US researchers have identified a gene mutation linked to a 24-fold increased risk of sudden infant death syndrome (SIDS), or 'cot death', in African Americans. The team, based at the University of Chicago, says the altered form of the SCN5A gene makes infants vulnerable to 'environmental challenges' such as interrupted breathing. The study, published in the Journal of Clinical Investigation, could eventually lead to screening to identify infants at high risk of SIDS, say the scientists.
SIDS causes around 2,500 unexplained infant deaths in the US every year. African Americans have a three-fold higher risk than people of European origin, and six times the risk of Hispanic or Asian Americans. Research into possible genetic causes of SIDS has looked at genes involved in controlling the electrical activity of nerves and muscles. The SCN5A gene makes a protein that controls the flow of sodium ions in and out of cells - a process which, if disrupted in heart cells, can increase the risk of abnormal heart rhythms.
The scientists studied tissue samples from 133 deceased African American infants, who had been diagnosed with SIDS at autopsy, and compared them with samples from 1,056 healthy African American adults. They found that five per cent of the SIDS cases had mutations in the SCN5A gene. One specific gene change, known as Y1103, is known to confer an eight-fold increased risk of heart arrhythmia in African-American adults who inherit one copy of the mutation. Three of the SIDS cases (2.3 per cent) had inherited two copies of this mutation, one from each parent, compared to only one of the controls (0.1 per cent).
The scientists think that the gene change makes infants susceptible to temporary pauses in breathing, which can be tolerated by children without the mutation. The faulty SCN5A protein appears to malfunction when in a slightly acidic environment, such as that found in muscle cells deprived of oxygen. However, treating the cells with a drug called mexiletine - used to treat heart arrhythmias in adults - can make the protein work properly again, even in oxygen-starved cells.
The team stress that further research is necessary to confirm the link between SIDS and the SCN5A gene. But if confirmed, they say the work suggests that genetic tests could be used to screen high-risk infants, such as those with siblings who have died from SIDS. It also shows that mexiletine could be used as a possible preventative treatment for such babies. Jonathan Makielski, of the University of Wisconsin, commented that a number of genetic abnormalities regulating both breathing and heart rhythm, coupled with other factors, will eventually be found to increase the risk of SIDS.