In 2004, a seemingly healthy 12-year-old died while running around outside. Months later, the same thing happened to the child's 10-year-old sibling. Within a few years, two more children from the same family — part of an Amish community in the Eastern United States — would meet the same mysterious fate. "Autopsies didn't offer any clues," CNN reports. "The children's hearts appeared normal. The family had what they referred to as 'the curse of sudden death.' And medical examiners couldn't figure out why."
Across the country, Michael Ackerman, M.D., Ph.D., and his colleagues began working to answer that question. Dr. Ackerman, a genetic cardiologist and director of the Windland Smith Rice Sudden Death Genomics Laboratory at Mayo Clinic, had been part of the team that "pioneered the concept of molecular autopsy, using genetic testing to understand the cause of death in sudden unexplained cases," CNN reports. A medical examiner had reached out to Dr. Ackerman to see if his lab could determine what had caused the Amish siblings' deaths. "The team suspected that a gene called RYR2 could be the culprit," according to CNN, because "mutations of the gene can cause a cardiac arrhythmic disorder that can lead to exercise-fainting spells, seizures or even sudden cardiac death. But when they analyzed the gene to check for mutations, nothing turned up."
Meanwhile, more children from Amish families were dying sudden, unexplained deaths — 18 children in all. Doctors and genetic counselors from around the country reached out to Dr. Ackerman with their stories and sent DNA samples to his lab for analysis. Still, he and his colleagues could not crack the case. "We were stuck," Dr. Ackerman tells the Rochester Post-Bulletin.
But they didn't consider that a permanent condition. "We are tenacious, and we never give up," Dr. Ackerman tells the publication. As new technology for gene sequencing developed, the team took another look at the case. "We sort of regrouped and said let's try again with the new technology," he says.
The new view provided an answer. Just as the team had originally suspected, the problem lay in the RYR2 gene. "But there wasn't just one mistake in the gene," CNN reports. "More than 300,000 base pairs in the gene had been duplicated." The condition is a recessive disorder, which means children must "inherit a mutated gene from each parent" to develop it, according to CNN. If both parents are carriers, there's a 25 percent chance they'll pass the disorder on to their children. The Amish community "may be more vulnerable to recessive inherited conditions because they are descended from a small number of ancestors and tend to intermarry," CNN reports. Genetic testing can now identify carriers, and that information can help people "make informed decisions about whether or not they should marry another person who is also a carrier," according to CNN.
For now, the only treatment available to those with the mutation is to have an implantable cardioverter-defibrillator placed in their chest to detect and correct abnormal heart rhythms. But Dr. Ackerman and his colleagues are working to find a medication to treat the condition, which would be less invasive and less expensive than an implanted device. "We're kind of racing against the clock," he tells CNN. "We need to get this figured out as fast as we can."
You can learn more about the discovery in JAMA Cardiology. Then leave a comment below before using the handy social media tools atop this page to share this story with others.