A potential genetic link in Sudden Infant Death Syndrome identified – sciencedaily

Rare genetic mutations associated with impaired respiratory muscles are more common in children who die from Sudden Infant Death Syndrome (also known as “sudden infant death syndrome”) than in healthy controls, suggesting a possible genetic element of the disease, according to a case-control study in the UK and US published in The Lancet.

Typically, these mutations are not found in controls or are very rare, and typically found in fewer than five in 100,000 people. However, the study found such mutations in four of the 278 children who died from the syndrome. of sudden infant death syndrome, against any of the 729 healthy controls.

The authors stress that more research will be needed to understand the link identified and whether drug treatments might be suitable. They also point out that it’s not the only cause of Sudden Infant Death Syndrome, and other things play a role as well.

Sudden infant death syndrome is the unexpected death of an apparently healthy child. It is the leading cause of post-neonatal death in high-income countries, but deaths are rare and the risk to a baby is low. Typically, it affects children aged 2 to 4 months and is responsible for 2,400 deaths each year in the United States and around 300 in the United Kingdom.

The cause of the disorder is unknown, but the inability of babies to regulate their breathing is considered an important factor. It is more common in male babies and those born prematurely. Getting babies to sleep on their backs and not sleeping in the same bed as a parent is known to reduce the risk.

The study examined the prevalence of mutations in the SCN4A gene, which codes for an important cell surface receptor (a sodium ion channel protein in skeletal muscle). Expression of this cellular receptor in respiratory muscles is low at birth and increases during the first two years of life.

Mutations in this gene are associated with a range of genetic neuromuscular disorders, such as myotonia, periodic paralysis, myopathy, and myasthenic syndrome, as well as potentially fatal pauses in breathing and vocal cord spasms that cause temporarily difficult breathing or speaking.

The study included two cohorts of children of European Caucasian descent who died from Sudden Infant Death Syndrome in the UK and US, including 278 children in total (84 from UK and 194 from US) . All of the deaths were unexplained after extensive post-mortem investigations. These were matched to 729 adults who had no history of cardiovascular, respiratory, or neurological disease.

Tissues from each group were used and their genes were analyzed to identify if they had a mutation in the SCN4A gene and to confirm if the mutations affected the cell surface receptor for which the gene codes.

While the study found general mutations in the SCN4A gene in six of the 284 infants who died and in nine of the 729 controls, mutations that disrupted the cell surface receptor were only found in four of the infants who died from the syndrome. sudden infant death syndrome. , and none of the controls.

The authors conclude that the disruptive variants are overrepresented in this group and may indicate a genetic component of Sudden Infant Death Syndrome.

The authors suggest that this may increase susceptibility to sudden infant death syndrome in some cases, as the cell receptor becomes more commonly used. During this time, the mutation could potentially leave these children with weaker respiratory muscles and, if an external stressor affects their breathing (such as tobacco smoke, an entanglement in bedding, minor illness, or respiratory obstruction), they may be less able to correct their breathing, cough or catch their breath in response.

They point out that the genetic mutation is probably not the only cause of death, however, and safe sleep measures for babies are still essential to ensure safety.

Additionally, since SCN4A variants are found in some adults with neuromuscular disease, it is evident that SCN4A mutations are not always fatal.

“Our study is the first to link a genetic cause of respiratory muscle weakness to Sudden Infant Death Syndrome, and suggests that genes controlling respiratory muscle function may be important in this disease. However, more research is needed. to confirm and fully understand this link, “says corresponding author, Professor Michael Hanna, MRC Center for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, UK. “While there are drug treatments available for children and adults with genetic neuromuscular disorders caused by mutations in the SCN4A gene, it is not clear whether these treatments would reduce the risk of Sudden Infant Death Syndrome, and Further research is essential before these results can become relevant for treatment. “

Co-author Dr Michael Ackerman, Mayo Clinic, USA, says: “This international UK-US collaborative study provides exciting new evidence for a possible link between sodium channel dysfunction respiratory muscles and SIDS; further research is needed to confirm these findings and assess any potential clinical relevance.

The authors note some limitations, including the fact that the study only included whites of European descent, and the results will need to be confirmed in other ethnicities. In addition, because information from children who died from Sudden Infant Death Syndrome was anonymized, other clinical data was limited and other family members could not be tested. Prospective studies will be needed to confirm the link between the mutation and Sudden Infant Death Syndrome.

In a related commentary, Dr Stephen Cannon, UCLA, USA, says: “Sudden Infant Death Syndrome (SIDS) remains a major cause of infant mortality, despite a steadily declining incidence since the 1990s. The reasons decline are debated, but it could be due to methodological reasons (for example, changes in ratios or advances in the diagnosis of specific diseases) or to a reduction in risks, such as an increase in supine position. back for infants, as advocated by the Back to Sleep campaign. causes of SIDS is needed to identify high-risk infants and to develop interventions and guidelines that will prevent SIDS for all infants… Overall, the evidence is convincing that SCN4A variants with disruption of function of channels are over-represented in SIDS. “

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