What is Trisomy 21 (Down syndrome)?
Trisomy 21 is a neurodevelopmental and neurodegenerative genetic disorder caused by an error in division of the sex cells (the sperm or egg) prior to fertilization. This error is technically called a “nondisjunction” and results in one of the parents contributing two copies of chromosome 21 to the newly formed embryo rather than one. Once fertilization has taken place the young unborn child has an extra 21st chromosome, or a “trisomy”. In most cases this extra chromosome comes from the mother but it can also come from the father.
How many chromosomes do we have?
Humans have 23 pair of chromosomes, or a total of 46. A person affected by trisomy 21 has an extra 21st chromosome, or a total of 47. In most individuals this trisomy is present in every cell of the body, however there are some kinds of trisomy 21 where not every cell is affected. This is called “mosaicism“. Mosaic Down syndrome is very rare and occurs in perhaps only 2% to 4% of the incidences of Down syndrome.
What is a chromosome?
A chromosome is a single piece of DNA. When chromosomes are chained together into a full set of 46, they form the DNA helix. This is where our entire genetic code is written. If a nondisjunction occurs and fertilization takes place, a trisomy occurs and the newly created person has an extra chromosome. The most common trisomy is trisomy 21 which is commonly called Down syndrome, but trisomies can also occur on chromosome 18 (Edwards syndrome), chromosome 13 (Patau syndrome), and others. Trisomy 21 occurs in approximately 1 in 700 live births.
What does one additional chromosome do?
Some trisomies are not compatible with life and result in miscarriage. Trisomy 21 and 18 are the most common in live births, but individuals who are born with trisomy 21 have the greatest chance of surviving well into adulthood. In fact, the average life expectancy for an individual with Down syndrome at present is about 55 years. There are, of course, physical and intellectual difficulties associated with Down syndrome. The 21st chromosome is one of the smaller of our chromosomes, but researchers estimate that there are between 300 and 400 genes that reside there. The extra copy of chromosome 21 results in a superabundance of the proteins regulated on those genes and that superabundance causes the well-known physical characteristics that we recognize as Down syndrome, the health issues, and also the intellectual disability.
In the words of Jérôme Lejeune:
“Their eyes are slightly oblique, their nose very small in their round face and features incompletely chiseled. Every child has short hands and short fingers. Theirs are shorter. Their entire anatomy is like rounded, without harshness or stiffness. Their ligaments, their muscles have a flexibility that gives a tender listlessness to their way of being. And this sweetness extends to their character, expansive and affectionate. Children with Down Syndrome are more ‘childish’ than others. They have a special charm, easier to cherish than to describe.”
Can you cure trisomy 21?
Jerome Lejeune spoke of a “cure” but researchers today believe the word “treatment” is more appropriate. Most likely treatments in the first few years will be like treatments for diabetes, or other conditions that are managed by a daily regimen of drug therapy. The immediate aim of researchers is to curb the over-expression of the extra chromosome by searching for inhibitory or blocking molecules. However, in these days of rapidly developing science we would be foolish to say that a cure will never be possible. A cure was Jerome Lejeune’s goal, because he realized that unless a cure could be found, individuals conceived with Down syndrome would become a target of a eugenics movement that sought to “cure” Down syndrome through prenatal diagnosis and abortion.
How are treatments possible?
Researchers have now identified certain genes on chromosome 21 that they believe are responsible for mental deficiency. Each of these genes “encodes”, or produces, one or several proteins, or enzymes, which are integral to physical and intellectual functioning. While it is very difficult to act the genes themselves, scientists have discovered that they can have a regulatory effect upon the proteins encoded by these genes.
For example, one gene on the 21st chromosome is called cystathionine beta synthase, or CBS for short. Over-expression of this gene is known to be one of the causes of the intellectual disability associated with Down syndrome. The Jerome Lejeune Foundation has obtained a patent on a family of molecules that has shown to be effective in regulating the production of enzymes produced by CBS. If these molecules stand up to further testing and rigorous clinical trials, then they will likely be manufactured into drugs that individuals can take each day, and that may improve their intellectual capacity, perhaps even by as much as 20 to 25%!
Then there is hope?
Yes! There is tremendous hope, and teams of researchers around the world, many who are funded by the Jerome Lejeune Foundation, are working vigorously to make hope a reality as soon as possible.
Will the research take a long time?
The first clinical trials have begun, but there is much to do. Optimistic researchers believe they will have treatments commercially available to treat the intellectual disability associated with Down syndrome within 10 years. Of course, research is expensive. Researchers can only work when funding is available, and funding for Down syndrome is scarce. The Jerome Lejeune Foundation is the worlds oldest and largest funder of research on Down syndrome. Your support can make an incredible difference in hastening the race to find treatments for Down syndrome and other genetic intellectual disabilities.