Professor Ostrowski, Professor McNally
Down Syndrome is a chromosomal abnormality that results in an easily recognizable phenotype.
This abnormality occurs in about 1 in every 800 to 1000 male and female births. The common features are
low ears, epicanthal folds, enlarged tongues, and microcephaly. Down Syndrome children are affected by
mental retardation and retarded physical skills. People with this abnormality used to be considered
hopeless. However, due to advancements in medicine and science, they are far from hopeless, and can lead
normal lives. The good news is that Down Syndrome people can live to be as old as 80 and lead normal
lives and participate in specialized physical activities and even be TV or movie stars.
Down Syndrome had been observed and documented for centuries. However, it was not until the
late nineteenth century that John Langdon Down, an English physician, published an accurate description
of a person with Down Syndrome.1 Henceforth, Down was the father of the syndrome; he had described it
as something new and of its own. Following several technical and medical advances and breakthroughs in
the twentieth century, in 1959 French physician Jerome Lejeune identified Down Syndrome as a
chromosomal abnormality. It was noted that there was 47 chromosomes in the cell of an afflicted person
versus the normal 46. It was later determined that there was a third chromosome 21, called trisomy-21
Down Syndrome occurs in about 1 in every 800 to 1000 births and has affected more than 350,000
lives in the US alone It is caused by the extra chromosome 21 when an embryo has three copies of
chromosome 21. Ninety-five percent of the time this is caused by disjunction during cell division. Due to
younger women’s higher fertility rate, 80% of Down Syndrome babies are born to women under age 35.
However, the chances of having a Down Syndrome baby increases with age of the parents.2
The phenotypes, or symptoms, of a Down Syndrome face are as follows: low muscle tone (weak
muscle structure), small nose, flat face, slanted eyes (upward) and abnormally shaped ears (figure 2) . Other
abnormal phenotypes include no second palm crease (figure 3) (unaffected person have two major palm
creases), hyperflexibility, pinkie fingers with only one flexion furrow (crease), epicanthal folds (folds of
skin around the eyes), excessive space between the big toe and second toe, and an oversized tongue, which
impends speech. 3
Person with Down Syndrome also are at increased risks for congenital heart defects, due to the
excess strain on their bodies from their condition, and also respiratory problems and obstructed digestive
tracts, as well as higher instance of childhood leukemia. Surprisingly, life expectancy is 55 years of age due
to medical breakthroughs and advancements. Unfortunately, 1 out of 4 Down Syndrome persons is affected
with Alzheimer’s Disease. Another problem facing them is that most have some level of mental retardation,
but not to excessive amounts. On the up side, with proper mental and physical stimulation, they can lead
normal lives. 2
Queries of the Literature
1. What tests are used for prenatal diagnosis?4
Diagnostic tests sample fetal cells and give a definitive diagnosis. Screening tests are relatively simple
tests that detect fetuses with Down syndrome. The Diagnostic tests used are amniocentesis or
chorionic villi sampling (CVS). With amniocentesis a needle is passed through the mother’s belly into
the womb to sample fetal cells in the amniotic fluid. Ultrasound is used to locate the fetus and the
placenta. The test is usually done between 14 and 18 weeks of pregnancy. Although fairly safe there is
a small risk of miscarriage. CVS samples cells from the chorionic villi, cellular projections from the
outer chorionic sack. It is done between 9 and 12 weeks. It also has similar risks. More recently
screening tests include maternal alpha-fetoprotein. The maternal alpha-fetoprotein test was initially
devised to screen for neural tube defects, such as spina bifida. A low level of alpha-fetoprotein has
been correlated with Down Syndrome and some other chromosome disorders. The test is estimated to
detect approximately 35% of fetuses with Down Syndrome as confirmed by amniocentesis.
The “Triple Test” measures a mother’s blood levels of human chorionic gonadotropin (hCG),
maternal serum alpha-fetoprotein (MSAFP) and unconjugated estriol. The three results are adjusted by
a computer program to give an estimate of the risk of having a fetus with Down Syndrome. Studies so
far suggest a detection rate of 55-60% after confirmation by amniocentesis. Because the accuracy rate
of all of the serum tests depends on accurately knowing the number of weeks of pregnancy, a positive
test should have an ultrasound done to confirm the date of pregnancy. If the adjusted test results are
still positive, then either amniocentesis or chorionic villi sampling should be done.
2. Do people with Down Syndrome have normal life expectancies?
No. Generally, life expectancy is reduced 10-20 years. Some people with Down Syndrome, however,
have been known to live into their 80’s.
3. Are people with Down Syndrome more susceptible to Alzheimer’s disease?5
Possibly, although the final answer on this is not yet available. Although it is true that some of the
Alzheimer-like changes in the physical brain occur in most, if not all, people with Down Syndrome as
they age, the clinical appearance of dementia does not always occur. The latest thinking is that because
of premature aging, Alzheimer’s dementia that does develop comes on at an earlier age however the
incidence of dementia may or may not be increased. It wold be wrong to assume that an adult with
Down Syndrome who appears to have developed dementia does in fact have Alzheimer’s dementia.
There are many medical and psychiatric conditions that may mimic dementia. This is particularly true
if the individual is less than 40 or 50 years of age.
4. Are ethical issues involved when dealing with a Down Syndrome pregnancy?
Besides the medical issues involved, there are obvious ethical issues involved. The results of the
testing are most likely used for one of two purposes. The couple may use the information to decide
whether or not to have an abortion of the information may be used to prepare for the delivery.
Although groups recommending routine use of the blood tests also recommend counseling, they do not
specifically address the type of counseling. Counseling should provide the couple with all information
and contact either with families who have a child with Down Syndrome and/or with people with Down
5. Are there medical treatments for Down Syndrome?
Although there have been proposed medical treatments for Down Syndrome, none of them have been
proven effective. These treatments have included thyroid hormone, pituitary extract, glutamic acid,
dimthyl sulfoxide, Sicca cell therapy, five-hydrooxytryptophan, and various vitamin and mineral
therapies. Sicca cell therapy has been shown by several reports to be dangerous. Careful studies
looking at the use of vitamin supplementation showed no benefit. An early study suggested that hey
did, however, when a follow up study was done to look for a placebo effect, no benefit was found.
Figure 1 – Figure 2 - Typical Figure 3 - Hand of a
Karyotype of Down face of Down Down Syndrome child
1. Web Address: http://odur.let.rug.nl/~usa/B/langdon/langdon.htm
2. Web Address: http://php.indiana.edu/~srogina/downsynd/
3. Compilation: Ostrowski, R., McNally, L. “Medical Genetics”.
4. Haddow, Palomaki, Knight, Williams, Pulkinen, Canick, et al., 1992
5. Web Address: http://www.alz-sioux.org/down01.htm