Sudden infant death syndrome – long considered to be an unexplained phenomenon in apparently healthy children under the age of 1 – may in some cases have a genetic basis, suggests a new study.
The study, published Wednesday in The Lancet, found that a genetic mutation affecting respiratory muscle function was associated with SIDS in a subset of cases.
The mutation causes dysfunction that may complicate infants appropriate Responding to hypoxemia or low oxygen levels in the blood, researchers said. It changes the shape of a "sodium channel" that maintains an electric current to stimulate muscle contraction.
"I think the evidence is pretty convincing that some cases of SIDS are caused by sodium channel mutations," Dr. Michael Hanna. Professor of Clinical Neurology at University College London and lead author of the study
"There must be a flaw, and what we're saying is that the sodium channel makes it vulnerable in some cases."  Sudden infant death refers to the unexpected and unexplained death of a seemingly healthy infant between one month and one year, often while the child is asleep. The syndrome causes nearly 2,400 child deaths each year in the United States and is the leading cause of death in this age group in high-income countries, according to the National Institutes of Health.
The phenomenon has long been known for sleeping posture, as when babies sleep on their stomachs, and secondhand passive smoking, says Hanna.
"There is a big campaign in America and in Europe called the 'Back to Sleep' campaign," he said. "Basically, putting a baby on your back instead of sleeping in the front reduces the incidence of those deaths by about 60%."
But this study would be among the first to show that dysfunction in skeletal muscle electrical activity could also be a contributing factor. Stephen Cannon, neurologist and professor of physiology at the David Geffen School of Medicine at the University of California, Los Angeles, who was not involved in the research. 19659002] "These are very compelling data," Cannon said. "In the previous four or five years, cases of muscle defects in (newborns) and young children have caused respiratory problems, so it was a logical consequence that this could progress to something like SIDS." 196590000] Researchers compared the genomes of 278 children in the United States and the United Kingdom who died of SIDS with 729 ethnically adjusted controls. They found that an extremely rare mutation in a gene called SCN4A was present in four of the 278 SIDS cases but none of the controls.
The SCN4A gene encodes a sodium channel responsible for maintaining the electrical current that stimulates skeletal muscle. like those who are responsible for breathing. A disruptive mutation in this gene would normally be expected in less than one in 100,000 people, according to Cannon.
"The likelihood of seeing four in a group of 300 is just astronomical – there will not be a coincidence," Cannon said. "The numbers are small, which is a challenge, but that happens in exceptionally rare diseases."
A mutation in the SCN4A gene has been linked to skeletal muscle disease in adults. These disorders are typically characterized by an inability to effectively stimulate or relax skeletal muscle, resulting in excessive muscle stiffness or muscle weakness.
The common genetic basis between these adult muscle diseases and some cases of SIDS may influence the screening and counseling of future parents with known skeletal muscle disorders, Cannon suggests.
"An interesting spin-off to this study is whether the few thousand people who have these inherited muscle diseases in the United States should be advised and whether we should change the recommendations for their should be cared for infants," he said.
However, Hanna warned that the mutation was only found in 1.4% of infants who died of SIDS, which means that the great majority of cases are still caused by a variety of other factors. "I think it's probably an important factor, but it's not a single factor," he said. "And what could be the extra factor could be one of those environmental triggers," such as smoke exposure.
As the study looks at just one ion channel, future research might investigate similar changes in other channels, says Hanna
"Probably the respiratory muscles have about a hundred different ion channels ultimately responsible for normal contraction and relaxation of the respiratory muscles We only looked at one channel because our hypothesis led us there, "said Hanna.
"The next step is to look at all other channels," he added. "That, of course, requires further research on all these other genes."
The study looked exclusively at children of European descent, so the results may not be generalizable to people from other ethnic backgrounds. For example, African Americans are known to have an increased risk of SIDS, possibly due to this genetic mutation, according to Cannon.
What this means for the future of SIDS prevention is unclear. But some drugs, including sodium channel blockers such as mexiletine, could play a future role in the treatment of infants with a higher risk of SIDS, Cannon said.
"There are already drugs that can inhibit or block sodium channels and could therefore be very beneficial to bring the patient beyond vulnerability," Cannon said.
"If you know it's in the family, you can also be more alert to surveillance or other preventive measures that have been used in SIDS and other cases – for example, the careful positioning of a baby's sleep," he added added.