An update on the genetics of Down Syndrome

First described in 1866 by Sir John Langdon Down, Down syndrome is a common genetic condition with an incidence of approximately 1 in 800 live births. It was not until 1959 however, that Lejeune determined the presence of an extra copy of chromosome 21 as the genetic basis of the syndrome. In 95% of the cases of Down syndrome it is due to a chance or sporadic event and not inherited as the term is often used. Most cases of Down syndrome are due to non-disjunction, a process in which there is a faulty separation of the chromosomes during egg and sperm formation.

There are characteristic physical features of Down syndrome including short stature, poor muscle tone, specific facial appearance, and delays in reaching developmental milestones. Many individuals with Down syndrome have health concerns including heart abnormalities, digestive system blockages, and increased susceptibility to respiratory infections. Associated with Down syndrome is a slightly increased risk for developing childhood leukemia and an increased risk of Alzheimer disease at an earlier age than the general population. The degree of mental retardation in these patients can range from mild to moderate but children can maximize their potential if provided a stimulating learning environment.

One of the research questions regarding Down syndrome is the actual cause for the mental retardation. Last month researchers at the Stanford University School of Medicine and Lucile Packard Children’s Hospital’s Down Syndrome Center, published results indicating that a specific gene, when overactive, affects certain nerve cells or neurons in the brain causing them to degenerate and stop normal functioning. The gene, known as App, is on chromosome 21 and can cause early-onset Alzheimer disease but this research was the first to link this gene to specific brain neurons in Down syndrome patients. The Stanford researchers suggest that the mental retardation of Down syndrome is the result of an overactive gene that interrupts normal communication between neurons in a specific region of the brain.

As with many early research results there is the hope for soon to follow treatment. It is important to note that there is significant work remaining: 1) Is there more than one gene is involved? If so, how do they interact? 2) Determine how App works in the nervous system cells 3) What compounds might be effective in decreasing the effect of the over active protein of the gene?

It is an exciting discovery. If and when researchers can achieve the above tasks, there may be concrete ways to help individuals with Down syndrome develop more normally.