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Febrile seizures in small children to be fully investigated

A major scientific study funded by the Lundbeck Foundation will analyse the genetics underlying febrile seizures – and seek to answer a question that has long challenged scientists: Do febrile seizures increase the risk of developing epilepsy later in life?

Any parent’s alarm bells will begin to ring when their babies or toddlers have febrile seizures – and not without reason, because they are extremely dramatic.

It all begins with a fever – a relatively high temperature of the non-specific kind, common to very young children and familiar to most parents. But then things suddenly change, without warning: the child’s body becomes stiff, almost rigid, and its legs and arms may twitch while the head rolls back, breathing becomes laboured and the skin turns very pale or bluish. During a seizure, it will typically be very difficult to engage with the child, which of course heightens the parents’ panic.

The child must immediately be examined by a doctor, and the outcome of this is usually a brief admission to hospital. On the positive side, febrile seizures – which predominantly affect children between the ages of six months and five years – rarely have any side effects.

Bjarke Feenstra, senior scientist at Statens Serum Institut (SSI), explains that around 4% of all Danish children develop febrile seizures, and similar incidence is seen in many other countries:

‘Simply put, this means that one child in every school class in Denmark has experienced febrile seizures. But we’ve no idea why some children are susceptible to these seizures while the great majority are not. We’ll now try to collect new data on this and, at the same time, seek to identify whether febrile seizures increase the risk of developing epilepsy later in life,’ says Bjarke Feenstra, who is an expert in the genetic factors underlying disease evolution.

His study, which has received a grant of DKK 5 million through the Lundbeck Foundation Ascending Investigators research programme, will run until 2024, and Bjarke Feenstra will collaborate with a number of colleagues in Denmark, Norway and Australia.

Danish patient data
Volume is a keyword when it comes to investigating factors related to disease and health. It’s all about studying as many people as possible – both sick and healthy – and then, among other things, identifying the differences between the two groups.
Basically, these differences are interesting because they could potentially help explain why some people contract a disease or have a certain health condition while others are spared – as is the case with febrile seizures.

‘Our study will be the largest genetic study of febrile seizures ever conducted,’ says Bjarke Feenstra. ‘We’ll examine the DNA of 10,000 children who’ve experienced febrile seizures and then compare their profiles with similar genetic material taken from 100,000 controls who didn’t have febrile seizures in early childhood.’

Bjarke Feenstra explains that this is done by mapping the entire genetic material of all 110,000 people and, in each case, looking closely at the one million locations in the DNA where there could be genetic variations between individuals.

‘This study will map the genetic variants in the DNA of a very large number of people and will pinpoint those that – with a high level of statistical certainty – have something to do with the disease or health condition being studied.’

Large volumes of the patient data included in the study – both treatment data and DNA samples – come from health registries linked to the Danish civil registration (CPR) system. These are extremely sensitive personal data, and scientists can seek access to the data in anonymised format.

Bjarke Feenstra and his colleagues will use registries such as the Danish National Patient Registry, the Danish Blood Donor Study and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) in their attempts to improve their understanding of febrile seizures.

The study will also use genetic data taken from the Norwegian Mor-Og-Barn (Mother-And-Child) study, and Australian scientists from the University of Melbourne will contribute genetic profiles related to both epilepsy and febrile seizures.

‘We really hope to be able get closer to removing the question mark over links between febrile seizures and later development of epilepsy,’ says Bjarke Feenstra:

‘We know from other studies that 5-7% of the children who have febrile seizures develop epilepsy in later life. We’ll compare the genetic profiles of these children with profiles of children who had febrile seizures but never developed epilepsy. And the question is, of course, whether the group who developed epilepsy are genetically different in some way or other.’

New therapies and drugs
Bjarke Feenstra says that once the scientists have conducted DNA analyses to identify the variations in genetic make-up that have an impact on febrile seizures and epilepsy, the next step is obvious:

‘It’s a question of identifying which biological mechanisms are affected by these genetic variations. We can seek to establish this by investigating whether there’s any other information about these genetic variations in scientific literature or large databases containing the outcomes of other studies.’

‘And, of course, we hope to be able to contribute new knowledge which, in time, can be used to develop better prevention and treatment of both epilepsy and febrile seizures,’ says Bjarke Feenstra.

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