To Know or Not to Know? The Genetic Testing Decision

Lori Erby could hear hesitation, uncertainty, even fear enter the woman’s voice as she recalled the moment she learned that her husband’s genetic test was positive. There was no longer any doubt that he had a hereditary form of amyotrophic lateral sclerosis (ALS), the neurodegenerative disease for which there is no cure.

Although the wife said she had agreed to receive the test results so that she could be the one to deliver the news, the couple had not discussed the ramifications of that decision with a genetic counselor. Now the conversation was occurring for the first time, long distance. And the wife was in a quandary about what she should tell her husband.

“She was very concerned that the results would strip her husband of hope,” says Erby, a genetic counselor in the neuromuscular disease clinic at Johns Hopkins Hospital. “She considered just letting him believe that the results were inconclusive, but what would that mean for their children and his other relatives? They would also be affected by these results. They were now at risk for a condition that none of them had considered, and they might have as much as a 90 percent chance of developing symptoms by age 70. Shouldn’t they have the opportunity to know that?

“It was a big dilemma—and a pretty good example of how complicated this kind of knowledge, and counseling, can get.”

Erby, 37, is among roughly 30 genetic counselors working in labs, clinics, and units across Johns Hopkins Hospital and its affiliate Kennedy Krieger Institute. They are charged with helping to interpret and explain patients’ biological blueprints, a topic that grows more complex every day as scientists try to make sense of the dizzying volume of genomic information.

With genetic tests now available for more than 2,500 diseases, there is an increasing demand for prenatal testing, for tests to find the basis for children’s undiagnosed developmental disabilities, and for tests to gauge the likelihood of acquiring certain inherited cancers, cardiac conditions, and Alzheimer’s disease.

In addition, a growing number of people without any symptoms of a disease, or even a family history of it, are asking what their genes say about potential health risks. Some choose to speak with traditionally trained genetic counselors, others send bio-samples directly to consumer testing companies, and some “citizen scientists” pool their genetic information in DIY groups in order to pursue their own research into a variety of conditions.

Meanwhile, researchers, institutional review boards, and bioethicists throughout the world are scrambling to keep pace with what some consider the “Wild West” landscape of genetic information sharing.

Genetic counselors, who are trained to understand and communicate all aspects of such testing, have become more vital than ever, observers say, and will play an “enormous role” in shaping the future of personalized medicine, according to Dave Kaufman, director of research and statistics for the Genetics and Public Policy Center of the Johns Hopkins Berman Institute of Bioethics.

“Most clinicians haven’t thought much about how to deliver this kind of information and neither have most genetic researchers,” he says. “As we go forward, we need to integrate the methods that genetic counselors are using into how we return results.”

The world of genetic counseling is young—the National Society of Genetic Counselors only dates back to 1979—and small, with about 3,000 trained professionals in the United States. More than half work in prenatal and cancer counseling, according to an NSGC survey taken last year, and 36 percent are employed in university medical centers. Another 34 percent work in both public and private hospitals and medical centers while many of the remaining counselors are found in commercial and academic diagnostic laboratories, biotechnology companies, and government agencies.

At Hopkins, a core group of counselors housed in the McKusick-Nathans Institute of Genetic Medicine works with clients in a general genetics clinic and also with patients in neurology and ophthalmology. Others provide full-time services in adult oncology and cardiology and maternal/fetal medicine. One counselor works in the DNA diagnostics lab, representing the genetic counseling viewpoint while fielding physician questions and requests.

Genetic counselors tend to enter the required master’s degree program from backgrounds in science, nursing, teaching, and social work. “A lot of us are searching for this perfect mix of science and people, of personal interactions,” says Rebecca Nagy, NSGC president, who works primarily with cancer patients at the Ohio State University Comprehensive Cancer Center.

Since 1996, Hopkins’ Bloomberg School of Public Health has run a genetic counseling degree program at Hopkins with the National Human Genome Research Institute of the National Institutes of Health. The curriculum focuses on genetics technology, counseling, and communications skills while also emphasizing research into the field and its methods.

“I think we’re all shocked at how fast the world of genetics is changing,” says Carolyn Applegate, a genetic counselor at the Institute of Genetic Medicine who works with a variety of patients as well as with the families of children who have chromosomal abnormalities, intellectual disabilities, autism, and other conditions. She’s found that new technological tools are speeding the process for those embarked on the long, frustrating genetics quest known as “the diagnostic odyssey.”

