Availability of prenatal genetic tests questioned

Screening for every condition not practical solution

As researchers discover more genetic links to diseases, newer and more accurate diagnostic and screening tests are making their way to the market.

But with an increasing array of tests out there, it is becoming more difficult for providers to determine which screening and diagnostic tests will offer tangible benefits to patients and which will most likely cost them and their insurers vast amounts of money and raise more questions than answers.

A recent article in The New York Times profiled several new parents who were upset that existing genetic screening tests, which might have indicated their offspring would be at risk for certain medical conditions, were never performed.

The article pointed out that some tests are routinely offered to screen for conditions that are rarely seen, whereas tests that could detect more common conditions are not routinely given.

The articles failed to point out, however, that genetic screening tests are not simple, black-and-white, positive vs. negative indicators, notes Dawn Allain, MS, CGC, a genetic counselor with Waukesha Memorial Hospital in Waukesha, WI, and president of the Wallingford, PA-based National Society of Genetic Counselors.

"Genetic testing is not that straightforward," she explains. "It is not a matter of coming in and getting some standardized test that is the same for everyone that will say, Yes, you will have this’, or, No, you won’t.’ And we want to make sure that results interpretation for individuals will be able to actually provide them with appropriate medical management."

One of the examples cited in the newspaper article highlighted the recommendation from the American College of Obstetricians and Gynecologists that all prospective parents be screened to determine whether they are genetic carriers of cystic fibrosis (CF). But, the article states, the incidence of CF in the U.S. population is much lower than that of mental retardation, which often is caused by another genetic problem known as Fragile X syndrome.

Why are most prospective parents screened for CF, while the screening for Fragile X usually is recommended only for those with a family history of mental retardation?

The answer is complicated, Allain says. And the genetic screening test to detect mutations in the genes causing development of cystic fibrosis is much more sensitive than the currently available test for Fragile X.

"The CF test is more accurate," she says. "We can say with certainty that if a child is born with a certain mutation, [he or she] will have CF. And we can predict, very reliably, the risks that two parents who are carriers of the genetic mutations will have an affected child."

The gene mutations linked to other diseases are often more complex. Some diseases may be caused by more than one gene mutation, and some are caused by mutations in different genes. Without a family history, a clinician looking at someone’s raw DNA profile will not know what to look for.

While a test is available that indicates risk of Fragile X, that test is not as accurate or predictive. Given in patients with no family history of mental retardation, the results would not have much meaning.

Most genetic screening that is available now is designed to be informative only in the context of a detailed family history of disease, known in the field as a pedigree.

"It is not as simple as getting a blood test and then getting a yes/no answer," Allain says. "In no way are we near that level of care at this point in genetic services. Family history is going to be the biggest tool that a health care provider and genetic counselor will utilize to ascertain the appropriate application of genetic testing of an individual — as well as looking at ethnicity, with regards to carrier testing for sickle cell disease, cystic fibrosis, Canavan’s, and those kinds of things."

Cost and potential benefit also are concerns

Clinicians also have to weigh other practical factors when determining whether to recommend a certain screening test, adds Haynes Robinson, MD, director of the Genetic Center at Children’s Hospital Medical Center in Akron, OH.

Many of the genetic conditions that can be screened for are extremely rare, and the tests often are very costly.

"That has been the subject of much debate, lately. I think there is a point of practicality," Robinson says. "You try to mold your testing patterns to what is reasonable. It is not yet reasonable to test for everything that is out there. Even if it were reasonable, at least today, no one could afford it — only a very, very small percentage of people. We are talking about screenings that may cost $5,000 for one test."

An example given in The New York Times’ article was a woman whose son was born with hereditary deafness, which, in European and most American populations, is most often caused by a mutation in the gene connexin 26. A test is available for this mutation, but is rarely offered.

All people have two copies of this gene. When two parents each have a flawed, recessive copy of the gene, their baby may be born with hearing loss. But since that gene is recessive, the condition is very rare. Some studies have indicated its occurrence may be higher among Ashkenazi Jews and people of Asian descent. However, without a family history indicating a risk, or some other factor, Robinson says he does not recommend routine screening for that mutation.

"I don’t offer it to every patient I see," he says. "I don’t offer it to patients unless it is in their pedigree, and it is not going to be in most people’s pedigree because most of these are recessive disorders."

Currently, there are 200-300 conditions that might be detected through a genetic screen, but at thousands of dollars per test and, without any indication that the patient is particularly at risk, payers are not likely to cover the cost.

"It would cost a fortune to do every test for everyone, at this point," Robinson says. "Even then, you are talking about catching one case out of possibly thousands of people."

Physicians also must weigh the potential for benefit from early detection vs. the cost of the test, Robinson adds. If the test indicates that two parents’ offspring is at higher risk of a certain condition, does knowing that risk help improve the resulting infant’s condition? Are there ways to prevent the development of the condition at all?

"That’s the operating principle behind newborn screening," Robinson continues. "One: you want to prevent the condition if possible. Two: if you can’t prevent it, you want to ameliorate it."

As an example, he points to the now-common test performed on newborns to detect phenylketonuria (PKU), a metabolic disorder that prevents a person from processing the essential amino acid phenylalanine. Before the test was available, this condition often was not detected in time to prevent the accumulation of toxic levels of the amino acid in the person’s system, resulting in mental retardation. Now a simple blood test performed within a few hours of birth can detect the condition and allow treatment to begin to prevent the condition.

In a similar way, the earlier a child — who was born without the ability to hear — is given appropriate treatment and support, the better able he or she will be to cope with the condition.

"I think the difference is also in the availability of intervention," agrees Allain. "I think Fragile X is an example. It is a devastating diagnosis to get. It is going to be devastating in any family to find out your child has a genetic disorder. The difference between doing carrier screening for CF is, if it is detected, then we know that there is a risk, and when the child is born with the disorder we can start medical intervention right away. That is not to say that [early intervention strategies for] a child with mental retardation would not be appropriate; but with CF, it is life-dependent, and with Fragile X, it is life-skill and learning potential that would be affected.

"There are hard issues to balance, which makes deciding which tests to offer even more difficult from a societal perspective," she continues.

The science of genetic screening is changing almost day-to-day, notes Robinson, and, in a few years, more comprehensive screening may be available in a practical way that will make more widespread screening easier.

"You have probably read about micro-array technology. People are going in that direction now," he notes. "They are attempting to look at the entire genome, but that is fraught with all kinds of problems, too. Because, as they do that, and look genetic alterations along the path of our genome, they will see some alterations that are benign and don’t cause a problem. It takes time to determine which are significant and which are not."

One panel currently in development would allow clinicians to look for approximately 30 different conditions at one time, with one test, Robinson says. However, even those 30 are just a drop in the bucket of the many gene-linked conditions that exist.

"There are another 200-300 tests that aren’t even part of that," Robinson notes. "It is a question of practicality. All of these disorders are rare. When you talk about the disorders you screen for, even for newborn screening, you are talking about one in 50,000 or one case in 20,000, so that is the problem with genetic disorders. Virtually, all of them are individually rare, but collectively they are enormous." 


1. Harmon A. As gene test menu grows, who gets to choose? The New York Times, July 21, 2004:A1.


  • Dawn Allain, National Society of Genetic Counselors, Executive Office, 233 Canterbury Drive, Wallingford, PA 19086-6617.
  • Haynes Robinson, Akron Children’s Hospital, One Perkins Square, Akron, OH 44308.