Minor Operations

Genetic testing for children and adolescents presents complex ethical issues.

By Laura Beil featured image Illustration by Jasu Hu

As a teenager, Christal Shiller joined the softball team at her high school in Columbus, Ohio. Before long, she noticed she was remarkably out of shape: She couldn’t make a dash for first base or a running leap for a fly ball without gasping for breath.

That she had been born with cardiac problems didn’t occur to her, even though her mother had died when Shiller was 8 years old. When she reached young adulthood and it became clear that her problem was more than just lack of physical fitness, Shiller received a diagnosis of restrictive cardiomyopathy, a condition that causes the heart muscle to thicken, constricting blood flow. The disease had no doubt taken Shiller’s mother at age 31; one of her aunts died of the same condition at age 41.

In early 2016, when she was in her late 30s, Shiller underwent genetic testing to confirm suspicions that her heart problems were inherited. The test found a mutation in a gene that is crucial for healthy heart muscle. Patients can manage over time with medications, but there is no cure. Shiller received a heart transplant that same year.

But Shiller and her husband were left with a dilemma: whether to test their 8-year-old daughter for the same genetic condition that had struck her mother, grandmother, and aunt. “She has no symptoms. She runs, she plays, she does everything she wants to do,” Shiller says. “I did have one physician at one point tell us that her atrium looks slightly enlarged. But that could be normal for her.”

Even the usefulness of a positive test was unclear. “What’s it going to do to her life? Just because she has the gene doesn’t mean she would ever have symptoms of the disease,” Shiller says. “That was always in the back of our minds.” If she did in fact have the mutation, could anything slow the disease she would face as an adult? And would a positive test ruin her chances of getting health and life insurance as an adult?

Complex Ethics

These questions and others complicate the idea of genetic testing in children and adolescents, an issue that stands to become more prominent as scientists identify the genetic foundations for more diseases, while online companies continue to enter the market with direct-to-consumer tests for disease risk, diet advice, and even athletic ability. While any question of genetic testing comes with its own complicated set of ethics, children warrant special considerations because the decisions to test are often made for them and could affect the rest of their lives.

“If it’s actionable — if there is something you can do — then a genetic test would be appropriate for a child. But that’s a pretty short list,” says Timothy Caulfield, a professor of health law and policy at the University of Alberta’s Health Law Institute. “Something you test for needs to be for the good of the child. That’s a dominant theme in this area — the interest of the child should be the main concern.”

In that vein, there is widespread agreement among experts that children should be tested for genetic conditions when such information could help them medically, either with a treatment given immediately, or, if possible, one that delays the condition as a child ages.

“What’s it going to do to her life? Just because she has the gene doesn’t mean she would ever have symptoms of the disease.”

That’s why every year about 4 million American newborns are tested for metabolic, hematologic, and endocrine conditions that lend themselves to early intervention. (Examples include sickle cell disease and cystic fibrosis.) Tests are also warranted if a child shows symptoms of a disease that has a specific treatment. And that list may grow as research progresses. In fall 2017, the government approved a gene therapy to correct a form of blindness that starts in childhood.

Genetic testing becomes controversial when the disease course is less certain. For instance, against expert advice, several states have passed laws allowing routine screening for Krabbe disease, a rare disorder of nerve fibers in which babies gradually lose their sight, hearing, and ability to swallow. Most die young. But beyond a bone marrow transplant performed in the first weeks of life — a difficult procedure — there’s no way to prevent the disease. And not all infants who test positive will develop symptoms in childhood. In this case, “some states are screening for conditions not recommended for inclusion in a universal, state-mandated newborn screening program,” says Lainie Ross, a pediatrician and a professor at the University of Chicago. When there’s no clear therapy that needs to start in childhood, she says tests should wait. She believes the Krabbe screening program is not ready for prime time, and when it is included on state screening panels, parents should have the right to refuse.

Experts also agree that minors shouldn’t be tested for diseases like Alzheimer’s, Huntington’s, or even breast cancer, which wouldn’t appear for decades. After all, most at-risk adults for Huntington’s choose not to be tested. In 1995, the American Society for Human Genetics (ASHG) issued guidelines with that conclusion, a viewpoint reaffirmed in 2015. Unless there is some kind of action to be taken in childhood, testing for adult-onset conditions should be deferred “at least until the child is an older adolescent who can participate in decision-making in a relatively mature manner,” the guidelines say. (The American Academy of Pediatrics and the American College of Medical Genetics and Genomics issued a statement in 2013 that also argued against testing adolescents, except in rare circumstances.)

The main alteration ASHG made to the original 1995 guidelines was to allow slightly more wiggle room, depending on the circumstances. “I think the interpretation [of the 1995 guidelines] was, ‘Don’t do this,’ ” says Jeffrey Botkin, the head of medical ethics at the University of Utah School of Medicine and the lead author of the revised ASHG guidelines. “It was taken to such an extent that folks weren’t even doing research.”

