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Genetics of Epilepsy



  Quick links for this page:   More information about the research groups and programs affiliated with the Epilepsy Research Centre:
How do we study the genetics of epilepsy?
What happens next?
Our discoveries
How can I participate?
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Molecular Genetics Laboratory
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Clinical Genetics Research Group
University of Melbourne


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Paediatric Epilepsy, Autism & Mental Retardation Research
University of Melbourne

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The Epilepsy Genetics Group has been studying the inheritance of seizures in twins, families and sporadics for over 20 years.  The Epilepsy Genetics group comprises a large clinical epilepsy research team and the Epilepsy Molecular Genetics Laboratory.  Together with collaborators at the Women’s & Children’s Hospital and University of South Australia in Adelaide, and at the Walter and Eliza Hall Institute in Parkville, we are international leaders in the genetics of epilepsy. By 2011, 12000 people have participated in or signed up for 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, amongst 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 colleagues in Adelaide we are responsible for the discovery of 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.  By 2011 there were over twenty known "epilepsy genes", and our group is proud to have been involved in the identification of more than half of these. However, despite these findings, relatively little is known about the genetic causes of epilepsy in most people. The majority of 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.  However, we have been involved in some recent discoveries of susceptibility genes for common epilepsies and are excited about future progress in this area.

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How do we study the genetics of epilepsy?


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.

Families and individuals with epilepsy

Most known epilepsy genes have been identified by studying families where there are a large number of people who have had a seizure at some time in their lives. 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). DNA extraction and analysis is done either in our Molecular Genetics Laboratory here at the Epilepsy Research Centre by Dr Henrik Dahl and his team, or sent to our colleagues at the University of Adelaide (Dr Leanne Dibbens, Prof John Mulley and team). In large families detailed analysis is performed to try to determine which areas of DNA are shared by all the people in the family who have had seizures. This tells us where to start looking for genes that may play a role in causing the epilepsy in the family. Discovery of new genes can take many years of detailed study.

The information provided by smaller families and individuals is also crucial to our study. It is often necessary to look at a large number of people to see whether changes in a particular gene could be a common or rare cause of epilepsy. We can also make educated guesses about which genes may play a role in causing epilepsy and we need to look at a large number of people to see whether each gene is, or is not, relevant.

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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 Neurosciences Institutes, 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.

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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 the publications listed below.

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How can I participate?

Contact us and speak to one of our research assistants about whether it is appropriate for you to participate in this study.

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I am a doctor/researcher who would like to send some samples to you to be included in the study

Please Contact us and we will provide you with instructions for how to take and send samples to us. We require detailed clinical information to be provided before we can test any samples, including details of seizure types, age of onset and response to medication. EEG and MRI reports, clinical letters and other test results are also important.

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How is this research funded?

We currently receive funding from a research grant from the National Health and Medical Research Council of Australia.

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Research Positions

A complete listing of Epilepsy Research Centre staff can be found on our Staff page.

Opportunities exist for research in this area by those interested in clinical aspects of hereditary epilepsies for those with a neurology or genetics background.

We currently have positions available in our Molecular Genetics Laboratory for interested honours and PhD students. Details can be found on the Molecular Genetics Laboratory page under PhD and Honours Projects.

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Each year the Genetics Group releases a newsletter to update participants and other interested people on our activities and discoveries. If you would like to be added to our mailing list to receive this newsletter, or need to update your contact details please send an email to epilepsy-austin@unimelb.edu.au or contact us on (03) 9496 2737.
Alternatively, our newsletters can be downloaded via the following links and viewed with Acrobat Reader:

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Some of our important publications are listed below. More publications and details can be found using the search engine PubMed or on Prof Sam Berkovic and Prof Ingrid Scheffer's University of Melbourne Profiles.

