120
U N I T 1
Cell and Tissue Function
Based on studies conducted in the 1970s, including
one sponsored by the National Institutes of Health and
Human Development, it has been estimated that the
47,XXY syndrome is one of the most common genetic
abnormalities known, occurring as frequently as 1 in
500 to 1000 male births.
32
Although the presence of
the extra chromosome is fairly common, the signs and
symptoms of Klinefelter syndrome are relatively uncom-
mon. Many men live their lives without being aware that
they have an additional chromosome. For this reason, it
has been suggested that the term
Klinefelter syndrome
be replaced with
47,XXY male
.
Adequate management of Klinefelter syndrome
requires a comprehensive neurodevelopmental evalu-
ation. Men with Klinefelter syndrome have con-
genital hypogonadism, which results in inability to
produce normal amounts of testosterone accompa-
nied by an increase in hypothalamic gonadotrophic
hormones (see Chapter 39). Androgen therapy is usu-
ally initiated when there is evidence of a testoster-
one deficit. This may begin as early as 12 to 14 years
of age.
34
Because gynecomastia predisposes to breast
cancer, breast self-examination should be encouraged
for men with Klinefelter syndrome. Infertility is com-
mon in men with Klinefelter syndrome due to a decrease
in sperm count. If sperm are present, cryopreservation
may be useful for future family planning.
Disorders Due to Environmental
Influences
The developing embryo is subject to many nongenetic
influences. After conception, development is influenced
by the environmental factors that the embryo shares with
the mother. The physiologic status of the mother—her
hormone balance, her general state of health, her nutri-
tional status, and the drugs she takes—undoubtedly influ-
ences fetal development. For example, diabetes mellitus
is associated with increased risk of congenital anomalies.
Smoking is associated with lower than normal neona-
tal weight. Alcohol consumption can cause fetal abnor-
malities. Some agents cause early abortion. Measles and
other infectious agents cause congenital malformations.
Other agents, such as radiation, can cause chromosomal
and genetic defects and produce developmental disor-
ders. Chart 6-1 lists some common agents.
Period of Vulnerability
The embryo’s development ismost easilydisturbedduring
the period when differentiation and development of the
organs are taking place. This time interval, which is
often referred to as the period of
organogenesis
, extends
from day 15 to day 60 after conception. Environmental
influences during the first 2 weeks after fertilization
may interfere with implantation and result in abortion
or early resorption of the products of conception. Each
organ has a critical period during which it is highly sus-
ceptible to environmental derangements
2,3,48
(Fig. 6-13).
Often, the effect is expressed at the biochemical level
just before the organ begins to develop. The same agent
may affect different organ systems that are developing
at the same time.
Teratogenic Agents
A teratogenic agent is an environmental agent that pro-
duces abnormalities during embryonic or fetal devel-
opment. Maternal disease or altered metabolic state
also can affect the environment of the embryo or fetus.
Theoretically, environmental agents can cause birth
defects in three ways: by direct exposure of the pregnant
woman and the embryo or fetus to the agent; through
exposure of the soon-to-be-pregnant woman with an
agent that has a slow clearance rate such that a tera-
togenic dose is retained during early pregnancy; or as
a result of mutagenic effects of an environmental agent
that occur before pregnancy, causing permanent dam-
age to a woman’s (or a man’s) reproductive cells. The
developing embryo is subject to many nongenetic influ-
ences. After conception, development is influenced by
the environmental factors that the embryo shares with
the mother.
Radiation
Radiation is teratogenic and mutagenic, and there is
the possibility of effecting inheritable changes in genetic
materials. Heavy doses of ionizing radiation have been
shown to cause microcephaly, skeletal malformations,
and intellectual disability. There is no evidence that diag-
nostic levels of radiation cause congenital abnormalities.
Because the question of safety remains, however, many
agencies require that the day of a woman’s last menstrual
SUMMARY CONCEPTS
■■
Chromosomal disorders result from a change in
chromosome structure or number.They reflect
events that occur at the time of meiosis, such as
defective movement of an entire chromosome
or breakage of a chromosome with loss, gain, or
translocation of genetic material.
■■
A change in chromosome number is called
aneuploidy. Monosomy involves the presence
of only one member of a chromosome pair as
is seen inTurner syndrome, in which there is
monosomy of the X chromosome in females.
Polysomy refers to the presence of more than
two chromosomes in a set, as occurs in
Klinefelter syndrome, which involves polysomy
of the X chromosome in males.Trisomy 21
(i.e., Down syndrome) is the most common
disorder of the autosomal chromosomes, and
occurs in both sexes.
