The Downside of Precision Medicine: Tragic Cardiac Death Led to 20 Misdiagnoses

Genetic testing has its benefits, but there are potential dangers when used incorrectly.

This warning was highlighted after the sudden death of a 13-year-old boy that resulted in more than 20 of his relatives receiving an incorrect diagnosis of QT syndrome.

According to a new study published in theMayo Clinic Proceedings, authors cautioned that this useful tool should be used carefully, and that results should be scrutinized and not taken as gospel.

“While the technological advances in genetic sequencing have been exponential, our ability to interpret the results has not kept pace,” said senior study author Michael J. Ackerman, MD, PhD.

QT syndrome is an inherited heart rhythm condition that can potentially cause rapid and chaotic heartbeat, which in some cases, can result in sudden cardiac death. Furthermore, individuals can be born with a genetic mutation that increases their risk of long QT syndrome.

Following the boy’s sudden death, his family members were diagnosed with this syndrome and his brother received animplantable cardioverter defibrillator. On the father’s side of the family, specific genetic testing was performed, which led to more than 20 family members misdiagnosed with long QT syndrome.

After the family sought out a second opinion at the Mayo Clinic, Ackerman was skeptical of the diagnosis. That’s because 40% of patients diagnosed with QT syndrome who went to the Mayo Clinic ended up leaving without the diagnosis, with a majority reclassified as normal.

“The family’s case appeared to be another case of mistaken identity with wrong conclusions being rendered to the data ascertained, especially the genetic test results,” Ackerman said. “In fact, none of the relatives who sought a second opinion at Mayo Clinic had personal symptoms of long QT syndrome, and none exhibited any electrocardiographic evidence of long QT syndrome at rest or with treadmill stress testing.”

Unfortunately these mistaken identities have resulted in the boy’s brother receiving 2 inappropriate shocks since given the defibrillator.

To figure out what the real cause of the boy’s death was, researchers used the molecular autopsy.

“We discovered that the boy died tragically from an abnormal heart muscle condition caused by an entirely different genetic defect — unrelated to long QT syndrome – that was confined to only the sudden death victim,” Ackerman said.

The study’s findings indicated the importance of using genetic testing correctly, because of the harm it can cause.

“This family study highlights just how important it is to get things right on the first attempt, as it takes a tremendous amount of time, energy, and money to reverse course and do it over again,” Ackerman said. “It also depicts exactly the wrong way of using genetic testing and also precisely the right way of using and interpreting genetic testing. Ultimately, the clinician clinician’s long-standing role to meticulously phenotype (characterize) his or her patient and his or her family is what matters most. When the pursuit of the genotype gets in front of the establishment of the phenotype, bad things happen.”