Since the boy's autopsy report seemingly failed to explain his death, more than 20 of his relatives underwent genetic testing for heart conditions that could put them at increased risk of the same fate. The tests diagnosed the family members, including the boy's brother, as having a potentially deadly genetic heart rhythm condition called long QT syndrome
As a result, a heart defibrillator was surgically implanted in the brother's chest to prevent any potentially fatal heart rhythms, or arrhythmias.
Then the family asked Ackerman for a second opinion about their diagnoses and overall health. Ackerman was skeptical of the previous diagnoses, he said. And after evaluating the family members, he soon concluded that they did not have long QT syndrome after all.
"At one level, families like this one go through intense frustration and anger about the missteps that were made. At another level, there is confirmation with their own gut instinct that things were not hanging all together," said Ackerman, a genetic cardiologist and director of the Windland Smith Rice Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minnesota.
When Ackerman and his colleagues realized that a genetic evaluation of the deceased boy was never performed, they conducted tests and discovered that the boy didn't have long QT syndrome, either.
"Instead, the boy actually died a sudden death from a genetically mediated heart muscle disease due to a completely different mutation that was present in him and him alone," Ackerman said.
A paper about the boy's case, which occurred over the past five years, was published in the journal Mayo Clinic Proceedings
on Monday. The family referenced in the paper has requested to remain anonymous.
In the paper, the researchers called for a more careful use of genetic testing tools
and a more careful interpretation of genetic test results.
"Right now, the evaluation of sudden death victims throughout this country is very heterogeneous, and the evaluation of their surviving relatives is even more variable. Tread with caution," Ackerman said.
"The medical community and community at large need to get a better grasp on genetic testing and precision medicine rather than just using them as buzzwords. When used properly, these tests are incredibly helpful," he said. "But we must become wiser users of genetic testing and even wiser interpreters of the genetic test results so that we can make wise conclusions."
The first mistake made in the family's initial diagnosis was that the 13-year-old was never tested, Ackerman said. The second was that the test results for long QT syndrome were accepted as accurate even though the family members showed no clinical signs of the disease.
For the paper, the researchers collected DNA from the boy and conducted a molecular autopsy, in which DNA was isolated and sequenced in a way that allowed genetic variants to be re-examined and analyzed.
The potential for disparities
The findings in the paper are a cautionary and constructive story about the risks associated with genetic testing, said Dr. Arthur Caplan, a professor and founding head of the division of bioethics at New York University Langone Medical Center in New York.
"We haven't really figured out the significances of all the genetic mutations that are found and what they mean in different environments, meaning the same mutation in a different person may not mean the same disease," Caplan said.
For instance, "whether the mutations that are found mean the same thing in other ethnic groups, we're not sure," he said.
People of African ancestry have greater genetic diversity than people of European ancestry, which could lead to a greater risk for misdiagnoses. A study published in the New England Journal of Medicine
in August found this to be the case in genetic testing for the heart disease hypertrophic cardiomyopathy.
The condition, in which the heart muscle becomes abnormally thick, has been associated with a number of athletes suddenly collapsing
on the field or court.
"Because we don't yet have a large enough sample of patients from a number of different ethnicities -- and also we don't have, for some of the diseases, enough samples period to compare these cases -- there is a chance of some of these misdiagnoses," said Dr. Isaac Kohane, professor of biomedical informatics at Harvard University and lead author of the New England Journal of Medicine study.
Additionally, in some cases your environment and lifestyle can play just as large of a role in your health as your genes, Kohane pointed out.
"Even diseases that we used to think of as being purely genetic are ending up having an environmental component," he said.
Kohane called the new Mayo Clinic paper "a very credible chronology that I am sure has happened in many different diseases. And it's happening today, and many people are generally unaware."
Finding solace in testing
Nonetheless, there is still a place in medicine for genetic testing, which can have positive outcomes such as helping patients make informed decisions about managing their health care.
A negative test result could eliminate the need for unnecessary checkups or screening tests, according to the National Institutes of Health
A positive test result could allow patients to take preventive measures in their health care, like actress Angelina Jolie
did. She revealed last year that she had her breasts and ovaries removed to prevent cancer.
Jolie noted in a New York Times op-ed that she lost her mother, aunt and grandmother to cancer. Her mother was diagnosed with ovarian cancer
at age 49.
However, as the Mayo Clinic paper shows, genetic testing is still complex.
"Unless you have a family history, I wouldn't be so worried about that," Caplan said of genetic testing.
"What I would be more worried about is, can I lose weight? Can I exercise? Can I not drink too much? Can I not abuse prescription drugs? Can I wear a helmet when I ride my bike?" he said. "In other words, while we're all fascinated by genes ... it's still the case that the major health care risks, unless you have a family history of something, don't require a genetic test."