What are the mechanisms of down syndrome?

Extra chromosome 21: At it's core, having an extra copy of chromosome 21 leads to more of everything encoded by 21 -- genes, non-coding elements like micrornas, etc. This in turn leads to changes in the program of how a person is built, and results in the many physical issues faced by patients with trisomy 21. Recent review: http://www.Ncbi.Nlm.Nih.Gov/pmc/articles/pmc3180222/.

Several possible: The features of Down syndrome seem to be dependent on the addition of one extra segment of a 21 chromosome.You can get there several ways. The traditional ds (~95%) has 3 copies of a 21 chromosome. About 4% have the specific extra 21 piece stuck on a regular chromosome.About 1% have a mosaic of some normal and some 21 trisomy in variable amounts.

Gene triplication: Down syndrome involves genes of chromosome 21 having too many copies. Most common is trisomy or three copies of the genes. Another form is translocation where extra copies break off and lodge elsewhere. This happens usually as just an error during development of the fetus. Occasional cases can be genetically transmitted. Why these extra copies cause effects on organs is not understood.

Extra genes, HSA21q: An extra copy of the long arm of chromosome 21 increases expression of > 500 genes in that area, which have many different functions. Brain size is reduced; areas with fewer neurons "match" the neurodevelopmental profile (e.g., intellectual disability, poor memory). Dendrites start losing branches at 6 mos. & are abnormal by age 2; hence, low ability in language, visual-spatial abilities & more.