Definition:

Down syndrome (DS), a genetic condition characterized by mental retardation and distinctive facial appearance, is caused by trisomy of chromosome 21 (HSA21). Down syndrome (DS) is the most common chromosomal malformation in newborns. Throughout the world, the overall prevalence of DS is 1 per 1,000 live births, although in recent years this figure has been increasing. Roughly 95% of cases of DS are due to the presence of an extra (third) copy of HSA21. Most often, the non-disjunction event leading to DS occurs in maternal meiosis I. In about 5% of patients, 1 copy is translocated to another acrocentric chromosome, most often chromosome 14 or 21. In 2 to 4% of cases with free trisomy 21 there is recognizable mosaicism for a trisomic and a normal cell line. DS occurs at a much higher incidence in older mothers. Nonetheless, the vast majority of DS births are to younger mothers. Clinical and experimental studies have shown that age independent DNA hypo-methylation is associated with chromosomal instability and abnormal segregation. Recent studies have linked the increased frequency of polymorphism of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase gene (MTRR) in mothers with DS child. The phenotypic features of DS are quite variable from person to person and include learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. This phenotypic variation is likely to be caused by a combination of environmental and genetic causes. Genetic polymorphisms in both Hsa21 and non-Hsa21 genes may account for much of this variation. Trisomy of Hsa21 has a significant impact on the development of many tissues, most notably the heart and the brain. A recent paper has suggested that RCAN1 and DYRK1A, localized in the Down syndrome critical region (DSCR) of HSA21, may have an impact on the development of multiple tissues.