Every year in the United States, hundreds of children die for undetermined reasons, usually while sleeping or at rest. Because of the way deaths are investigated and certified, it is difficult to say how often this happens. According to some estimates, several hundred children between the ages of 1 and 18 die suddenly of unexplained causes each year.
When the child is less than 12 months old, it is called sudden infant death syndrome (SIDS). According to the CDC, 1,250 such deaths qualified in 2019, about three times the number of sudden unexplained deaths in children (SUDC).
SIDS causes three times as many deaths as SUDC, but receives 20 times more research funding.
Laura Gould has been working for decades to change that. After losing her 15-month-old child in 1997, she co-founded the SUDC Registry and Research Collaborative (SUDCRRC) with a neurologist at New York University.
By using the database to compare 124 molecular autopsy results with the parents’ genetic data, the researchers have now revealed a potential cause for some cases of SUDC.
In nearly a dozen cases, the researchers identified eight genetic variants linked to epilepsy, cardiac arrhythmias and neurodevelopmental disorders.
Six of the genetic variants are known to be involved in calcium signalling, which allows the heart muscle to contract and neurons to trigger messages.
In most cases, the parents of the deceased children did not show the same mutations, which means that they were not inherited but derived at random.
According to the researchers, it is unlikely that a parent would have two children with the same lethal variant.
“Our study is the largest of its kind to date, the first to prove that there are specific genetic causes of SUDC, and the first to complete any part of the risk picture,” says NYU neuroscientist Richard Tsien.
“In addition to providing comfort to parents, new findings about the genetic changes involved will accumulate over time, reveal the mechanisms responsible and serve as the basis for new treatment approaches.”
The study specifically looked for 137 genetic variants linked to heart problems and epilepsy, as this appears to be the cause of most cases of SUDC.
Compared to the general population, these variants were ten times more likely to occur among SUDC cases.
But there are probably other explanations out there. The genetic variants identified in the present study were found in only 9% of the cohort; more work needs to be done to understand what causes the majority of SUDC cases.
A second study, conducted by the same team of researchers, took the data further. This time they looked for 294 potentially lethal genetic variants in 352 cases of SUDC.
Among a subset of 73 cases, where parental data were also available, the authors found 37 genetic variants that are likely to be linked to neurological, cardiac or systemic diseases.
The researchers note that the presence of pathogenic gene variants “does not in itself establish causality”, but their findings are a very promising start not only to provide better diagnosis and peace of mind to bereaved parents, but also to potentially identify risk factors that lead to SUDC before tragedy strikes.
“In addition to providing comfort to parents, further discoveries about the genetic changes involved will accumulate over time, revealing the mechanisms responsible.