Not all parents agree with expert guidelines. The idea of testing only for treatable conditions doesn’t account for the fact that medical science is constantly moving forward, and that genetic information might keep parents engaged in research, says Matt Might, the director of the Hugh Kaul Personalized Medicine Institute at the University of Alabama at Birmingham School of Medicine. Online and in print, Might has chronicled how he and his wife have struggled to find the genetic cause of their son’s severe and unexplained symptoms that appeared shortly after birth. Their son was finally diagnosed with a rare, previously unknown genetic condition: His body cannot make a key enzyme.

“Originally there was nothing for him, since he was the first patient,” Might says, “but that’s changed in just five years. There are treatments in development right now that seem to help.” The Mights also tested their daughter, born after their son, for the condition. She was neither affected nor a carrier, but her tests helped solve her brother’s mystery. “I have a real problem with doctors making ethical determinations on behalf of parents,” says Might.

Direct-to-Consumer Testing

Outside the doctor’s office, genetic testing becomes even more problematic for “lifestyle” genetics, whose value is unclear. Companies such as DNAFit, Athletigen, and Soccer Genomics say they allow consumers to tailor diet and exercise to their genes. (For more on this topic, see “Elite Athletes” in Genome’s Summer 2016 issue.) The company 23andMe offers tests that might predict the future risk of 10 diseases, including celiac disease. The products are usually marketed to adults, but some parents choose to make testing a family affair. However, professional guidelines from the American Academy of Pediatrics and the American College of Medical Genetics and Genomics “strongly discourage the use of direct-to-consumer and home kit genetic testing of children because of the lack of oversight on test content, accuracy, and interpretation,” a view also held by ASHG.

“I have a real problem with doctors making ethical determinations on behalf of parents.”

While he agrees with this position, Michael White, a geneticist at the Washington University School of Medicine in St. Louis, says that disease-risk testing may become more widespread as the price continues to fall and the tests get more comprehensive. “There’s this vision that everybody is going to have these tests done, and it’s going to be part of your medical record,” he says. Because the information seems mostly benign — conveying risk but not actual illness — many parents figure ‘why not,’ ” White says. “The main argument for not testing is that you want to preserve the child’s autonomy to make the decision herself whether to have the information.”

Tests for athletic ability, which have no medical value, are among the most controversial. In 2015, the University of Alberta’s Caulfield and his colleagues noted in the Journal of Law and the Biosciences that while these tests are sold to adults, in the hyper-competitive arena of youth sports,“there seems a real possibility that some parents will want to maximize their child’s odds at achieving athletic success through genetic testing.” The fear, Caulfield says, is that parents will use results to steer their sons and daughters into or away from a particular sport at a time when too little is known about what the results mean.

He sent off for one. “I’ve been a sprinter my whole life,” Caulfield says. “I was the fastest kid in the class. I met my wife on a track team. I ran track in university. I really defined myself as a sprinter. But I get my genetic tests back, and they say ‘Unlikely Sprinter.’ Had I gotten that test when I was 6, my whole life might have played out differently.”

What the Kids Think

While the adults work this issue out, scientists are still evaluating how children feel about the issue. One review published in 2016 in Genetics in Medicine was reassuring, finding that among 13 studies that examined the psychological processing of genetic information, there was little evidence of harm, though the review cautioned that long-term research was still lacking.

Nonetheless, minors, especially older children and adolescents, want to be involved in discussions of genetic testing, says Alanna Kulchak Rahm, an assistant professor in the Genomic Medicine Institute at Geisinger in Pennsylvania. She had long wanted to explore how adolescents felt about the recommendation against genetic screening for adult-onset diseases. In 2016, she was alerted to the annual DNA Day essay contest for ASHG, which was asking just that question. “This dropped out of the sky,” Rahm says. “It was a nice convenience sample, asking exactly the question we wanted to know [the answer to].”

Last October at ASHG’s annual meeting, Rahm presented the analysis of the 1,241 high school teenagers who wrote essays explaining their positions on testing children for adult disease. The teenagers were divided over whether testing should be deferred for adult conditions in general. But whether the condition had a treatment made a difference: for non-preventable conditions like Huntington’s and Alzheimer’s, about 60 percent agreed that deferring testing is a good idea, but for conditions like breast cancer risk, which have medical treatment, most disagreed with the guidelines to defer testing until adulthood.

What struck Rahm most was the sophistication of the answers. “Kids really can think through this,” she says. “They want a voice in this conversation.”

As for the Shillers, they wrestled with the question of whether to test their daughter for over a year. They felt uncomfortable making a decision that she might want to make herself when she got older. Then she began to show worrisome signs — the shallow breathing that Shiller remembered from her own childhood. In 2017, when their daughter was 9, the Shillers finally had her tested. “You make decisions for your child your whole life,” she says.

Her daughter’s results came back positive for the mutation. While not the result her parents had hoped for, they are glad to have an answer. Even though there is no cure, Shiller says, “now that we know, we can maybe do some things ahead of time. We’re asking, ‘What can we do now that may help her later?’ ”