Gene mutations linked to heart disease have been thought to be a leading cause of Sudden Infant Death Syndrome, but a new study from Mayo Clinic, UK and Danish researchers finds they are responsible for far fewer deaths from SIDS than previously thought. The findings open up new avenues of investigation into the possible causes of the syndrome and may help prevent unnecessary genetic testing of surviving family members. The results of the study appear in the Journal of the American College of Cardiology.
The research, considered the largest genetic investigation into SIDS, found that genetic mutations associated with heart disease account for around 5% of deaths from SIDS. In the study, whole-exome sequencing and targeted analysis of 90 genes implicated in heart disease were applied to 419 unrelated SIDS cases.
Previous smaller studies involving up to 170 cases have suggested that heart disease-related genetic mutations cause up to 20% of SIDS deaths.
SIDS is the sudden and unexpected death of an infant less than one year old that remains unexplained despite extensive clinical and pathological investigations. SIDS accounts for up to 80% of all sudden unexpected infant deaths, with an incidence of 0.4 in 1,000 live births in the UK and 0.5 in 1,000 live births in the US.
The peak incidence occurs between 2 months and 4 months of age; the average age of infants in the new study was 2.7 months. The syndrome is more common in boys.
“Thanks to this research, we now know that the vast majority of SIDS cases do not stem from genetic heart disease,” says co-lead author Michael Ackerman, MD, Ph.D., director of Long QT Syndrome/Rhythm genetic heart from the Mayo Clinic. Windland Smith Rice Sudden Death Clinic and Genomics Laboratory. “We are now turning our attention to genes involved in other organ systems, such as the brain, to determine their potential contribution. Additionally, we are now exploring other genetic contributions to SIDS, as it is now abundantly clear that most cases of SIDS are not due to a single genetic cause.”
In 2001, Dr. Ackerman and his colleagues at Mayo discovered genetic mutations causing long QT syndrome, a heart disease, in a small number of SIDS cases derived from the first population-based study of the syndrome. Long QT is an inherited heart rhythm disorder that can cause rapid, bumpy heartbeats. Although estimates suggest that LQTS occurs in only 1 in 2,000 people, it is a common cause of sudden cardiac death before the age of 40.
Now, 17 years later, researchers have analyzed every gene implicated in sudden cardiac death due to genetic abnormalities in heart muscle and rhythm, says Dr. Ackerman.
“Our findings also underscore the critical importance of accurate variant classification to enable appropriate counseling of surviving family members,” says Dr. Ackerman.
The mislabeling or premature labeling of a genetic variant as a pathogen has the potential to harm patients and their families.”