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Down syndrome (also Down's syndrome) encompasses a number of genetic disorders, of which trisomy 21 is the most representative, causing mental retardation. Incidence of Down syndrome is estimated at 1 per 660 births and is the most common chromosomal abnormality. It is a commonly known observation that maternal age influences the risk of conceiving a baby with the syndrome. At age 20-24, it is only 1/1490, while at age 40 it is 1/11. (Hook EB. Rates of chromosomal abnormalities at different maternal ages. Obstet Gynecol 1981;58:282.)
Down syndrome is named after John Langdon Haydon Down, who first described the condition. It was originally called mongolism, after a perceived resemblance observed by Down between the faces of some of his patients with Down syndrome and the mongoloid race. This usage, like other medical terms used at the time, has become a term of abuse, and is now generally viewed as both offensive and medically meaningless.
Trisomy 21 is the existence of the third copy of the chromosome 21 in cells throughout the body of the affected person. Whatever the actual molecular reason, this condition puts children with Down syndrome at immediate disadvantage as compared with non-Down children. The IQ of a child with Down syndrome is rarely measured above 60. The brain of children with Down syndrome is usually small and underweight. The cerebellum and brain stem are unusually small. So is the superior temporal gyrus. Intellectual potential is further limited by a number of ailments such as recurring infectious diseases, heart problems, poor eyesight, etc.
However, medical treatment, a conducive family environment, vocational training, etc. can produce excellent progress in the overall development of children with Down syndrome. On the one hand, Down syndrome shows that we cannot jump over genetic limitations; on the other, it shows that intense training can produce miracles whatever the starting point. The commitment of parents, therapists, and doctors to individual children has produced previously unexpected positive results.
Of the inborn disorders that affect intellectual capacity, Down syndrome is the most prevalent and best studied. Down syndrome is a term used to encompass a number of genetic disorders of which trisomy 21 is the most representative (95% of cases). Trisomy 21 is the existence of the third copy of the chromosome 21 in cells throughout the body of the affected person. Other Down syndrome disorders are based on the duplication of the same subset of genes (e.g., various translocations of chromosome 21). Depending on the actual etiology, the learning disability may range from mild to severe.
Trisomy 21 results in over-expression of genes located on chromosome 21. One of these is the superoxide dismutase gene. Some (but not all) studies have shown that the activity of the superoxide dismutase enzyme (SOD) is elevated in Down syndrome. SOD converts oxygen radicals to hydrogen peroxide and water. Oxygen radicals produced in cells can be damaging to cellular structures, hence the important role of SOD. However, the hypothesis says that once SOD activity increases disproportionately to enzymes responsible for removal of hydrogen peroxide (e.g., glutathione peroxidase), the cells will suffer from a peroxide damage. Some scientists believe that the treatment of Down syndrome neurons with free radical scavengers can substantially prevent neuronal degeneration. Oxidative damage to neurons results in rapid brain aging similar to that of Alzheimer's disease.
Another chromosome 21 gene that might predispose Down syndrome individuals to develop Alzheimer's pathology is the gene that encodes the precursor of the amyloid protein. Neurofibrillary tangles and amyloid plaques are commonly found in both Down syndrome and Alzheimer's individuals. Layer II of the entorhinal cortex and the subiculum, both critical for memory consolidation, are one of the first affected by the damage. A gradual decrease in the number of nerve cells throughout the cortex follows. A few years ago, Johns Hopkins scientists created a genetically engineered mouse called Ts65Dn (segmental trisomy 16 mouse) as an excellent model for studying the Down syndrome. Ts65Dn mouse has genes on chromosomes 16 that are very similar to the human chromosome 21 genes. With this animal model, the exact causes of Down syndrome neurological symptoms may soon be elucidated. Naturally, Ts65Dn research is also likely to highly benefit Alzheimer's research.