118
U N I T 1
Cell and Tissue Function
accompanying congenital heart defects and an increased
risk of gastrointestinal malformations. Approximately
1% of persons with trisomy 21 Down syndrome have
mosaicism (i.e., cell populations with the normal chromo-
some number and cell populations with trisomy 21); these
persons may be less severely affected. Of particular con-
cern is the much greater risk of development of acute leu-
kemia among children with Down syndrome—10 to 20
times greater than that of other children.
3
With increased
life expectancy due to improved health care, it has also
been found that there is an increased risk of Alzheimer
disease among older persons with Down syndrome.
In the past few years, unprecedented breakthroughs
have been made in the treatment of Down syndrome.
These include the development of interventional and
educational strategies to help affected individuals achieve
their employment and independence goals based on their
full potential. Several studies to determine safe and effec-
tive drugs to improve cognitive ability have been initiated
(Down Syndrome Research and Treatment Foundation
/).
Several prenatal screening tests can help determine the
risk of having a child with Down syndrome.
33
The most
commonly used are blood tests that measure maternal
serum levels of
α
-fetoprotein, human chorionic gonado-
tropin (hCG), unconjugated estriol, inhibin A, and preg-
nancy-associated plasma protein A (PAPP-A, see section
on prenatal screening and diagnosis). The results of three
or four of these tests, together with the woman’s age,
often are used to determine the probability of a pregnant
woman having a child with Down syndrome. Another
test, fetal nuchal translucency (sonolucent space on the
back of the fetal neck), uses ultrasonography and can be
performed between 10 and 13 weeks’ gestation. The fetus
with Down syndrome tends to have a greater area of trans-
lucency compared with a chromosomally normal infant.
The nuchal translucency test is usually used in combina-
tion with other screening tests. The current standard for
determining the presence of Down syndrome in the fetus
is through chromosome analysis using chorionic villus
sampling, amniocentesis, or percutaneous umbilical blood
sampling. More recently, non-invasive screening for fetal
chromosomal abnormalities using cell-free DNA obtained
through a maternal blood draw has become available.
Numeric Disorders Involving Sex
Chromosomes
Chromosomal disorders associated with the sex chro-
mosomes are much more common than those related
to the autosomes, save for trisomy 21. Furthermore,
imbalances (excess or deletions) are much better toler-
ated than those involving the autosomes. This is related
in large part to two factors that are peculiar to the
sex chromosomes: (1) the inactivation of all but one
X chromosome and (2) the modest amount of genetic
material that is carried on the Y chromosome.
Although girls normally receive both a paternal and
a maternal X chromosome, the clinical manifestations
of X-chromosome abnormalities can be quite vari-
able because in somatic cells of females only one X
chromosome is transcriptionally active while the other
chromosome is inactive.
1
The process of X inactivation,
which is random, occurs early in embryonic life and is
usually complete at the end of the first week of develop-
ment. After one X chromosome has become inactivated
in a female, all cells descended from that cell have the
same inactivated X chromosome. Although much of one
X chromosome is inactivated in females, several regions
contain genes that escape inactivation and continue to
be expressed by both X chromosomes. These genes may
explain some of the variations in clinical manifesta-
tions seen in cases of numerical abnormalities of the X
chromosome, such as Turner syndrome.
Turner Syndrome
Turner syndrome describes an absence of all (45,X/0)
or part of one of a female’s two X chromosomes.
2,3,34–42
Some women may display a mosaicism with one or more
additional cell lines. This disorder affects approximately
1 of every 5000 live births, and it has been estimated
that almost all fetuses with the 45,X/0 karyotype are
spontaneously aborted during the first trimester.
2
Characteristically, the girl with Turner syndrome
is short in stature, but her body proportions are nor-
mal (Fig. 6-11). Because of the absence of the ovaries,
she does not menstruate and shows no signs of sec-
ondary sex characteristics. There are variations in the
Small stature
Low posterior hairline
and webbed neck
Coarctation of
aorta and
bicuspid
aortic valve
Poor breast
development
Broad chest with
widely spaced nipples
Wide carrying
angle of arms
Ovarian dysgenesis
with primary
amenorrhea, estrogen
and progesterone
deficiencies, and
infertility
Multiple
pigmented nevi
Retardation
of bone age
Lymphedema of
hands and feet
at birth and later
FIGURE 6-11.
Clinical features ofTurner syndrome.
