromosome are still being researched. Down syndrome is not caused by anything the mother does or does not do during pregnancy.

There are three types of Down syndrome:

1. Meiotic nondisjunction: An error occurs in the separation of the pair of 21 chromosomes during cell division in the process of formation of sperm or egg, resulting in a child with 47 chromosomes in every cell. This accounts for approximately 95% of Down syndrome occurrences.
2. Translocation: In approximately three percent of individuals with Down syndrome, the extra copy of chromosome 21 is attached to another chromosome, rather than in the usual position on chromosome 21.

While Down syndrome is primarily caused by an extra copy of chromosome 21, recent research has suggested that other genes in the PI3K-AKT-mTOR signalling pathway may have important roles in patients with macrocephaly and developmental delay or autism spectrum disorder. The study identified ten pathogenic/likely pathogenic mutations in PTEN, PIK3CA, MTOR, and PPP2R5D in ten patients with macrocephaly and developmental delay/autism spectrum disorder. These mutations were found to have a lower developmental quotient than the rest of the cohort.

While Down syndrome is not caused by a mutation in the PI3K-AKT-mTOR pathway, the study highlights the complex genetic landscape of developmental disorders and the importance of considering multiple genes in understanding the condition.