Vancouver, BC - A molecular genetic autopsy performed on the tissue of a 21-year-old woman who died suddenly of unexplained causes identified a novel mutation in the KCNH2 gene at a region that is known to give rise to long-QT syndrome [1]. This novel molecular autopsy identification of a hidden cause of sudden cardiac death was presented in a poster here at the Canadian Cardiovascular Congress 2006.

Dr Michael Gollob (University of Ottawa Heart Institute, ON) told heartwire that sudden cardiac death in an otherwise healthy individual is always a tragedy, and in up to 40% of cases, routine autopsy fails to identify a specific pathologic diagnosis. He added that it is very likely, however, that a significant proportion of these young victims die from a genetic arrhythmia—that is, from a purely electrical disease of the heart in which there is no associated structural disease for pathologists to view.

In this case, a 21-year-old woman was found dead in her bed some hours after studying for university exams. She had been taking a "cold medicine" for upper-respiratory-tract symptoms, and she had a previous history of recurrent syncope with no specific etiology. A standard autopsy revealed a myxomatous mitral valve and "septum at origin of left main coronary." Her mother had a previous diagnosis of "epilepsy" that was based on frequent episodes of passing out and observed seizurelike activity.

Gollob explained that following genetic counseling, the woman's parents consented to genetic analysis of tissue from their daughter. Genomic DNA was extracted from liver tissue using standard techniques and was analyzed for genetic mutations in genes that are known to cause sudden cardiac death: genes known to give rise to the long-QT syndrome, Brugada syndrome, or catecholaminergic polymorphic ventricular tachycardia.

Direct DNA sequencing identified a novel mutation in the HERG gene, otherwise known as KCNH2, at a "mutation hot spot" region of the gene that is known to give rise to long-QT syndrome.

In an ongoing process, the researchers assessed surviving family members to see whether they were carriers for this genetic mutation. They were able to reassure the woman's surviving sister that she does not carry this genetic mutation and is not at risk for long-QT syndrome. The victim's mother, however, had an inappropriate diagnosis of epilepsy. She actually had long-QT syndrome and carried the same genetic mutation as her deceased daughter. The mother is now being appropriately treated. "We have in our experience seven cases of young individuals who were diagnosed with epilepsy but who actually had long-QT syndrome," Gollob added.

Genetic testing might prevent similar tragedies

"We propose that genetic testing should be part of the standard autopsy in autopsy-negative sudden cardiac death in previously healthy young individuals," said Gollob. "We feel this is important, because not only will it provide closure to the family and to the community, it also provides an opportunity to definitively screen surviving family members to see whether they also harbor the same genetic disease and are at risk of sudden death."