Recent publications

  • Carranza Rojo D, Hamiwka L, McMahon JM, Dibbens LM, Arsov T, Suls A, Stodberg T, Kelley K, Wirrell EC, Appleton B, Mackay MT, Freeman JL, Yendle SC, Berkovic SF, Bienvenu T, De Jonghe P, Thorburn DR, Mulley JC, Mefford HC, Scheffer IE.  De Novo SCN1A mutations in Migrating Partial Seizures in Infancy.  Neurology 2011;77:380-3.
  • Mullen SA, Marini C, Suls A, Mei D, Della Giustina E, Buti D, Arsov A, Damiano J, Lawrence K, De Jonghe P, Berkovic SF, Guerrini R, Scheffer IE.  Glucose Transporter 1 Deficiency as a Treatable Cause of Myoclonic Astatic Epilepsy.  Arch Neurol. 2011 Sep;68(9):1152-5.
  • Crompton DE, Sadleir LG, Bromhead CJ, Bahlo M, Bellows ST, Arsov T, Harty R, Lawrence KM, Dunne JW, Berkovic SF, Scheffer IE.  Familial Adult Myoclonic Epilepsy (FAME): recognition of mild phenotypes and refinement of the 2q locus.  Arch Neurol (accepted 24 March 2011).
  • Catarino CB, Liu J, Liagkouras I, Gibbons VS, Labrum RW, Ellis R, Woodward C, Davis MB, Smith SJ, Cross JH, Appleton RE, Yendle SC, McMahon JM, Bellows ST, Jacques TS, Zuberi SM, Koepp MJ, Martinian L, Scheffer IE, Thom M, Sisodiya SM.  Dravet Syndrome as epileptic encephalopathy: evidence from very long-termcourse and neuropathology.  Brain 2011 Jun 29.
  • Dibbens LM, Kneen R, Bayla MA, Heron SE, Arsov T, Damiano JA, Desai T, Gibbs J, McKenzie F, Mulley JC, Ronan A, Scheffer IE.  Recurrence risk of epilepsy and MR in females due to parental mosaicism of PCDH19 mutations.  Neurology (accepted 19 January 2011).
  • Sadleir LG, Farrell K, Smith S, Connolly MB, Scheffer IE.  Electroclinical features of absence seizures in sleep.  Epilepsy Res 2011;93:216-20.
  • Klein KM, Yendle SC, Harvey AS, Antony JH, Wallace G, Bienvenu T, Scheffer IE.  A distinctive seizure type in patients with CDKL5 mutations: hypermotor-tonic-spasms sequence.  Neurology. 2011 Apr 19;76(16):1436-8.
  • Vadlamudi L, Dibbens LM, Lawrence KM, Iona X, McMahon JM, Murrell W, Mackay-Sim A, Scheffer IE, Berkovic SF.  Timing of de novo mutagenesis: a twin study of sodium channel mutations.  N Engl J Med 2010;363:1335-40.
  • Crompton DE, Scheffer IE, Taylor I, Cook MJ, McKelvie PA, Vears DF, Lawrence KM, McMahon JM, Grinton BE, McIntosh AM, Berkovic SF.  Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.  Brain 2010;133:3221-31.
  • Mullen SA, Suls A, De Jonghe P, Berkovic SF, Scheffer IE.  Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency.  Neurology 2010;75:432-40.
  • Dibbens LM, Mullen S, Helbig I, Mefford HC, Bayly MA, Bellows S, Leu C, Trucks H, Obermeier T, Wittig M, Franke A, Caglayan H, Yapici Z, EPICURE Consortium, Sander T, Eichler EE, Scheffer IE, Mulley JC, Berkovic SF.  Familial and sporadic 15q13.3 microdeletions in Idiopathic Generalized Epilepsy: Precedent for Disorders with Complex Inheritance.  Hum Mol Genet 2009;18:3626-31.
  • Taylor I, Berkovic SF, Kivity S, Scheffer IE.  Benign occipital epilepsies of childhood: clinical features and genetics.  Brain 2008;131:2287-2294.
  • Scheffer IE, Turner SJ, Dibbens LM, Bayly MA, Friend K, Hodgson B, Burrows I, Shaw M, Wei C, Ullman R, Ropers HH, Szepetowski P, Haan E, Mazarib A, Afawi Z, Neufeld MY, Andrews PI, Wallace G, Kivity S, Lev D, Lerman-Sagie T, Derry CP, Korezyn AD, Gecz J, Mulley JC, Berkovic SF.  Epilepsy and mental retardation limited to females: an under-recognized disorder.  Brain 2008;131:918-27.
  • Berkovic S.F., et al., Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. Am J Hum Genet, 2008. 82(3): p. 673-84.
  • Dibbens L.M., et al., X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet, 2008.
  • Helbig I., et al., Gene expression analysis in absence epilepsy using a monozygotic twin design. Epilepsia, 2008.
  • Helbig I., et al., Navigating the channels and beyond: unravelling the genetics of the epilepsies. Lancet Neurol, 2008. 7(3): p. 231-45.
  • Scheffer I.E., et al., Epilepsy and mental retardation limited to females: an under-recognized disorder. Brain, 2008. 131(Pt 4): p. 918-27.
  • Wallace R.H., et al., Somatic mutations in GLI3 can cause hypothalamic hamartoma and gelastic seizures. Neurology, 2008. 70(8): p. 653-5.
  • Brown N.J., et al., Vaccination, seizures and "vaccine damage". Current Opinions in Neurology, 2007. 20: p. 181-7 (invited review).
  • Dibbens L.M., et al., NEDD4-2 as a potential candidate susceptibility gene for epileptic photosensitivity. Genes Brain Behav, 2007. [Epub 23 Feb].
  • Gomez-Abad C., et al., Founder effect with variable age at onset in arab families with Lafora disease and EPM2A mutation. Epilepsia, 2007. 48: p. 1011-4.
