Epileptic Encephalopathies: Finding the cause

Project Details

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 encepalopathies, with ongoing recruitment and clinical assessment.  This has led to the indentification of many novel genes for different forms of epileptic encephalopathies, however the cause in >60% of these patients remains unknown. Through detailed analysis of clinical and genetic features we have described new epileptic encaphalopathy 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.

Researchers

Collaborators

  • Associate Professor Heather Meffford, Division of Genetic Medicine, University of Washington, Seattle, USA

Funding

  • HUMAN EPILEPSY: UNDERSTANDING BIOLOGY TO IMPROVE OUTCOMES (Program Grants)  awarded by NHMRC 2016 - 2020

Research Publications

  • Epi4K Consortium.  De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies. Am J Hum Genet. 2016 Jul 27.  [Epub ahead of print].
  • Petrovski S, Küry S, Myers CT, Anyane-Yeboa K, Cogné B, Bialer M, Xia F, Hemati P, Riviello J, Mehaffey M, Besnard T, Becraft E, Wadley A, Politi AR, Colombo S, Zhu X, Ren Z, Andrews I, Dudding-Byth T, Schneider AL, Wallace G; University of Washington Center for Mendelian Genomics, Rosen AB, Schelley S, Enns GM, Corre P, Dalton J, Mercier S, Latypova X, Schmitt S, Guzman E, Moore C,  Bier L, Heinzen EL, Karachunski P, Shur N, Grebe T, Basinger A, Nguyen JM, Bézieau S, Wierenga K, Bernstein JA, Scheffer IE, Rosenfeld JA, Mefford HC, Isidor B, Goldstein DB. Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures. Am J Hum Genet. 2016 May  5;98(5):1001-10.
  • Howell KB, McMahon JM, Carvill GL, Tambunan D, Mackay MT, Rodriguez-Casero V, Webster R, Clark D, Freeman JL, Calvert S, Olson HE, Mandelstam S, Poduri A, Mefford HC, Harvey AS, Scheffer IE. SCN2A encephalopathy: a major cause of epilepsy of infancy with migrating focal seizures. Neurology 2015 Sep 15;85(11):958-66.
  • Carvill GL, McMahon JM, Schneider A, Zemel M, Myers C, Saykally J, Nguyen J, Robbiano A, Zara F, Specchio N, Mecarelli O, Smith RL, Leventer RJ, Møller RS, Nikanorova M, Dimova P, Jordanova A, Petrou S, Euroepinomics RES MAE/Dravet working group, Helbig I, Striano P, Weckhuysen S, Berkovic SF, Scheffer IE*, Mefford HC*. Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic atonic seizures. Am J Hum Genet 2015 May 7;96(5):808-15. * Equal senior author.
  • Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Møller RS, Hjalgrim H, Cook J, Geraghty E, O’Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Gazina EV, Suls A, Shendure J, De Jonghe P, Helbig I, Berkovic SF, Scheffer IE, Mefford HC. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology 2014 Apr 8;82(14):1245-53.
  • Carvill, GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, Khan A, O’Dorschner M, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AME, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC. Targeted resequencing in epileptic encephalopathies identifies recurrent de novo mutations in CHD2 and SYNGAP1.  Nat Genet 2013 Jul;45(7):825-30.
  • Epi4K Consortium, Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ; Epilepsy Phenome/Genome Project, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR. De novo mutations in epileptic encephalopathies. Nature 2013 Sep 12;501(7466):217-21.
  • Carvill GL, Regan BM, Yendle SC, O’Roak BJ, Lozovaya N, Bruneau N, Burnashev N, Khan A, Cook J, Geraghty E, Sadleir LG, Turner SJ, Tsai M-H, Webster R, Ouvrier R, Damiano J, Berkovic SF, Shendure J, Hildebrand M, Szepetowski P, Mefford HC, Scheffer IE. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat Genet 2013 Aug 28;45(9):1073-6.
  • Weckhuysen S, Mandelstam S, Sula A, Audenaert D, Deconinck T, Claes LR, Deprez L, Smets K, Hristova D, Yordanova I, Jordanova A, Ceulemans B, Jansen A, Hasaerts D, Roelens F, Lagae L, Yendle S, Stanley T, Heron SE, Mulley JC, Berkovic SF, De Jonghe P*,Scheffer IE*. KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy.  Ann Neurol 2012;71:15-25. * equal senior author
  • 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.


Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Medicine and Radiology