“There are more issues to talk through than ever before,” says Applegate. “Traditionally we were testing one gene at a time. Now we’re doing whole-exome testing that looks across all the protein coding parts of genes at once to see if we can find a change that would explain an individual’s condition.”

Indeed, diagnosing the cause of an inherited disease used to mean cataloging a patient’s signs and symptoms, making an educated guess as to what gene might be at fault, and testing specifically for it. If that gene proved negative for a mutation, it was time to test another. In recent years, however, it has become not only faster but also more cost-effective to analyze a bigger picture. Sometimes the search uncovers more than expected and presents different issues for the adults and children who are being tested.

“Meeting with the parents of a young child who might have whole exome sequencing is challenging because there is so much to discuss in order for them to make a truly informed decision about testing,” explains Amanda Bergner, another genetic counselor at the Institute of Genetic Medicine.

“By doing whole exome sequencing to look for the cause of a 2-year-old’s seizures, for instance, we can learn that she carries a genetic mutation that gives her an 80 percent chance of developing breast cancer in her lifetime. How does the family cope with this information? How do they share it with their child, and when? Is insurance coverage for this child affected now or in the future because of this test result? Does this type of testing infringe on the rights of the child to be part of the decision-making process around learning about her own health risks? There is precedent in the genetics community for not testing minors unless there is a clear medical benefit prior to the age of majority.”

As the use of this technology becomes more widespread it is provoking many such conversations, Bergner notes. Meanwhile, whole exome sequencing can also turn up genetic irregularities of unknown significance.

“Interpretation is a huge issue right now,” Rebecca Nagy says. “Each one of us has a lot of genomic variation and much of it doesn’t mean a thing. So how do we figure out what is ‘noise’ and what is truly something that might put you at higher risk for certain diseases? Another big challenge is how to effectively consent a patient to anticipate all the things we might encounter, as well as some of those things that we don’t even know yet.”

Such issues can be overlooked when genetic tests are ordered. “Genetic counselors are trained not only to review inheritance patterns and statistical risks of passing a gene to a future child, but also how to support patients and their families as they consider the complicated social, emotional, and psychological responses to receiving genetic information,” Bergner says.

Genetic counselors meet with a client before testing to take personal and family history and to discuss the possible consequences of the test. (See sidebar.) In that meeting, they also agree on how the client wants to receive the news—by phone or in person, for instance—and whether the client wants the counselor to meet with family members and relatives.

Ada Hamosh, a physician and researcher in the Institute of Genetic Medicine, says genetic counselors are the best trained to guide patients through testing—a journey that covers practical as well as emotional terrain.

“You need to understand what tests will and won’t yield, and what results you want back,” says Hamosh. “For example: As someone who’s in perfect health, are you sure you want the test now when this disease doesn’t have any effective treatments? If so, why? Will your insurance pay for the pre-symptomatic test? If the results are positive, do you already have stable health insurance? What about life insurance? You should think about getting that before you’re diagnosed.”

The cost of testing a single gene ranges roughly from $1,500 to $3,400 she says. In the future, when many predict that the cost of sequencing an individual’s entire genome will drop to $1,000, Hamosh envisions that the demand for detailed interpretation may increase dramatically along with the need for prior counseling.

Gail Geller, a professor in the Department of Medicine and the Berman Institute of Bioethics, studies how clinicians and patients communicate and make decisions under conditions of uncertainty. She says research studies suggest that the majority of people want to know all that can be known about their genome. But a significant minority only want to know about a condition if it is treatable. “There are plenty of people—and I’m among them—who say, ‘Why would I want to know my Alzheimer’s risk if there’s nothing I can do about it?’” Geller says.

The question “To know or not to know?” is polarizing patients/consumers who want to possess all available information about their own biological destinies and physicians/researchers who worry what they may do with it. Will someone with only a slightly elevated risk of breast cancer go ahead with a double mastectomy? Could someone abort a fetus over a result that’s misunderstood?

While Geller opposes restricting access to testing, she strongly recommends that consumers receive counseling prior to it. Like many of her colleagues, she worries that the field cannot meet the demand for its services without more graduate programs and alternative training for primary care physicians and other clinicians. (In the Genes to Society curriculum at the Johns Hopkins University School of Medicine, students study the subject of inherited disease at several points during their four years but learn very little about counseling.)

