Linda
Clark is 48 and seven months pregnant. With her daughter’s
twins.
A pregnancy could have killed Clark’s daughter, Heather
Torrens, because she has a severe form of a genetic disorder
called Marfan syndrome. The syndrome can make pregnancy too
risky.
It also can suddenly kill seemingly healthy young people.
People in their prime. Star athletes.
Some 200,000 Americans have the disorder, and many don’t
know it. Torrens did know, and knew that she could pass it
on to her children.
So she turned to a rarely done but promising technology that
could help thousands with Marfan’s.
She had embryos, created from in
vitro fertilization of her
eggs and her husband’s sperm, genetically
screened for
the disorder. Embryos free of Marfan syndrome were implanted
into her mother.
“Thousands of couples are carriers of this disease,” said
Dr. Sherman J. Silber, medical director of the Infertility
Dr. Sherman J. Silber, medical director of the Infertility
Center of St. Louis, located in Chesterfield. “Almost
all of them don’t know it, and many could benefit from
this technology.”
Marfan syndrome is a disorder of the connective tissue that
affects the skeleton, lungs, eyes, heart and blood vessels.
It’s caused by a defective gene. People who carry the
gene acquire the disease. If a parent has Marfan’s, the
child has a 50 percent chance of inheriting it. In 25 percent
of cases, however, the genetic mutation isn’t hereditary
but occurs spontaneously at conception.
Some of the disorder’s physical characteristics are
benign, such as being exceptionally tall, lean and loose-jointed.
But other traits are potentially fatal, such as a defect that
causes the aorta - the artery that carries blood away from
the heart - to enlarge and rupture, like a balloon that stretches
until it bursts. If not caught in time, the condition has a
50 percent mortality rate in the first 48 hours.
Marfan syndrome often goes undiagnosed. But if identified,
it can be treated medically and corrected surgically. With
intervention, people with the disorder have lived into their
70s or older.
Four years ago, when Torrens was 23, she was rushed into
emergency open-heart surgery to repair her aorta after it ruptured.
She almost died.
Today, she lives with an artificial heart valve and takes
blood thinners.
She learned when she was 6 that the disorder ran in her family,
on her father’s side. He also underwent an emergency
procedure to repair his aorta and had a heart valve replaced.
Torrens’ only sibling, a brother, also has Marfan syndrome.
He decided on elective surgery to repair heart defects.
Heather and her husband, David Torrens, wanted to spare their
children the medical complications and corrective surgeries
associated with Marfan’s.
“We’re just lucky to have the technology to pre-diagnose
Marfan’s so we can reduce the risk of passing it on to
a baby,” David Torrens said. The couple live in Monticello,
Ill., about 160 miles northeast of St. Louis.
Screening out disease
To test for Marfan syndrome, Silber, the local fertility
To test for Marfan syndrome, Silber, the local fertility specialist,
performed “polar body” analysis on 13 fertilized
eggs. A Chicago laboratory conducted further testing. Three
were free of Marfan syndrome.
Six other embryos came back with inconclusive test results
requiring additional testing with a procedure called blastomere
biopsy. Of the six, only three were still developing by the
third day.
Silber removed a single cell from each of the three viable
Silber removed a single cell from each of the three viable
embryos. At three days old, each was about the size of a grain
of sand. The cells were again sent to the Chicago laboratory,
where they also were analyzed.
Removing a single cell, called a blastomere, at that stage
of development doesn’t harm the embryo. A 3-day-old embryo
is made up of eight genetically identical cells. If one is
removed, the embryo can continue to develop normally.
Genetic
screening for Marfan’s is done indirectly because no
single test exists to screen for it.
Linked markers, or DNA fingerprints for Marfan’s,
on chromosome 15 were identified by comparing the chromosomes
of Heather Torrens, her brother and her father - all of whom
have Marfan syndrome - with David Torrens, who does not.
Three unaffected embryos were implanted into Clark in the
hope that at least one would develop. Two did.
Two other embryos
- both with the disorder - were frozen. The rest of the 13
embryos failed to develop normally, which is not an unusual
number.
Silber said the surviving embryos won’t be destroyed.
