Defects in gene called RyR2 cause malfunctions in the heart's electrical system

May 2 2005

Mayo Clinic researchers have identified defects in a second gene called RyR2 that causes malfunctions in the heart's electrical system and contributes to what were previously unexplained drownings.

Mayo researchers first discovered defects in a gene that causes the heart's electrical system to malfunction and described how it might cause a drowning of an otherwise healthy person and reported their findings in a study published in the New England Journal of Medicine in 1999. The newest findings are described in the current issue of Mayo Clinic Proceedings.

In the newest study, Mayo researchers conducted sleuthlike molecular autopsies or postmortem genetic testing on coroners' cases of unexplained and unexpected drownings that were referred to the Sudden Death Genomics Laboratory at Mayo Clinic in Rochester, Minn.

"Harnessing the power from the Human Genome Project, our research team has solved these inexplicable tragedies through direct genetic evidence," says Michael Ackerman, M.D., Ph.D., director of the Sudden Death Genomics Laboratory at Mayo Clinic in Rochester. "Swimming and genetic glitches in the heart's electrical system appear to be a bad combination, but we need further study to understand why and how this occurs."

In the Mayo Clinic Proceedings article, two cases were studied by Mayo Clinic researchers in which both individuals were proficient swimmers. A teenage girl died at swim team practice, after being found floating facedown in the swimming pool. She had just finished swimming four laps. Efforts to resuscitate her were unsuccessful. Another case involved a young boy who failed to surface immediately after diving in the water at a lake. Efforts to resuscitate him also were unsuccessful.

Akin to the investigators on the television show Crime Scene Investigation, senior research technologist David Tester is one of Dr. Ackerman's lead sudden death investigators who cracked the code and pinpointed the critical misspelling in the 3 billion base pair genetic code for these drowning victims.

There are approximately 3,000 to 4,000 drowning accidents per year in the United States, and it's estimated four to six times that many near-drowning incidents, says Dr. Ackerman. The near-drowning accidents contribute to a number of cases where the individuals experience significant brain damage because of the time without oxygen. Most events are explained. For instance, many can be attributed to children being unsupervised, poor swimming ability, alcohol or other drugs or seizures. However, an appreciable number are unexplained.

"On land, if you suffer from one of these genetic glitches that causes your heart to spin electrically out of control and you faint, you might wake up with bruises, but if this occurs in water, even if the heart regains control quickly, it may be too late; you've probably drowned," says Dr. Ackerman. "With defects in this gene and the previous gene, swimming becomes a potentially dangerous situation."

The mutations or genetic glitches in RyR2 are undetectable with a regular electrocardiogram (EKG or ECG). The heart rhythm condition resulting from such genetic glitches is called catecholaminergic polymorphic ventricular tachycardia or CPVT and was first described only 10 years ago. Physicians should consider CPVT in the setting of a suspicious faint during exercise or an unexplained drowning or a family history of early sudden deaths where all standard tests are normal, says Dr. Ackerman. CPVT can only be exposed if the suspicion for it is high and the person is run through an exercise or adrenaline stress test.

With respect to summer fun, swimming, and the tragedy of a drowning, Dr. Ackerman urges CSI-like tenacity and scrutiny when a drowning or near-drowning occurs that just does not make sense.

"We estimate that 10 to 20 percent of these kind of drownings are from genetic glitches in the heart's electrical system," says Dr. Ackerman. "Now we need to prove if that estimate is correct."

To do so, Dr. Ackerman and colleagues are working to establish a national registry of unexplained drownings so systematic sudden death investigations (SDI) can be conducted.