[Homestead] A "healthy" lifestyle does nothing for too commn genetic defects
tvoivozd at infionline.net
Tue Aug 31 22:25:30 EDT 2004
The Havoc of an Undetected Extra Chromosome
*By JANE E. BRODY*
Published: August 31, 2004
Sam's parents began to suspect something was not quite right when at age
2, their son still was not walking and he said nothing that made any sense.
Laboratory and neurological tests showed no abnormalities. But a genetic
test revealed that Sam's cells contained an extra copy of the X
chromosome. Instead of having 46 chromosomes, including one copy of each
of the sex chromosomes, X and Y, the normal complement for a boy, each
of Sam's cells had 47 chromosomes, with two X's and one Y, a genetic
abnormality commonly called Klinefelter's syndrome.
A doubling of the X chromosome, according to a government study of
40,000 infants in the 1970's, occurs once in every 500 to 1,000 male
births, making it one of the most common genetic abnormalities. It is a
leading genetic cause of male infertility. Yet nearly two-thirds of boys
and men who have Klinefelter's do not know it, and many live out their
lives never suspecting that they have an extra chromosome.
As Sam's mother noted in an interview, doctors, too, are often in the
dark. "None of our doctors had ever heard of it," she said. "We did a
lot of research on our own."
Sam is now 13, and through special education services, he has been able
to keep up academically. His speech is now normal and while he has had
some social problems, he loves sports and participates in athletics, his
mother said. As he enters puberty, his levels of testosterone are being
checked regularly by an endocrinologist. When they begin to drop below
normal, he will receive regular testosterone treatments.
*Array of Symptoms*
The syndrome was first identified in 1942 by Dr. Harry Klinefelter and
colleagues at Massachusetts General Hospital in Boston, and its genetic
root was discovered in the late 1950's. Dr. Klinefelter described
symptoms that included enlarged breasts, small testes, sparse facial and
body hair and an inability to produce sperm.
Later studies revealed other common complaints: delayed speech and motor
development; difficulty learning to read and write; very long legs; a
rounded body type; decreased muscle mass; a tendency to become
overweight; an increased risk of diabetes and osteoporosis; a small
penis; and, eventually, a loss of potency.
While overall intellectual abilities are not affected (the I.Q. scores
of people with Klinefelter's are only slightly lower than average), XXY
males often experience deficits in specific cognitive functions,
including language, concept formation, and problem solving, that are
similar to those in dyslexic children.
After age 25, about 70 percent of patients complain of decreasing libido
and potency, and normal beard growth is present in only about a fifth of
patients, wrote Dr. Fabio Lanfranco, and colleagues at the Institute of
Reproductive Medicine at the University of Münster in Germany, in a
recent article in the journal The Lancet.
Depression, difficulty following through on goals, unusual fatigue and
sudden mood swings also often occur in XXY men and boys. There is,
however, no increase in psychiatric disturbances, criminal behavior or
Many of the symptoms of Klinefelter's, especially those noted at puberty
and beyond, result from a deficiency of testosterone, which occurs in
about 80 percent of XXY males after the age of 15. But the expression of
these symptoms varies widely, which accounts in part for why so many men
and boys with an extra X chromosome go undetected.
Once the genetic abnormality is diagnosed, many of the symptoms can be
reversed by regular testosterone treatments starting at puberty and
continuing for life, but failure of normal sperm production is not yet
Today, the term Klinefelter's syndrome has fallen out of favor because
its expression is so varied, and most medical researchers now refer to
affected boys and men simply as XXY males. Genetic studies have also
revealed many variants of the chromosomal mishap. Some boys are born
with three or more X chromosomes and one Y, some with two X's and two
Y's, and some with a combination of normal XY cells and abnormal XXY
cells. The latter are called genetic mosaics, and they tend to have
fewer symptoms than boys with only XXY cells.
These unusual combinations most often result from problems during the
formation of the egg or sperm that result in a failure of the two sex
chromosomes in a germ cell to separate properly.
*Treatment Can Help*
Early recognition and treatment of Klinefelter's syndrome can
significantly improve the patient's quality of life and prevent serious
consequences, Dr. Lanfranco and his team wrote. When testosterone levels
are low, they said, replacement therapy should be started as early as
possible. This results in increased masculinity, strength, libido, bone
mineral density and body hair. It also has a positive effect on mood and
behavior, improves goal-directed thinking and self-esteem and reduces
fatigue and irritability.
Testosterone therapy is also beneficial to the cardiovascular system,
though it has no effect on fertility. For Klinefelter patients with
bothersome breast development, surgical removal of excess tissue is
But long before testosterone replacement is needed, XXY boys can benefit
from special education classes, speech therapy and social behavior
training. For those seeking a solution to their infertility, it is now
possible in some cases to extract sperm directly from the testes and
insert them into an egg outside the woman's body. After fertilization
and early embryonic development, the embryos can be checked to be sure
they too do not contain the XXY defect before inserting them into the
womb. One expert has reported a live birth rate of 20 percent following
this procedure in 20 couples affected by XXY infertility.
Melissa Aylstock, the mother of an XXY boy and founder of KS &
Associates, publishes a newsletter with information about support
groups. The organization can be reached by writing to 11 Keats Court,
Coto de Caza, Calif. 92679, or calling toll-free (888) 999-9428. Its Web
site is www.genetic.org <http://www.genetic.org>.
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