“It’s
not unrealistic to think there could be treatments for such
embryos based on current or future research,” he said.
Silber was one of the early developers of pre-implantation
Silber
was one of the early developers of pre-implantation
genetic diagnosis, dating back to his work with cystic fibrosis
in Belgium in 1993.
Marfan syndrome is one of about 3,000 single-gene defects.
Other single-gene diseases that can be screened for - and eliminated
- include cystic fibrosis, muscular dystrophy, sickle cell
anemia and Tay-Sachs disease.
The technology doesn’t come cheap and isn’t covered
by health insurance. The Torrens paid $20,000 out-of-pocket.
Not
everyone is comfortable with technology that allows genetic
screening of embryos.
Medical ethicist Dr. Stephen Lefrak agrees that screening
for disease falls within the ethical realm of medicine. But
he fears that the technology one day could be used to create
so-called designer babies.
“ At exactly what point does this particular process
step over the line?” asked Lefrak, a professor of medicine
at Washington University School of Medicine. “Is it OK
if my wife and I use it to find only a boy to implant?”
Experts
have an ethical obligation, Lefrak said, to come up with ground
rules on what’s permissible and what isn’t.
Silber
doesn’t use pre-implantation genetic diagnosis to Silber
doesn’t use pre-implantation genetic diagnosis to screen
for gender.
The idea of genetic screening for Marfan’s is widely
discussed among families with the disorder.
“People are weighing advances in modern medicine that
allow someone to live a longer life with Marfan’s with
whether they want to use fertility technologies to avoid passing
on the gene,” said Carolyn Levering, president of the
National Marfan Foundation. “It’s an emotional
issue.”
Some couples have decided not to have children.
Others have opted for a natural pregnancy, preferring to
cope with the disorder if a child inherits it. Still others,
like
the Torrens, select genetic screening in an attempt to avoid
it altogether.
“Each case is so different,” Levering said. “Someone
who comes from a family where everyone died (of Marfan’s)
at 35 may feel differently than someone who comes from a family
with a mild manifestation.”
A family affair
For Linda Clark, the decision has been a labor of love.
At first, she said nothing as her daughter made the rounds
of obstetricians and fertility specialists to determine her
options for having a family. Clark didn’t want to interfere,
but she also knew a pregnancy would put her daughter’s
life in peril. If her daughter chose to go with a surrogate
mother, she wanted to be that person.
Without telling her daughter, Clark asked her own doctor
during an annual exam, if she was healthy enough to serve as
a surrogate mother and carry a baby to term. He said yes.
Afterward,
Clark sat down with her daughter.
“After we discussed all the options, I said, ‘Here’s
one possibility,’ and put it on the table,” Clark
recalled.
The offer came as a surprise to her daughter.
“I just about fell out of my chair,” said Torrens,
a part-time bank teller. “I thought it was amazing that
she was willing to do something like that.”
“It’s not that I have to have grandkids,” said
Clark, of Decatur, Ill. “But I’m also getting a
gift by helping to enlarge our family.”
Despite all her mother’s help, the pregnancy has not
been problem-free for Torrens.
She was hospitalized in July for two weeks - five days in
intensive care - after a procedure to remove eggs from her
ovaries caused her to bleed heavily into her abdomen. The problem
was a complication of Marfan syndrome.
Today, Torrens lives the unique life of a prospective mother
who is expecting twins but is not pregnant.
“The babies are kicking and flopping around,” she
said. In front of her, spread across the kitchen table, atop
the couple’s wedding pictures, were photos of the babies
taken when they were just embryos.
“I’d like to feel the babies kicking me in the
rib,” she said, and then laughed. “But a lot of
people say, ‘No, you’re doing it the right way!’”
Clark is expected to give birth in mid-March.
As that special day approaches, Clark expresses surprise
that people view the pregnancy as anything unusual.
"If you have a chance to give a child the best life you can,” she
said, “most people - if they really think about it -
would choose to do that.”
Front Page - St. Louis Post Dispatch
January 26, 2003
Heather’s mother delivered
Heather’s healthy twins (boy and girl) on February
13, 2003. Both children are normal without any genetic
trace of Marfan’s disease.
