Older fathers appear to raise risks of genetic disorder

Older fathers appear to raise risks of genetic disorder - Print Version - International Herald Tribune 19/09/07 20.04
http://www.iht.com/bin/print.php?id=4748536 Page 1 of 2
Older fathers appear to raise risks of genetic disorders
By Roni Rabin
Wednesday, February 28, 2007
When it comes to fertility and the prospect of having normal babies, it has always been assumed
that men have no biological clock — that unlike women, they can have it all, at any age.
But mounting evidence is raising questions about that assumption, suggesting that as men get
older, they face an increased risk of fathering children with abnormalities. Several recent studies
are starting to persuade many doctors that men should not be too cavalier about postponing
marriage and children.
Until now, the problems known to occur more often with advanced paternal age were so rare they
received scant public attention. The newer studies were alarming because they found higher rates
of more common conditions — including autism and schizophrenia — in offspring born to men in
their middle and late 40s. A number of studies also suggest that male fertility may diminish with
age.
"Obviously there is a difference between men and women; women simply can't have children after
a certain age," said Dr. Harry Fisch, director of the Male Reproductive Center at New York-
Presbyterian Hospital/Columbia University Medical Center and the author of "The Male Biological
Clock."
"But not every man can be guaranteed that everything's going to be fine," Fisch said. "Fertility will
drop for some men, others will maintain their fertility but not to the same degree, and there is an
increased risk of genetic abnormalities."
It's a touchy subject. "Advanced maternal age" is formally defined: women who are 35 or older
when they deliver their baby may have "AMA" stamped on their medical files to call attention to
the higher risks they face. But the concept of "advanced paternal age" is murky. Many experts are
skeptical about the latest findings, and doctors appear to be in no rush to set age guidelines or
safety perimeters for would-be fathers, content instead to issue vague sooner-rather-than- later
warnings.
"The problem is that the data is very sparse right now," said Dr. Larry Lipschultz, a specialist in
the field of male infertility and a past president of the American Society for Reproductive Medicine.
"I don't think there's a consensus of what patients should be warned about."
And many men maintain their fertility, said Dr. Rebecca Sokol, president of the Society of Male
Reproduction and Urology. "If you look at males over 50 or 40, yes, there is a decline in the
number of sperm being produced, and there may be a decline in the amount of testosterone,"
Sokol said. But by and large, she added, "the sperm can still do their job."
Some advocates, however, welcome the attention being paid to the issue of male fertility, saying it
is long overdue.
"The message to men is: 'Wake up,'" said Pamela Madsen, executive director of the American
Fertility Association, a U.S. education and advocacy group. "It's not just about women anymore,
it's about you, too."
Analyses of sperm samples from healthy men have found changes as men age, including
increased fragmentation of DNA, and some studies outside the United States have noted
increased rates of some cancers in children of older fathers.
Geneticists have been aware for decades that the risk of certain rare birth defects increases with
the father's age. One of the most studied of these conditions is a form of dwarfism called
achondroplasia, but the list also includes neurofibromatosis, the connective tissues disorder Marfan
syndrome, skull and facial abnormalities like Apert syndrome, and many other diseases and
abnormalities.
Some studies suggest that the risk of sporadic single-gene mutations may be four to five times
higher for fathers who are 45 and older, compared with fathers in their 20s, said Dr. Joe Leigh
Simpson, president-elect of the American College of Medical Genetics. Overall, having an older
father is estimated to increase the risk of a birth defect by 1 percent, against a background 3
percent risk for a birth defect, he said.
Even grandchildren may be at greater risk for some conditions that are not expressed in the
daughter of an older father, according to the American College of Medical Genetics. These include
Duchenne muscular dystrophy, some types of hemophilia and fragile-X syndrome.
A recent study on autism attracted attention because of its striking findings. Researchers analyzed
a large Israeli military database to determine whether there was a correlation between paternal
age and the incidence of autism and related disorders. It found that children of men who became
a father at 40 or older were 5.75 times as likely to have an autism disorder as those whose fathers
were younger than 30.
"Until now, the dominant view has been, 'Blame it on the mother,'" said Dr. Avi Reichenberg, the
lead author of the study, published in September in The Archives of General Psychiatry. "But we
Older fathers appear to raise risks of genetic disorders - Print Version - International Herald Tribune 19/09/07 20.04
http://www