Genetics of Epilepsy

The Epilepsy Genetics Group has been studying the inheritance of seizures in twins, families and individuals for over 25 years. The Epilepsy Genetics group comprises a large clinical epilepsy research team and the Epilepsy Molecular Genetics Laboratory.  Together with collaborators at the University of Adelaide, the Walter and Eliza Hall Institute and colleagues around the world, we are international leaders in the genetics of epilepsy. So far more than 20,000 people have participated in our research studies.

Although epilepsy can be acquired in some people (through a severe head injury for example), there is strong evidence that genetic factors may cause or contribute to many types of epilepsy. There is often a family history of epilepsy or seizures in patients with certain types of epilepsy. Similarly, among twins with epilepsy, it is more common for identical twins to both experience seizures than for non-identical twins.  We believe that by identifying genes and understanding the basic molecular mechanisms of the inherited epilepsies we will gain a deeper understanding into the disorder, with implications for diagnosis and development of more effective treatments.

Together with our molecular genetics colleagues we identified the first epilepsy gene (a nicotinic receptor subunit CHRNA4) in 1995 and since then we have continued to be the international leaders in gene discovery for epilepsy. Over the last 20 years, there has been a virtual explosion in the number of genes linked with epilepsy, with more than 400 genes associated with seizures.

 

However, despite these findings, there is still much more to discover. The genetic cause is still unknown in the majority of people with epilepsy. Many genes that have been identified so far either cause very rare types of epilepsy or are rare causes of the more common types of epilepsy. In addition, we believe that the common genetic epilepsies are caused by a number of genes acting together, making it much harder to identify each individual gene.  We are excited about future progress in this area and continue our research efforts to uncover more genetic causes of epilepsy as well as understanding how these causes disrupt the normal function of the brain to cause seizures.

How do we study the genetics of epilepsy?
Families and individuals with epilepsy

Studying families with a large number of people who have had a seizure at some time in their lives has been a very successful way of finding epilepsy genes. While these families give us the best chance of finding these genes, they are quite rare. We also study smaller families where there are only a few people who have had seizures, and also individuals with no family history at all.

In all genetic epilepsy studies it is very important to determine exactly who has epilepsy, the type of epilepsy each person has and whether everyone in the family has similar or different types of epilepsy or seizures.  This involves conducting a detailed questionnaire with as many people from the family as possible and may sometimes involve further testing such as an EEG (brainwave reading) or MRI (brain imaging) scan. We then request a blood sample from the participants, which is used to extract DNA (genetic material). There are many ways the DNA can be analysed - sometimes all the samples from a family will be studied together to track down the responsible gene, sometimes a single DNA sample can be studied on its own and sometimes the sample might be studied together with samples from many other people with the same type of epilepsy. Discovery of new genes can take many years of detailed study.

 

Twins

Twins do not have a greater chance of having epilepsy than the general population, but twins can provide special insights into the causes of epilepsy. Because identical twins share the same genes, and all twins typically share the same environment, studying twins where one or both have seizures or epilepsy can help us distinguish genetic causes of epilepsy from other causes.

Developmental and epileptic encephalopathies

Developmental and epileptic encephalopathies are rare severe disorders in which infants or children have multiple different types of seizures that are extremely difficult to control.  They are usually accompanied by slowing in development, sometimes with loss of skills. We have assembled a large cohort of patients with epileptic encephalopathies, with ongoing recruitment and clinical assessment.  This has led to the identification of many novel genes for different forms of epileptic encephalopathies, however the cause in >50% of these patients remains unknown. Through detailed analysis of clinical and genetic features we have described new epileptic encephalopathy syndromes and analysed the relationship between specific types of epilepsy and the causative genes. More answers regarding the causes and therapies for epileptic encephalopathies will emerge with our ongoing work.

What happens next?

Once a gene is identified we attempt to understand how it causes epilepsy. This is done by a number of methods including replicating the changes we see in the gene in simple systems (such as single cells) or in whole animals. We have a group of talented collaborators at the University of Melbourne, the Florey Institute of Neuroscience and Mental Health, and internationally who are helping us with this.

We hope that understanding how these genes cause epilepsy will lead to a deeper understanding of epilepsy and possibly new treatments. The development of new treatments may take many years, but the genetic research and the blood samples we collect are the important beginning.

Our Discoveries

Since we started investigating the genetics of epilepsy we have been involved in making many important discoveries. These include describing several genetic epilepsy syndromes (such as Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) and Generalised Epilepsy with Febrile Seizures Plus (GEFS+)), and being involved in the localization or identification of several epilepsy genes.

 

Our extensive work in this area has contributed to the development of the concept of channelopathies ("diseases of ion channels") being the underlying cause of many idiopathic (genetic) epilepsies. More details regarding our findings are available in our annual newsletters and publications.

How is the research funded?

We currently receive funding from research grants from the National Health and Medical Research Council of Australia as well as from small philanthropic organisations and individuals.

No matter what size your donation is, the amount is greatly appreciated and will be used for the sole purpose of investigating epilepsy to achieve the optimum results for those with epilepsy and their families and friends. To find out more about the impact of giving or how to donate click here.

Project Highlights

 

The importance of genetics factors

Detecting somatic mutations in sporadic epilepsies

Sudden Unexpected Death in Epilepsy

Clinical Group

 

Professor Sam Berkovic

AC | FAHMS | FAA | FRACP | FRS

Professor of Neurology, The University of Melbourne and Florey Institute, Director of the Comprehensive Epilepsy Program, Austin Health

More about Sam

Professor Ingrid Scheffer

AO | FAHMS | FAA | FRACP | FRS

Professor of Paediatric Neurology, The University of Melbourne and Florey Institute, Austin Health and the Royal Children's Hospital, Melbourne

More about Ingrid

Amy Schneider

Rosie Burgess

Rebekah Harris

Lisa Johnson

PA to Sam Berkovic

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Bronwyn Grinton

Stephanie Leech

Marie Inder

Natasha Crawford

Stephanie Hart

EA to Ingrid Scheffer

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Brigid Regan