The sudden and unexpected death of a child is a tragedy made all the worse when there's absolutely no explanation.
Each year in the United States, hundreds of children die for undetermined reasons, usually in their sleep or while resting. Due to the way deaths are investigated and certified, it's hard to say how often this occurs. By some estimates, several hundred children aged between 1 and 18 die suddenly from unexplained causes each year.
When the child is younger than 12 months, it's known as sudden infant death syndrome (SIDS). According to the CDC, 1,250 such deaths qualified in 2019 – roughly three times the number of sudden unexplained deaths in children (SUDC).
SIDS causes three times as many deaths as SUDC, yet receives 20 times the amount of research funding.
Laura Gould has been working for decades to change that. After losing her 15-month-year old in 1997, she co-founded the SUDC Registry and Research Collaborative (SUDCRRC) with a neurologist from New York University.
Using the database to compare 124 molecular autopsy results with genetic data from the parents, researchers have now revealed a potential cause for some instances of SUDC.
In nearly a dozen cases, researchers identified eight gene variants linked to epilepsy, heart arrhythmias, and neurodevelopmental disorders.
Six of the gene variants are known to be involved in calcium signaling, which is what allows the heart muscle to contract and neurons to fire off messages.
In most cases, the parents of the deceased children did not show the same mutations, which means they were not passed down but randomly derived.
The chance of a parent having two children with the same deadly variant is unlikely, the researchers say.
"Our study is the largest of its kind to date, the first to prove that there are definite genetic causes of SUDC, and the first to fill in any portion of the risk picture," says neuroscientist Richard Tsien from NYU.
"Along with providing comfort to parents, new findings about genetic changes involved will accumulate with time, reveal the mechanisms responsible, and serve as the basis for new treatment approaches."
The study looked specifically for 137 genetic variants that are linked to cardiac and epilepsy issues, as this seems to be what causes most cases of SUDC.
Compared to the general population, these variants were ten times more likely to show up among cases of SUDC.
But there are likely other explanations out there. The genetic variants identified in the current study were only found in 9 percent of the cohort; more work will need to be done to figure out what causes the majority of SUDC cases.
A second study, conducted by the same team of researchers, dug into the data further. This time, they were looking for 294 potentially deadly genetic variants in 352 SUDC cases.
Among a subset of 73 cases, where parental data were also available, the authors found 37 gene variants that are likely related 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 highly promising start for not only providing better diagnosis and peace of mind for bereaved parents, but potentially identifying risk factors that lead to SUDC before tragedy strikes.
"Along with providing comfort to parents, new findings about genetic changes involved will accumulate with time, reveal the mechanisms responsible, and serve as the basis for new treatment approaches," says Tsien.
The first study was published in Proceedings of the National Academy of Sciences; the second study was published in Genetics in Medicine.