Babies at risk

The genetics of sudden infant death syndrome

Melissa Marino, Ph.D.
Published: October, 2007

Fatal arrhythmias could be the underlying culprits in some cases of sudden infant death syndrome (SIDS). A pair of studies in the Jan. 23, 2007 Circulation reported that nearly 10 percent of SIDS victims have mutations or variations in genes associated with potentially lethal heart rhythms.

SIDS is the leading cause of death in infants aged 1 month to 1 year in the United States, according to the Centers for Disease Control and Prevention.

The number of SIDS deaths has been declining since the early 1990s—likely due to educational campaigns about the risk of putting infants to sleep on their stomachs and exposing them to cigarette smoke. But despite the drop, SIDS continues to be a leading cause of infant mortality in developed countries, and the underlying basis of the condition remains unclear.

A popular theory proposes that SIDS occurs because of a combination of risks including abnormal physiological state, environmental factors and developmental vulnerabilities. Genetic factors may also be important.

“SIDS is not one disease,” says Alfred L. George Jr., M.D., director of the Division of Genetic Medicine at Vanderbilt. “Multiple conditions can increase the risk of sudden death in an infant. Some have been identified, but many have not.”

Anecdotal evidence previously suggested that some SIDS victims carry mutations in genes associated with conditions such as the long QT syndrome that predispose individuals to life-threatening arrhythmias and sudden death. But the proportion of SIDS cases that carry such mutations was not clear.

George’s collaborators, Peter Schwartz, M.D., in Italy, and Torleiv Rognum, M.D., Ph.D., in Norway, led the efforts to screen seven arrhythmia-associated genes in 201 SIDS cases from Norway—the largest ever genetic survey of a SIDS cohort. The results published in Circulation showed that 9.5 percent of SIDS victims harbored mutations in genes associated with inherited forms of cardiac arrhythmia, such as long QT syndrome.

The researchers identified mutations in several genes, including the gene that encodes the cardiac sodium channel—a protein that regulates the electrical properties of heart cells. George’s lab then performed studies to understand the physiological consequences of mutations in the cardiac sodium channel gene, called SCN5A, which has previously been associated with long QT syndrome and several other conditions that cause unstable heart rhythms and sudden death.

“We observed a pattern of SCN5A dysfunction that is reminiscent of what’s been observed in long QT syndrome,” George says. “That gives us confidence that the mutations observed in SIDS victims are not benign genetic variants—but rather could increase the risk of potentially lethal arrhythmias.”

The researchers have similar evidence, to be published separately, demonstrating that mutations in heart potassium channels are also contributing factors in SIDS.

The findings also suggest that there may be strategies to identify whether infants carry one of these mutations before the tragic event of their death, George says.

“We are not recommending that a population-wide genetic screening be done, but there may be simpler, cost-effective measures that should be investigated further, perhaps performing ECG (electrocardiogram) screening of infants, although this idea is controversial.”

Inherited arrhythmias are manageable conditions that can be treated with medications or implantable devices, George says.

“There’s potentially an infant death every other day in the U.S. due to this problem (arrhythmias),” he says. “Exactly how best to identify this risk and prevent arrhythmia-related death during infancy needs to be determined.”

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