Results of a Long QT Syndrome study in the current issue of Circulation play an important role in understanding genetic testing's role in diagnosing disease, according to the senior author, Michael Ackerman, M.D., Ph.D., the Mayo Clinic pediatric cardiologist who directs Mayo's Long QT Syndrome Clinic and is the director of the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory.
LQTS is a disorder of the electrical system of the heart and affects 1 in 2,500 people.
In the multi-center study that involved Dr. Arthur Wilde in the Netherlands and scientists from PGxHealth, genetic testing results of nearly 400 "slam dunk" LQTS patients and nearly 1,400 healthy volunteers showed that there is a background noise rate of rare variants present in about 4 percent of healthy Caucasian volunteers and that mutation type and mutation location are critical determinants to distinguish this background noise from true LQTS-causative mutations, Dr. Ackerman says.
"Our research shows that genetic testing is just one piece of the information a physician needs to look at," he says. The results demonstrate that genetic testing does not give a "yes or no" answer for LQTS or other diseases, and it means that physicians need to meticulously interpret this particular diagnostic test with the same scrutiny and tenacity as any other diagnostic test, such as the electrocardiogram (ECG). "It's proving what we've long know in genetic testing circles -- that these are not binary tests but are probabilistic tests whereby some test results are going to provide 'no-doubt-about-it' diease mutations. Whereas other test results may report a mutation whose pathogenicity is uncertain."
The Circulation paper is another critical piece in the maturation of LQTS genetic testing from discovery, translation, implementation and now post-implementation interpretation, Dr. Ackerman says. First clinically described in 1957, it took until 1995 until the first genes were discovered. In 2004, the first clinically available test for LQTS became available in North America.
In LQTS, approximately 5 percent to 10 percent of the time, its first symptom is sudden death, often related to physical exertion or auditory triggers such as an alarm clock. However, most cases can be diagnosed following warning signs (sudden, without warning, fainting spells or concerning family history) that suggest its potential presence and from objective data derived from an electrocardiogram (ECG), exercise or adrenalin stress testing, and genetic testing.
Mayo Clinic and Dr. Ackerman have a financial interest in LQTS technology. This technology has been licensed to a commercial entity and both Mayo Clinic and Dr. Ackerman receive royalties from that license.