A First for Genetic Testing
A recommendation by influential physicians’ groups that expectant parents receive counseling about genetic testing for cystic fibrosis--an incurable disease that’s often fatal by early adulthood--brings the era of genetic testing a step closer to many families.
The new guidelines mean that more parents will learn early in a pregnancy that a woman is at risk of bearing a child with cystic fibrosis. That knowledge could lead to earlier and possibly more effective treatments for newborns with the disease. But the genetic tests also raise difficult ethical issues for doctors and expectant parents, who in some cases might decide to terminate a high-risk pregnancy after receiving unfavorable test results, experts acknowledge.
The recommendation was made last month by two medical organizations, the American College of Obstetricians and Gynecologists and the American College of Medical Genetics, after years of debate and study.
The guidelines state that doctors should advise couples about a test, known as carrier screening, to determine if an individual carries the gene that causes CF. This counseling could be offered at the time a woman sees a doctor for pregnancy planning or during the first office visit after pregnancy.
If the prospective parents opted for testing, the woman would have a blood or saliva test to identify the defective gene. If she were found to carry the gene, the father could then also undergo testing to determine his carrier status. Both parents must carry the gene for the baby to have cystic fibrosis, and in such cases the child has a 25% chance of having the disease. Some parents might decide to terminate the pregnancy if subsequent testing of the fetus shows it will have cystic fibrosis.
The couple’s decision, however, could be complicated by several factors. The tests, for example, cannot determine how serious the disease will be; there are mild to severe forms of cystic fibrosis.
And no test can predict how future medical advances may improve treatments for the disease. Scientists are hopeful that better medications and the potential for gene therapy treatments will improve life expectancies for cystic fibrosis patients.
One reason for genetic testing would be to consider an abortion if a child carried the gene, said Michael Watson, executive director of the American College of Medical Genetics. “But there is some question about using the test for that reason. ... Kids with CF used to die much younger than they do now.” On the other hand, he said, some couples may consider any form of the disease too severe to continue the pregnancy.
There is no cure for cystic fibrosis, although treatment for its symptoms has improved dramatically in the last decade. The average life expectancy for those with the disease is about age 30. Most people with CF require close medical supervision and often need daily treatments to clear mucus from their lungs.
Doctors who helped draw up the new guidelines emphasized that they are not recommending testing for parents but simply that potential parents be informed that the test is available and why, said Dr. Michael T. Mennuti, a Philadelphia obstetrician. “The decision is their decision,” he said. “It’s a complex and personal choice.”
That sentiment was echoed by the Cystic Fibrosis Foundation, the nation’s leading advocacy group for the disease. A foundation official was reluctant to comment on the physician groups’ recommendations. “We believe testing is a very personal decision,” says Suzanne Pattee, vice president for public policy and patient affairs. “We don’t believe our organization should impose its views on anyone.”
Cystic fibrosis is the most common recessive genetic disorder in Caucasians, affecting about one in every 3,300 babies born. It is less common in other ethnic groups. Individuals with CF have a defect in the chloride transport mechanism in the cells. This results in the thick mucus in the lungs and pancreas that are the disease’s major characteristics.
The gene responsible for CF was identified in 1989, and carrier screening tests were developed a short time later. The test, however, was usually recommended only for people known to be at high risk for having children with CF, such as people with relatives who have the disease.
It is not uncommon for certain groups to be offered screening tests for a specific gene defect. Ashkenazi Jews, for example, often choose to undergo screening for the gene that causes Tay-Sachs disease in newborns. But the CF carrier screening recommendation is the first to target a broad population, Watson said.
The recommendation comes four years after the National Institutes of Health, the federal government’s medical branch, urged that prospective parents be offered genetic testing for cystic fibrosis. It has taken four years to implement the program because of the complexities involved, Watson said.
The screening program is complicated because the accuracy of the test varies among different ethnic groups; it is not 100% accurate for any group. Since the CF gene was first identified, more than 900 mutations, or variations, of the gene have been identified. One variation, for example, accounts for 70% of all CF mutations in Caucasians but only 30% of those found in Ashkenazi Jews.
In the last several years, geneticists have worked to identify a carrier-screening test that would identify a panel of gene mutations responsible for the most severe forms of the disease. Even so, the current panel of CF gene mutations is expected to pick up only 57% of mutations in Latinos. Even less is known about the gene mutations responsible for cystic fibrosis in Asian Americans.
Geneticists were also reluctant to act on the 1997 NIH recommendation for screening until they could ensure that testing labs were, at a minimum, screening for the most serious CF gene mutations.
The test costs between $180 and $400 and may be covered by insurance only if there is a family history of the disease.
The recommendation includes advice for labs conducting CF screening. Moreover, the American College of Obstetricians and Gynecologists has published two brochures to help patients understand the test. But some experts worry that couples may not always be appropriately counseled about the implications of a positive screening test.
For example, if both prospective parents have a positive test, it is imperative that they understand that the child has a 25% risk of having CF and that they can undergo prenatal testing, using amniocentesis or chorionic villus sampling, to determine with certainty if the fetus has the disease.
Couples also should be counseled that carrier screening may turn up a condition linked to the CF gene mutation that causes infertility in men. However, males with this condition, called congenital bilateral absence of the vas deferens, do not have cystic fibrosis and are otherwise healthy.
“That was one was of the more difficult things we had to deal with in developing the panel,” said Watson. “There are variations in the gene that can mean just infertility. Our goal is not to identify those persons in that panel. But the people conducting the test may feel obligated to tell couples everything.”
Couples who learn their child will have cystic fibrosis also should be counseled about treatments for the disease that can begin shortly after birth. Most people with CF are diagnosed within the first year of life, but only after symptoms have emerged. Experts believe that children may fare better with earlier treatment.
Some states, including California, are considering adding cystic fibrosis to the list of inherited conditions that infants are tested for shortly after birth. Some couples may choose to bypass prenatal carrier screening if informed that the disease could be picked up early in their child’s life.
“The argument for doing newborn screening is to improve their outcome,” Watson said. “As cystic fibrosis therapies improve, I think we might see the pendulum swing away from carrier testing to testing and treating the newborn.”
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Testing for Cystic Fibrosis
Cystic fibrosis is an inherited disorder that is more common in certain ethnic groups. When both the father and mother carry the gene that causes cystic fibrosis, there is a 25% chance their child will have the disease. Recently, two major physicians’ organizations recommended that pregnant couples, or those planning a pregnancy, be offered the blood test that detects the presence of the CF gene. The accuracy of the test, however, varies depending on the individual’s ethnicity.
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Ethnic group Incidence Accuracy European Caucasian 1 in 3,300 people 80% Ashkenazi Jew 1 in 3,300 97% Latinos 1 in 8,464 57% African American 1 in 16,900 69% Asian American 1 in 32,400 *
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* Insufficient data available.
Source: National Institutes of Health
