Genes don’t stand alone: Genetic testing leads to incorrect diagnoses

Genetic testing provides physicians with more information to help make an accurate diagnosis. It is not a fool-proof way to ensure the diagnosis is never incorrect—as new research from Mayo Clinic shows.

The sudden death of a 13-year-old boy resulted in the incorrect diagnosis of 20 family members with a potentially lethal heart rhythm condition. The faulty diagnosis occurred as a result of inappropriate use of genetic testing and incorrect interpretation of the results, according to research published in Mayo Clinic Proceedings.

"While the technological advances in genetic sequencing have been exponential, our ability to interpret the results has not kept pace," Michael J. Ackerman, MD, genetic cardiologist and director of Mayo Clinic's Windland Smith Rice Sudden Death Genomics Laboratory, said in a statement.

After the boy’s death, a number of family members were diagnosed with QT syndrome, an inherited heart rhythm condition that can potentially cause fast and chaotic heartbeats and cardiac death. A genetic mutation is often responsible for the condition.

A botched interpretation of genetic testing results led to the boy’s brother receiving an implantable cardioverter defibrillator, which can stop a potentially fatal arrhythmia. The boy did not actually have QT Syndrome, and, as a result, two inappropriate shocks were delivered to his heart.

"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," 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."

Molecular autopsy—a procedure pioneered by Ackerman and his team—was used to find the real cause of the boy’s death.

"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.

Ackerman stresses that this case shows the importance of taking a meticulous patient history and focusing on phenotype—or patient interaction with the environment—instead of relying on genetics alone.