The spectrum of SCN1A-related infantile epileptic encephalopathies

Louise A. Harkin, Jacinta M. McMahon, Xenia Iona, Leanne Dibbens, James T. Pelekanos, Sameer M. Zuberi, Lynette G. Sadleir, Eva Andermann, Deepak Gill, Kevin Farrell, Mary Connolly, Thorsten Stanley, Michael Harbord, Frederick Andermann, Jing Wang, Sat Dev Batish, Jeffrey G. Jones, William K. Seltzer, Alison Gardner, Grant SutherlandSamuel F. Berkovic, John C. Mulley, Ingrid E. Scheffer, Kim Abbott, Ian Andrews, Barry Appleton, Andrew Bleasel, Neil Buchanan, Christopher Burke, Anne Bye, Carol Camfield, Peter Camfield, Gabriel Chow, Kevin Collins, Mark Cook, J. Helen Cross, Yanick Crow, M. Daniela D'Agostino, Martin Delatycki, Colin Dunkley, Joe Fawke, Colin Ferrie, Michael Geraghty, Gail Graham, Padraic Grattan-Smith, Elizabeth Hallam, Lorie Hamiwka, Anton Harding, Simon Harvey, Michael Hayman, Ian Hufton, Peter Humphries, Pierre Jacob, Raimond Jacquemard, David Jamison, Philip Jardine, Steve Jones, Daniel Keene, Kent Kelley, David Ketteridge, Andrew Kim, Sara Kivity, Chris Kneebone, Andrew Kornberg, Chris Lamb, Cecilie Lander, Tally Lerman-Sagie, Dorit Lev, Richard Leventer, Mark Mackay, Steven Malone, Jim Manson, Ailsa McLellan, Philip Moore, Lakshmi Nagarajan, Margot Nash, Marina Nikanorova, Doug Nordli, Mary O'Regan, Robert Ouvrier, Jayesh Patel, Clair Pridmore, Venkat Ramesh, David Reutens, Peter Rowe, Lloyd Shield, Paul Shillito, Lindsay Smith, Claire Spooner, Geoffrey Wallace, Nathan Watemberg, William Whitehouse, Elaine Wirrell

Research output: Contribution to journalArticle

354 Scopus citations

Abstract

The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.

Original languageEnglish (US)
Pages (from-to)843-852
Number of pages10
JournalBrain
Volume130
Issue number3
DOIs
StatePublished - Mar 1 2007

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Keywords

  • Channelopathies
  • Epileptic encephalopathy
  • SCN1A
  • SMEB
  • SMEI

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Harkin, L. A., McMahon, J. M., Iona, X., Dibbens, L., Pelekanos, J. T., Zuberi, S. M., Sadleir, L. G., Andermann, E., Gill, D., Farrell, K., Connolly, M., Stanley, T., Harbord, M., Andermann, F., Wang, J., Batish, S. D., Jones, J. G., Seltzer, W. K., Gardner, A., ... Wirrell, E. (2007). The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain, 130(3), 843-852. https://doi.org/10.1093/brain/awm002