Article published in Statens Serum Institut News, original research published in Brain
A large-scale case-control study implicates genes critical for fever response and genes for communication between nerve cells.
It is usually an unexpected and frightening experience for parents when their child has a febrile seizure. Occurring in 3-5% of infants febrile seizures are the most common type of abnormal brain activity during childhood. While most febrile seizures are benign and self-limiting with no recurrence, about 7% of children with febrile seizures will later develop epilepsy.
Now, a new international genetic study led by researchers from Statens Serum Institut (SSI) in Copenhagen and conducted in collaboration with other research groups in Denmark and Australia have identified seven novel regions of the genome linked to febrile seizures in the largest case-control study reported for this common childhood disorder.
The research has just been published in the leading international neurological journal Brain.
Genes related to fever response
The researchers analyzed variants in the DNA of 7,635 children from Denmark and Australia, who had experienced one or more episodes of febrile seizures. They also analyzed a control group of 83,966 children without febrile seizures.
Almost 7 million genetic variants were interrogated and the study identified seven new gene regions robustly linked to increased risk of developing febrile seizures. The study also confirmed four previously known genetic associations for febrile seizures established by the same team in 2014.
Two of the new regions contained genes of major importance in the development of fevers in mammals. For one gene, called PTGER3, the mechanism has been elucidated in mouse experiments. When this gene was silenced in a specific brain region called the median preoptic nucleus, the mice were unable to develop fevers. Another gene called IL10 encodes a signaling molecule that normally functions to suppress fevers.
Dr. Bjarke Feenstra, a senior researcher and group leader at Statens Serum Institut in Denmark, who was the lead author of the study, said: “The connections to fever response are intriguing. We hypothesize that genetic changes that affect the way the PTGER3 and IL10 genes function may lead to a more pronounced fever response, which in turn could increase the susceptibility of children to febrile seizures”.