As Testing Grows, So Do Questions About Its Scope
On a rainy day in May, 46 people had their blood drawn in the basement of the Park Avenue Synagogue on the Upper East Side of Manhattan as part of a community screening for Jewish genetic diseases.
Blood samples from the young married couples and individuals in committed relationships were then shipped off to diagnostic laboratories, where they were tested for 16 recessive diseases that occur at higher frequencies among Ashkenazi Jews than in the population at large.
Each of the participants could have decided not to test for any of the 16 diseases, yet every single person opted for the full battery.
“We just wanted to do the whole thing,” said Doron Scher, 25, an accountant from Manhattan’s Upper West Side who attended the screening with his wife, Cheryl.
“I always like more information,” added Aaron Herman, 32, a consultant from the Upper West Side who got tested with his wife, Tani Schwartz-Herman. “It’s very helpful to know your options.”
The responses of these and other attendees of the screening event are pretty typical, experts say. In a study published in the November 2010 issue of the journal Human Mutation, researchers from the Mount Sinai School of Medicine found that more than 95% of Ashkenazi Jewish men and women who underwent screening in the New York metropolitan area between 2008 and 2009 chose to include all available disorders. Pointing to those results, the authors concluded that the Jewish community “is strongly in favor of including all 16 disorders.”
Nicole Schreiber-Agus, scientific director of the Yeshiva University Program for Jewish Genetic Health, which sponsored the screening, also backs that conclusion. “Screenees are opting for more-is-better,” she said.
But some experts take exception to this interpretation of people’s attitudes toward testing. They note that few people who participate in such community screenings have the information they need to make informed decisions about whether to be tested for all the diseases.
In fact, most participants do not really differentiate between all the diseases, which vary from potentially mild to deadly and have vastly different rates of occurrence.
“Even though there’s a huge clinical spectrum, they’re all lumped as the same thing,” said Benjamin Wilfond, director of the Treuman Katz Center for Pediatric Bioethics at Seattle Children’s Hospital. “And there’s very little opportunity for people to ask, ‘Should I care about these things differently?’”
At brief genetic counseling sessions at the May event, only Gaucher disease, an enzyme deficiency disorder, was singled out from among the genetic pack. Although some forms of the disease can be quite debilitating, experts have suggested that more than half of Ashkenazi Jews who carry two copies of the most common mutation for Gaucher have such minimal symptoms that these individuals never come to medical attention. Indeed, some people first learn through community screening that they are affected.
The fact that other diseases are not life threatening, or that some can be managed with drugs, was not routinely mentioned by genetic counselors.
For example, Usher syndrome can cause both deafness and blindness, but many prospective parents consider those symptoms manageable enough that they would still proceed with having a child despite the risks that he or she could be affected with the condition. As such, if more people knew that two types of Usher are included in routine community screening, some might choose to opt out of those genetic tests since they wouldn’t act on that information anyway.
Dr. Susan Klugman, director of clinical services and community outreach for the Yeshiva University Program for Jewish Genetic Health and an organizer of the May screening, notes that information about each disease was provided in the reading material given to each attendee. Participants also had the opportunity to ask questions.
But, Klugman said, the event was “advertised as a screen for 16 [diseases], and people signed up to it knowing this.” Besides, she added, “We have found people want as much information as possible and as much information as is available to them.”
The amount of information available — and packaged together — is rapidly increasing. Ten years ago, screenings included no more than four major diseases. Five years ago, nine diseases was the upper limit. Now, some screens include 19 diseases, and counting.
The number of diseases tested has “snowballed,” said Dr. Joel Charrow, a medical geneticist at Children’s Memorial Hospital in Chicago and an adviser to the Victor Center for the Prevention of Jewish Genetic Diseases, a leading reproductive screening institute based at the Albert Einstein Healthcare Network in Philadelphia.
Charrow questioned whether more thought or medical discussion should go into adding additional diseases to the routine battery of tests. “I don’t think it has been a rational process or one that’s been based on any epidemiologically or genetically sound principles,” he said.
The most recent disease added to many screenings is Walker-Warburg syndrome, a form of muscular dystrophy associated with brain and eye abnormalities that affects around 1 in 90,000 children in the Jewish community. In April, the Victor Center added Walker-Warburg to its recommended panel, bringing the tally up to 19. In June, the Chicago Center for Jewish Genetic Disorders similarly expanded its testing panel to 19 disorders, up from 9.
Defenders of testing for Walker-Warburg highlight the severity of the condition. “Having seen families who have children with this disease, I can tell you it’s universally fatal” in early infancy, said Dr. Wendy Chung, assistant professor of pediatrics at Columbia University Medical Center.
Critics note, however, that Walker-Warburg syndrome and other uncommon diseases on the larger testing panels are extremely rare. And given the low probability of two disease carriers meeting and raising a family, Dr. John Mitchell, director of the carrier screening program at the Montreal Children’s Hospital, questions the utility and cost-effectiveness of blanket screening Jewish parents-to-be for these types of disorders. Like other recessive diseases tested, both parents would have to be carriers of the gene carrying the disease for their children to have a risk of contracting it.
“Once you get up to some of the rare diseases, you have to question why you’re offering the testing and what difference it makes to some of those individuals,” he said.
Testing for more diseases, he noted, can raise people’s anxiety with little added benefit. It may also deter some couples from trying to start a family. Plus, investing time and money to test for rarer conditions can take limited resources away from testing more people for the more common diseases although the cost is coming down (see “Higher Tech Lowers Cost of Genetic Screening,” page 20).
An alternative approach to extremely rare diseases would be to only screen prospective parents with documented family histories of such conditions.
“You could prevent 80% to 90% of all cases by doing extended family testing, instead of mass-population screening” for rare conditions such as Walker-Warburg, where the carrier rate is less than 1 in 100, said Dr. Michael Kaback, a clinical geneticist at the University of California, San Diego School of Medicine, who organized the first screening programs for Tay-Sachs carriers in the 1970s.
But Rabbi Peter Kasdan, an adviser to the nonprofit Jewish Genetic Disease Consortium, defends the practice of testing for as many Jewish genetic diseases as possible, regardless of their frequency or severity. For decades he hasn’t officiated a wedding unless both newlyweds have been genetically tested.
“These things are not added lightly,” Kasdan said. “I’m not going to distinguish between Tay-Sachs and Canavan, or even Walker-Warburg. If it affects Jewish people of Ashkenazi descent, they ought to know about it, and they ought to get tested for it.”
Dr. Jodi Hoffman, director of the Victor Outreach and Screening Program for Ashkenazi Jewish Genetic Diseases at Tufts Medical Center, says that testing for more diseases empowers prospective parents of Ashkenazi heritage to make informed reproductive decisions. And even learning about some of the less severe ailments can be helpful, she argues.
“There are a lot of benefits to finding out early, even if your choice isn’t to prevent bringing a child into the world,” Hoffman said, “but it’s the chance to diagnose and treat a child early after birth.”
Contact Elie Dolgin at email@example.com