Febrile convulsions in children due to gene mutations

Gene mutations responsible for febrile convulsions in infants

04/11/2014

Around two to four of all children worldwide get febrile convulsions at a young age. For parents, it is usually a shock when they see their offspring suddenly twitching all over. Researchers have now found a previously unknown cause for the most common form of epileptic seizures.

Previously unknown cause detected
The most common form of epileptic seizures is febrile convulsions. Around two to four percent of all children are affected worldwide. In Germany, there are about 100,000 children who are affected. Often they occur at the age of three months to five years and can already occur at slightly elevated temperature. For the parents, it is usually a shock when their child torments with fever and muscle twitching. Now, an international team of researchers led by experts from the Universities of Tübingen, Leuven and Luxembourg have succeeded in demonstrating a previously unknown cause for this most common form of epileptic seizure in infants.

Gene mutations lead to febrile convulsions
Thus, mutations in the gene STX1B are responsible for the pathological reactions to fever, as recently in the journal „Nature Genetics“ published study shows. These gene mutations lead to a disturbed regulation in the release of certain messenger substances of nerve cells. The result is increased, involuntary electrical discharges in the brain and thus epileptic febrile convulsions. In the long run, the newly discovered gene changes can also cause severe epilepsy and mental disability. Because of their discoveries, the scientists now hope to be able to develop new therapies.

Speed ​​of fever rise is crucial
It seems that the rate of fever rise is more crucial than the temperature. Professor Holger Lerche, board member at the Hertie Institute for Clinical Brain Research (HIH) at the University of Tübingen and medical director of the Department of Neurology with a focus on epileptology at the University Hospital Tübingen, said according to press reports: „This explains why children can have a febrile spell even before the parents even realize that their child is ill.“ Parents are naturally concerned if their child is prone to such attacks of fever, but the study's senior author, Professor Lerche, said: „Most of the small patients are less prone to seizures until school age.“

Genetic predisposition plays an important role
So far, little is known about the circumstances that contribute to the development of epilepsy from simple febrile seizures. „Genetic predisposition plays an important role in this. What changes in the genome are in detail, was previously poorly known“, said the co-initiator Professor Yvonne Weber, Senior Physician of the Department of Neurology with focus on Epileptology of the University Hospital Tübingen. By Exom sequencing, a study of a part of the genetic material, we know now more details. The exome accounts for about one percent of the human genome.

Results confirmed in animal experiments
First, analysis of the genetic material revealed STX1B mutations in two large families suffering from febrile seizures as well as epilepsy. In addition, other patients suffering from febrile convulsions and severe epilepsy were examined, with four other mutations detected. A total of 450 patients were included in the study. The research team confirmed the results in an animal model with zebrafish. „We were able to show that in zebrafish with genetically modified STX1B genes, seizure-like behavioral patterns and changes in the brain waves also occurred, which increased significantly when the temperature increased - as in the case of fever“, explained Camila Esguerra, who conducted the animal experiment at the University of Leuven. Dr. Alexander Crawford (Luxembourg), who, together with In an earlier study, Esguerra found a substance that can prevent the most severe seizures in zebrafish, saying: „We hope that within a few years, we will be able to develop a new drug that can prevent the development of certain forms of severe childhood epilepsy.“ (Ad)