Stethoscope on base pairs graphOur ability to interpret genetic test results does not always keep pace with technological advances. This is according to a new study from the Mayo Clinic, which found that 20 members of the same family had been misdiagnosed after “inappropriate use of genetic testing and incorrect interpretation of genetic test results.”

The case was prompted by the sudden death of a 13-year-old boy, who was subsequently diagnosed with long QT syndrome, an inherited heart rhythm condition that can cause the heartbeat to become fast and chaotic. After his death, 20 members of the boy’s family were also diagnosed with long QT, and his brother even had a device surgically implanted designed to prevent fatal arrhythmias from happening.

However, suspicion was aroused when the family presented to the Mayo Clinic’s Windland Smith Rice Sudden Death Genomics Laboratory for a second opinion. “Specific genetic testing was performed throughout the father’s side of the family, leading to the eventual, but incorrect, diagnosis of long QT syndrome in more than 20 family members,” explained laboratory director Michael J Ackerman.

“This 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,” he says. “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.”

In fact, since receiving the implantable cardioverter-defibrillator, the boy’s brother has had two inappropriate shocks delivered.

Michael Ackerman and his colleagues managed to pin down the actual cause of the boy’s death using a “whole-exome molecular autopsy coupled with genomic triangulation”. 

“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,” he explained.

“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. 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.”