Down Syndrome (Trisomy-21) (2n = 47, +21)

    Down Syndrome (Trisomy-21) occurs as a results of non-disjunction of chromosomes during meiosis, such that the gamete contributed by one (unaffected) parent has two copies of Chromosome 21. When fertilized by a gamete from the other parent, with a single Chromosome 21, the result is a trisomy (three copies: see G-banding karyotype). Trisomy 21 is the most common trisomy, and occurs in about 1 / 1,000 live births. The incidence is up to 50-fold higher in older mothers. The syndrome is characterized by a distinctive facial phenotype including epicanthic eye folds, a broad flat face, characteristic palm crease, and moderate to severe mental retardation, as well as other medical conditions noted above. The stereotypical phenotype of persons with Down Syndrome is often a white male with dark hair (see second photo), however Trisomy 21 occurs in both sexes and in all ethnicities. Many persons with Down Syndrome function well in the community. See the website of the Down Syndrome Research Foundation [] for more information.

   Most or all persons with Down Syndrome are functionally sterile, and do not pass on gametes with the duplicated chromosome to the next generation. Thus, although the condition is "genetic," it is not "inherited" in the same sense as are  single-locus traits, and its occurrence in the population is termed "sporadic". In very rare cases, Down Syndrome may result from a balanced translocation that attaches a substantial portion of Chromosome 21 to another chromosome (usually Chromosome 14) [this is indicated as 2n=46,t(q14q21)]. This form of Down Syndrome may be passed genetically (by asymptomatic, non-Down Syndrome parents) to the next generation. For this reason, it is considered advisable to check the karyotype of all persons with Down Syndrome, to provide appropriate genetic counseling.

    Recent research suggests that the characteristic features of the Down Syndrome phenotype are due to the triplication of a small set of genes on Chromosome 21, rather than the trisomy per se. Selective re-regulation of the expression of one or a few key "Down Syndrome Critical Region"(DSCR)  gene loci in utero might therefore provide an effective means of treatment.  Study of the homologous genes in Drosophila may provide means to this end. A former US politician's trivialization of government-funded Drosophila research as irrelevant to human concerns is thus misinformed.

    Prenatal diagnosis of Down Syndrome typically amniocentesis to recover fetal cells from the maternal amniotic fluid, which can then be cultured to check their karyotype. Test results may not be possible until late in pregnancy. Several new DNA-based tests have been developed that take advantage of Next-Generation sequencing methods to diagnose Down Syndrome pregnancies much earlier in development.

        Sheilgah O'Leary

Carole, age 40; Children with Trisomy 21 competing at the Special Olympics; Catherine;
Abigail, from the exhibition "More Than Meets the Eye," St John's Arts & Culture Centre

Figures ©2002 by Griffiths et al. & ©2011 by Russell; ©2009 by Sheilagh O'Leary; all text material ©2014 by Steven M. Carr