Saturday, February 4, 2006
SIDS kills about 2,500 babies each year. Blacks have a higher risk of being diagnosed.
Researchers have identified a genetic variation that increases by 24 times the risk of a black baby in the United States succumbing to sudden infant death syndrome, or crib death.
According to a report published last week in the Journal of Clinical Investigation, about one in nine American blacks carries a copy of the variant gene, but children who carry two copies of the mutation face the increased risk.
Overall, mutations in the gene, called SCN5A, were found in 5 percent of the 133 SIDS cases in black infants reviewed by scientists. And the researchers estimate that half of the deaths resulted from the specific variant that increases a baby's risk of developing an abnormal heart rhythm when put under stress.
While the variant alone "does not cause SIDS, our findings suggest that it renders infants vulnerable to environmental challenges, such as long pauses in respiration, that are tolerated in children without the mutation," said Dr. Steven Goldstein, professor and chairman of pediatrics at the University of Chicago and director of the study. His team also included scientists at Yale University, Howard University and Ohio State University.
Focus of research
Goldstein's research has focused on understanding the role of ion channels, which control the electrical activity of nerves and muscles, in a variety of diseases, including dangerous heart rhythms and SIDS.
'The hope is that findings like this may one day allow us to intervene," Goldstein added. "We might screen to identify children at high risk and teach parents how to lessen the likelihood of secondary challenges. We have already begun to evaluate drugs that may mitigate the risk."
SIDS is the leading cause of infant death in the United States, claiming some 2,500 babies each year, or a third of all deaths between 1 month and 1 year of age. Blacks have three times the risk of SIDS than do Caucasians and six times the risk than Hispanics or Asians. This has prompted many researchers to look for genetic causes for the syndrome.
Researchers in a separate program at Rush University Medical Center in Chicago have reported finding in babies who died of SIDS a number of mutations in genes linked to the regulation of breathing. In a 2004 study, they identified 11 different protein-changing mutations. Of the 15 percent of the 92 SIDS babies who had one of the mutations, 71 percent were black.
For the new report, Goldstein's team compared genes in tissue collected from 133 black infants in the United States with a diagnosis of SIDS after autopsy with samples from 1,056 black adults with no known health problems.
What researchers found
The researchers found that in 3 out of the 133 SIDS cases, or 2.3 percent, the babies had two copies of the genetic variant of SCN5A, compared to just one individual in the control group. Four other SIDS cases had damaging mutations to one copy.
When the scientists first looked at how the mutation affected electrical signals in cells, they found no difference between cells with the variant and normal genes. But when they simulated the environment in which an infant has frequent spells in interrupted breathing, or apnea, the cells coded for abnormal signals began to misbehave, setting the stage for abnormal heart rhythms.
Jonathan Makielski from the University of Wisconsin, commenting on the new study in a separate article in the journal, observed that a number of genetic abnormalities regulating both breathing and now heart rhythm, coupled with environmental factors, will eventually be found to contribute to the risk of SIDS.
Goldstein's team also found that treating cells that carried two copies of the new mutation with the drug mexiletine, used in adults with heart arrhythmias, was able to restore normal function in the cells even when breathing interruption was simulated.
But the researchers stressed that while the drug might turn out to be a preventive strategy, their findings must be replicated and the risks and benefits of treatment studied before genetic screening should be considered even for infants considered to be at higher risk for SIDS.