There are 35 accredited graduate programs in the United States and Canada that offer a master’s degree in genetic counseling, but many contain only six to 10 students per cohort. The program usually takes two years to complete.

Compensation may also be slowing growth: The average salary is $68,000 a year, according to the NSGC survey. Nagy expects that will increase if genetic counselors can bill for their services in the same way that physical therapists and audiologists do. “I think that advances in genomic technology are going to force things a bit and make advances happen sooner for us,” she says.

Some genetic counselors savor their roles as teachers, educating patients about the genetic testing and the science behind it. Others, like Erby, are drawn primarily to helping patients and their families frame and work through life-changing decisions.

She attends a peer supervision group for genetic counselors that meets regularly at the home of one of the members. The genetic counselors take turns describing difficult cases, seeking advice about how they might be more effective, and gaining support for their own emotional struggles with work.

Often, they don’t know how the story turns out for those they’ve counseled, and the uncertainty can prove haunting. So far, for instance, Erby has not received a follow-up call from the woman who was wrestling with telling her husband that he had ALS.

She also recalls counseling a young woman who was afraid she had inherited the neuromuscular condition that killed her father. Although the woman did not show any signs of the disease—symptoms do not usually appear until the late 40s or even 50s—she couldn’t wait much longer to decide whether to have children.

“Since her father and other affected family members were deceased, there was no one in the family for whom genetic testing would be completely informative,” Erby says. “But we knew from her family history that she was definitely at 50 percent risk for inheriting this. Without knowing which gene was responsible for her father’s condition, we couldn’t tell her if she had it, and she was stuck about what to do.”

Should this woman forfeit her dream of having children? What were the chances she would pass on the condition? If she developed the disease, would her children have to endure the pain she felt when her own parent died?

Erby met several times with the woman and her partner to guide them through the science, risks, and various future scenarios. By the end of the last session, the couple was of different minds. While the woman was very ambivalent about having children, her partner was prepared to embrace the risk.

“I don’t know what she ultimately decided,” the counselor says. “That was three years ago, and I still think about her all the time.”


Tough Conversations

Genetic counselors are trained to speak to patients about possible consequences of genetic testing – some of them practical, some emotional, some life changing. This conversation, or series of conversations, is an important aspect of informed consent and of preparing patients for potential outcomes. To illustrate some of the issues that can arise as part of counseling, Johns Hopkins genetic counselor Amanda Bergner offers the following scenario:

A 25-year-old single woman whose mother and sister are breast cancer survivors seeks to find out if she carries the gene for breast cancer. Although she has no symptoms of the disease, a positive test could indicate that she has a very high lifetime risk of developing breast cancer and possibly other cancers.

Creating a Pedigree: With the patient’s help, the genetic counselor will create a pedigree, an all-inclusive family history of multiple generations that shows various conditions and any previous genetic testing. It can help identify the relationships within her family and indicate who might be impacted by information learned through testing. This discussion may also show some of the family’s social relationships and differing health care beliefs and practices, information that may help the patient decide how to share genetic news. In addition to constructing the pedigree, the counselor will collect the patient’s personal and family medical records.

Who Gets Tested First? Another important decision is determining who will get tested first for the breast cancer gene. Because testing a person who has been diagnosed with breast cancer is the best route to discovering a gene change within a family, the patient needs to ask her mother or sister to be tested. That step may depend on who can better afford it: The first person in a family to undergo testing will incur a larger expense than those tested afterward because that individual’s genes must be sequenced completely. Once a mutation is found, subsequent tests can be targeted to the specific part of the gene.

Considering Possible Consequences: The counselor will introduce a spectrum of consequences that may arise from testing so that the patient is fully able to consider her choice. Such considerations might include:

If a test is positive, does she already have health insurance? And life insurance? What is she prepared to tell others in her immediate and extended family about the results? Does she know that her male relatives may also carry and pass on the “breast cancer gene”? Does she know that this result will also greatly raise her risk of ovarian cancer? Has she considered if, and how, she will share this information with an intimate partner and how it might affect their relationship?

If a test is negative, does she realize that the result does not mean that she will be free of all cancers throughout her life? Or that it might mean that she may have a deadly mutation for breast cancer but that the available technology did not find it? That she might need to consider having another test in several years? —LS

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