Early warning of birth defects Genetic testing gives couples time to evaluate risks

Imagine giving birth to a beautiful baby, only to see it decline and die from a fatal disease.

That's the plight of parents whose children are born with an inherited condition known as Tay-Sachs disease.


But thanks to genetic testing, parents can know if they're at risk for passing on Tay-Sachs to offspring -- and do something about it prior to a pregnancy.

Because of voluntary genetic testing before a couple decided to have a child -- or before marriage -- couples at high risk for having a child with the fatal disease found out prior to a pregnancy.


As a result, there has been a 60 percent to 85 percent drop in the number of children born with Tay-Sachs, says Dr. Celia I. Kaye, professor and deputy chief of the pediatrics department at the University of Texas Health Science Center at San Antonio.

Although Tay-Sachs can occur in any family, descendants of Ashkenazi Jews -- those who trace their families to Central and Eastern Europe -- are especially vulnerable. Estimates are that 1 out of 25 American Jews carry the gene -- about 10 times the rate among other groups.

Despite the brave new world of genetics testing, few families have to worry about their offspring having an inherited disorder.

"Ninety-seven percent of all babies born alive are normal," says Dr. Kaye.

Every one of us has 50,000 to 100,000 genes, she says.

"Even normal individuals can carry genes which are harmful," Dr. Kaye says. "All of us carry about six or eight genes which would be lethal if we carried them in a double dose."

However, that gene may be passed on to another generation, she says.

Many hundreds of genes are found on each chromosome within the body. To perform genetic testing, doctors merely have to take a sample of blood or other easily obtainable human tissue.


They can then look for chromosomal abnormalities using powerful microscopes.

Yet, even state-of-the-art genetics can't guarantee a happy ending to the pregnancy.

"People have unrealistic ideas sometimes about what is possible in the field of human genetics," says Dr. Mary Jo Harrod, associate professor at the University of Texas Southwestern Medical School at Dallas' obstetrics and gynecology department.

"They expect every pregnancy to result in a normal, healthy baby 100 percent of the time. We can't guarantee they will all turn out to be normal."

Experts in genetic testing use Tay-Sachs as an example of how their science can be of benefit.

"Tay-Sachs children usually die in early to middle childhood," says Dr. Kaye. "This is a disorder where the testing of carriers is possible."


That's important because Tay-Sachs disease is "one of the most tragic inherited conditions," says a fact sheet from the March of Dimes.

The infant gradually becomes blind, paralyzed and increasingly unaware of the surrounding world until it dies around 3 or 4 years of age. There is no cure and no treatment that will prevent the disease from running its course.

Of 640,000 Jewish couples voluntarily screened for Tay-Sachs from 1970 through 1987, about 24,000 carriers were detected. These people carry one gene for Tay-Sachs. If a carrier marries someone who is not a carrier of the Tay-Sachs gene, none of their children will have the disease, although each child has a 50-50 chance of being a carrier.

When carriers marry

But if a Tay-Sachs carrier marries another carrier, there is a 1-in-4 chance any child produced by this couple will have the disease. There's the same chance the child will be healthy, and a 2-in-4 chance the child will be a carrier.

The voluntary screening, Dr. Kaye says, identified 729 couples at risk -- meaning both were carriers of Tay-Sachs.


In many cases, Dr. Kaye says, couples were tested and counseled prior to marriage. Genetic counselors helped the couples clarify their options.

"They can choose not to get married, they can choose not to have children, they can choose to have artificial insemination or they can chose prenatal diagnosis," she says.

"There are still some Tay-Sachs babies born," Dr. Kaye says. "Some couples have made the decision to go ahead with the birth of an abnormal baby."

But genetics allowed them to make an informed decision.

Experts say genetic screening can be helpful in similar cases where inherited diseases, including sickle-cell anemia, run in families.

According to the March of Dimes, doctors have identified some 3,000 known causes of birth defects. Many -- but not all -- are caused by heredity.


"If you already know something's going on in your family, it's a good idea to find out what the risks are," says Dixie Skeen, coordinator of the Genetic Screening and Counseling Services office in Waco, Texas. She says people may come to her agency to get tested and receive counseling.

Risk assessment

A routine prenatal risk assessment will consider the parents' age and health, ethnic group and family medical history. If the mother's age is 35 or older when she delivers the baby, there is an increased risk of chromosomal abnormality, Dr. Harrod says.

"In general, 35 has been selected as a major age," when women should be tested for possible problems, she says. "There's enough of an increased risk that we need to make patients aware of that and offer some sort of testing."

In coming years, such problems may be more common, as women wait longer to start their families.

"We are seeing more and more pregnancies in women who are over 40," Dr. Harrod says. "When you get up to 46 or 47, you're looking at a very significant risk of chromosomal abnormality."


The father's age matters, as well, Dr. Harrod says.

One reason is that many men work in occupations that expose them to radiation or chemicals. This may cause a new mutation -- something happening to a gene because of exposure, not heredity.

Couples who suffer multiple miscarriages are usually referred for genetic screening to rule out chromosomal abnormalities.

"Ninety-eight percent of these tests come back normal," Ms. Skeen says. "There's no higher risk of most couples' having children born with defects."

The March of Dimes says that 1 out of every 14 babies born begins life with a birth defect. Each year, parents of about 250,000 American babies learn that their child has been born with a birth defect.



During pregnancy, prenatal tests can detect problems ranging from chromosomal errors and genetic disorders to heart defects. Prenatal and diagnostic tests may include:

* Alpha-fetoprotein (AFP): A screening test that measures the amount of AFP, a protein normally produced by a fetus as it grows. High levels may indicate spina bifida, neural tube defects, abdominal wall defects or the presence of twins. Abnormally low levels may mean Down syndrome.

* Ultrasound or sonogram: Sound waves show the physical outlines of the fetus on a screen, helping determine the fetus' age and whether there are twins. It can detect malformations such as spina bifida, heart or kidney problems, or limb defects. There is no known risk of having this procedure performed.

* Amniocentesis: Done during the 12th to 16th week of pregnancy, amniocentesis detects chromosomal errors and some Single-gene disorders, such as Down syndrome. It can also tell the sex of the fetus, detect a neural tube defect and some metabolic disorders. Doctors use ultrasound to see the fetus on a screen, then insert a thin needle into the mother's abdomen to withdraw two to three table spoons of amniotic fluid. There is a small risk, less than 1 in 200, of infection or miscarriage. Results are highly accurate, though many conditions cannot be detected.

* Chorionic villi sampling (CVS): A new test done in the eighth to 11th week of pregnancy. A tiny tissue sample is taken from outside the sac where the fetus develops, through either a small needle or tube. The tissue is analyzed for chromosome disorders and certain gene conditions. This is slightly less accurate than amniocentesis. The risk of miscarriage is one in 50 to 100 cases.