Gene-based tests designed to indicate whether couples are at higher risk for having a baby with cystic fibrosis are causing confusion in some doctors' offices, prompting questions about whether genetic screening needs broader oversight.
The tests, for gene mutations that cause the life-shortening disease, have been used increasingly since fall 2001. That's when a leading physicians' organization recommended that they be offered to white couples of European and Ashkenazi Jewish ancestry - whose babies are at higher risk - and be made available to others.
But by this spring, evidence had emerged that some doctors were misinterpreting results, leading to unnecessary prenatal tests that increased chances of miscarriage.
Now, a Johns Hopkins University think tank has seized on the screening as a case study of the complexities society might face as the number of genetic tests explodes in coming years. At a center symposium last week, Kathy Hudson, director of the university's Genetics and Public Policy Center in Washington, called the cystic fibrosis tests "the first example of widespread genetic reproductive screening."
"You're making your decisions about really dramatic - and possibly traumatic - interventions based solely on ... a genetic test, and it's really important it be right," Hudson said in an interview, noting that such screening is often offered to couples who are expecting, allowing them to prepare for a sick child or to terminate the pregnancy.
Though predictive tests for genetic diseases have been administered to prospective parents for decades - including for sickle cell anemia in African-Americans and Tay-Sachs in Ashkenazi Jews - experts say the cystic fibrosis test is the first widely used reproductive screening to rely on DNA variations. Most of the tests are regulated as laboratory services, not products, meaning they don't require Food and Drug Administration approval in advance.
At the symposium last week, participants debated the merits of more regulation, which the FDA said it is considering.
Among the issues raised by the tests:
Guidelines backed by the American College of Medical Genetics and the American College of Obstetricians and Gynecologists call for screening that detects 25 of the more than 900 known mutations of the gene associated with cystic fibrosis, excluding changes that are rare or don't cause classic CF. That means someone who tests negative still could have the gene and could have a child with cystic fibrosis if her sexual partner also is a carrier of the mutated gene.
Even if both parents are carriers, there is only a 25 percent chance their child will have cystic fibrosis, a disease of the body's mucus glands that affects about 30,000 Americans and causes life-shortening digestion and breathing problems.
Some mutations must occur in tandem for cystic fibrosis to result. A variant known as 5T is common but contributes to classic cystic fibrosis only when it appears in combination with another mutation of the gene. But many doctors are ordering prenatal tests for the disease after finding only the 5T variant in one or both parents, according to a study by laboratory operator Quest Diagnostics Inc.
"Especially with genetic tests, we're going to learn as we go along, and we're going to encounter things we didn't anticipate," said Dr. Deborah Driscoll, a University of Pennsylvania geneticist. "But there are certainly problems."
In a March presentation, American College of Medical Genetics Executive Director Michael S. Watson warned 500 doctors that misinterpreted screening results had led some couples to terminate pregnancies.
But Watson said last week in an interview that his information was "anecdotal," and he had no evidence that abortions resulted. And no miscarriages or abortions resulted from doctors' confusion about test results in cases Quest studied, said Dr. Charles Strom, director of the company's genetic testing center.
Dr. Heather Stanley-Christian, a clinical geneticist and director of maternal-fetal medicine at Franklin Square Hospital Center, said she follows the guidelines in offering the tests. She said she prefers that obstetricians and general practitioners involve a geneticist in interpreting, and helping couples cope with, the results.
"I think cystic fibrosis screening is just beginning to be recognized as an important screening policy," she said. "Unfortunately, it does add another level of anxiety to the parents: It's just another thing to worry about."