  • Harkin L.A., et al. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain, 2007. 130: p. 843-52.
  • Herlenius E., et al., SCN2A Mutations and Benign Familial Neonatal-Infantile Seizures: The Phenotypic Spectrum. Epilepsia, 2007. 48: p. 1138-42.
  • Heron S.H., et al., Channelopathies in idiopathic epilepsy. Neurotherapeutics, 2007. 4: p. 295-304.
  • Heron S.H., et al., Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures. J Med Genet, 2007. [Epub 3 Aug].
  • Scheffer I.E., et al., Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain, 2007. 130: p. 100-9.
  • Taylor I., et al., Is photosensitive epilepsy less common in males due to variation in x chromosome photopigment genes? Epilepsia, 2007. 48: p. 1807-9.
  • Xu R., et al., A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel. Mol Cell Neurosci, 2007. 35: p. 292-301.
  • Xu R., et al., Epilepsy mutations in SCN1B reveal important residues for modulating slow inactivation in sodium channels. Neurobiology of Disease (in press, 2007).
  • Xu R., et al., GEFS+ associated SCN1B mutations cause loss of function. Neuroscience (in press, 2007).
  • Berkovic S.F., et al., De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study. Lancet Neurol, 2006. 5: p. 488-92.
  • Berkovic S.F., et al., Human epilepsies: interaction of genetic and acquired factors. Trends Neurosci, 2006. 29: p. 391-7.
  • Derry C.P., et al., Distinguishing sleep disorders from seizures: diagnosing bumps in the night. Arch Neurol, 2006. 63: p. 705-9. Erratum in: Arch Neurol, 2006. 63: p. 1037.
  • Jansen F.E., et al., Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis in adults. Neurology, 2006. 67: p.2224-6.
  • Mulley J.C., et al., A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A. Neurology, 2006. 67: p. 1094-5.
  • Vadlamudi L., et al., Analyzing the etiology of benign rolandic epilepsy: a multicenter twin collaboration. Epilepsia, 2006. 47: p. 550-5.
  • Vadlamudi L., et al., Action myoclonus-renal failure syndrome: a cause for worsening tremor in young adults. Neurology, 2006. 67: p. 1310-1.
  • Berkovic, S.F., et al., Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol, 2004. 55: p. 550-7.
  • Marini, C., et al., Genetic architecture of idiopathic generalized epilepsy: clinical genetic analysis of 55 multiplex families. Epilepsia, 2004. 45: p. 467-78.
  • Taylor, I., et al., Juvenile myoclonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap? Brain, 2004. 127: p. 1878-86.
  • Marini, C., et al., Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation. Brain, 2003. 126: p. 230-40.
  • Scheffer, I.E. and S.F. Berkovic, The genetics of human epilepsy. Trends Pharmacol Sci, 2003. 24: p. 428-33.
  • Wallace, R.H., et al., Sodium channel alpha 1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms. Neurology, 2003. 61: p. 765-769.
  • Harkin, L.A., et al., Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus. Am J Hum Genet, 2002. 70: p. 530-6.
  • Heron, S.E., et al., Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet, 2002. 360: p. 851-2.
  • Scheffer, I.E., et al., X-linked myoclonic epilepsy with spasticity and intellectual disability: mutation in the homeobox gene ARX. Neurology, 2002. 59: p. 348-56.
  • Wallace, R.H., et al., Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B. Neurology, 2002. 58: p. 1426-9.
  • Wallace, R.H., et al., Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet, 2001. 68: p. 859-65.
  • Wallace, R.H., et al., Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet, 2001. 28: p. 49-52.
  • Biervert, C., et al., A potassium channel mutation in neonatal human epilepsy. Science, 1998. 279: p. 403-6.
  • Wallace, R.H., et al., Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet, 1998. 19: p. 366-70.
  • Scheffer, I.E., et al., Familial partial epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2. Ann Neurol, 1998. 44: p. 890-9.
  • Scheffer, I.E. and S.F. Berkovic, Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain, 1997. 120: p. 479-90.
  • Scheffer, I.E., et al., Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. Brain, 1995. 118 : p. 61-73.
  • Steinlein, O.K., et al., A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet, 1995. 11: p. 201-3.

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Created: 15 Sept 2003
Last modified: 1 Feb 2012
Authorised by: Prof Sam Berkovic
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Maintained by: Susannah Bellows
Email: epilepsy-austin@unimelb.edu.au
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