How do the genes on chromosome 21 cause Down's syndrome?

I have a new grandson, born just after Thanksgiving, who has Down Syndrome. He’s having open-heart surgery tomorrow to correct a defect that would kill him otherwise.

I’ve looked up everything I can about the condition, and one of the questions that remains in my mind is exactly how the specific genes on chromosome 21 cause the various symptoms. For example, this site lists the specific genes and what each one does, but I can’t see why any of these would cause things like a heart defect, or a characteristic eye shape, or any of the other typical symptoms.

I’m hoping that among the teeming millions there is someone who knows, or who can point me toward, an explanation.

As far as I understand (biology grad student, fairly good background in genetics/molecular biology), it has to do with the overexpression of the genes in Chromosome 21. For most genes, barring those on the sex chromosomes, you have two copies. However, a person with Down syndrome has three copies of all or some of the genes on 21, leading higher levels of expression than normal.

The genes themselves are probably widely involved in various developmental and growth processes, and it just happens to be the case that overexpression leads to very characteristic symptoms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180222/ This is a fairly comprehensive review article discussing the research that has gone into identifying the specific genes involved. It may be a bit technical, but I think it might be helpful to you. If you want to ask me any questions about terminology or whatnot, I’ll try my best to answer.

Thank you very much! That is just what I was looking for.

The term to search on is “dosage”.

Anther article that may be a bit difficult to wade through is Gene-dosage effects in Down syndrome and trisomic mouse models which established that many of the physical aspects of Down Syndrome are related to dosage effects.

If you have any particular questions send a PM. I can drag my genetics degree off the shelf and try to help a bot.