Down syndrome is a chromosomal abnormality. It is the most frequent
form of mental retardation and is characterised by well-defined, distinctive
phenotypic features and natural history. An error in cell development results
in forty-seven chromosomes rather than the usual forty-six. There are three
major types of Down syndrome. About ninety-five percent of individuals with
Down syndrome have Trisomy 21.
There is also Translocation and
Mosaicism. Down syndrome can also be referred to as Mongolism, the
condition is named for John Langdon Down. Down was the superintendent of
an asylum for children with mental retardation in Surrey, England when he
made the first distinction between children who were cretins and what he
referred to as “Mongoloids.” Down based this unfortunate name on his notion
that these children looked like people from Mongolia, who were thought then
to have an arrested development. This ethnic insult came under fire in the
1960s from Asian genetic researchers, and the term was dropped from
scientific use. Instead, the condition became “Down’s syndrome.
” In the
1970s, an American revision of scientific terms changed it simply to “Down
syndrome,” while it still is called “Down’s” in Europe.
In the first part of the twentieth century, there was much speculation of
the cause of Down syndrome. The first people to speculate that it might be
due to chromosomal abnormalities were Waardenberg and Bleyer in the
1930s. But it wasn’t until 1959 that Jerome Lejeune and Patricia Jacobs,
working independently, first determined the cause to be trisomy of the 21st
chromosome. Cases of Down syndrome due to translocation and mosaicism
were described over the next three years.
The estimated incidence of Down syndrome is between 1 in 1,000 to 1
in 1,100 live births.
Each year approximately 3,000 to 5,000 children are born
with this chromosome disorder. It is believed there are about 250,000 families
in the United States who are affected by Down syndrome.
Mode of Inheritance
Although many theories have been developed, it is not known what
actually causes Down syndrome. Some professionals believe that hormonal
abnormalities (X-rays, viral infections, immunologic problems, or genetic
predisposition) may be the cause of the improper cell division resulting in
It has been known for some time that the risk of having a child with
Down syndrome increases with advancing age of the mother. For example
the older the mother, the greater the possibility that she may have a child with
However, most babies with Down syndrome (more than 85
percent) are born to mothers younger than 35 years. Some investigators
reported that older fathers may also be at an increased risk of having a child
with this condition. It is well known that the extra chromosome in trisomy 21
could either originate in the mother or the father. Most often, however, the
extra chromosome comes from the mother.
In Down syndrome, 95 percent of all cases are caused by this event:
one cell has two 21st chromosomes instead of one, so the resulting fertilised
egg has three 21st chromosomes. Recent research has shown that in these
cases, approximately 90 percent of the abnormal cells are the eggs.
four percent of all cases of trisomy 21 are due to Robertsonian Translocation.
In this situation, two breaks occur in separate chromosomes, usually the 14th
and 21st chromosomes. There is rearrangement of the genetic material so that
some of the 14th chromosome is replaced by extra 21st chromosome. So
while the number of chromosomes remain normal, there is a triplication of the
21st chromosome material. Some of these children may only have triplication
of part of the 21st chromosome instead of the whole chromosome, which is
called a partial trisomy 21. Translocations resulting in trisomy 21 may be
inherited, so it’s important to check the chromosomes of the parents in these
incidences to see if either may be a “carrier.
The remaining cases of trisomy 21 are due to mosaicism. These people
have a mixture of cell lines, some of which have a normal set of
chromosomes and others which have trisomy 21. In cellular mosaicism, the
mixture is seen in different cells of the same type. In tissue mosaicism, one
set of cells .