Not all SCN1A epileptic encephalopathies are Dravet syndrome

著者: Lynette G. Sadleir, Emily Mountier, Deepak Gill, Suzanne L. Davis, Charuta Joshi, Catherine DeVile, Manju A. Kurian, For the DDD Study, Simone Mandelstam, Elaine Wirrell, Katherine Nickels, Hema Murali, Gemma L. Carvill, Candace T. Myers, Heather C. Mefford, Ingrid E. Scheffer, DDD Study, A. Paul Bevan, Abhijit Dixit, Abigail Pridham, Adrian R. Tivey, Ajoy Sarkar, Alan Donaldson, Alan Fryer, Alejandro Sifrim, Alex Henderson, Alex Magee, Alexis E. Duncan, Alison Kraus, Alison Male, Alison Ross, Amanda Collins, Anand Saggar, Andrea Coates, Andrea H. Németh, Andrew E. Fry, Andrew Green, A. Jackson, Andrew Norman, Angela Barnicoat, Angela Brady, Angela Douglas, Angus Clarke, Angus Dobbie, Ann Selby, Anna Middleton, Anne Lampe, A Seller, Annie Procter, Karenza Evans, Anthony Vandersteen, Astrid Weber, Audrey Smith, Audrey Torokwa, Beckie Kaemba, Becky Treacy, Beiyuan Fu, Ben Hutton, Birgitta Bernhard, Bronwyn Kerr, Bruce Castle, Carina Donnelly, Carol Gardiner, Carol Scott, Carole Brewer, Caroline F. Wright, Caroline Langman, Caroline Mackie Ogilvie, Caroline Pottinger, Carolyn Tysoe, Cat Taylor, Catherine McWilliam, Charles Shaw‐Smith, Charu Deshpande, Cheryl Longman, Cheryl Sequeira, Chirag Patel, Chris Bennett, Chris Nellåker, Christopher Wragg, Claire Kirk, Claire Turner, Daniel A. King, Daniel M. Barrett, Daniel Perrett, Daniela T. Pilz, Danielle Walker, David Baty, David Bohanna, David Bourn, David Goudie, David J. Bunyan, David Jones, David Moore, David Fitzpatrick, David Fitzpatrick, Debbie Rice, Debbie Shears, Deirdre Cilliers, Deirdre Donnelly, Denise Williams, Derek Lim, Dhavendra Kumar, Emma McCann, Dian Donnai, Diana Baralle, Diana Johnson, Diana Rajan, Diana Wellesley, Dominic McMullan, Douglas J. Simpkin, Dragana Josifova, Dylan H. de Vries, Eamonn Sheridan, E.R. Maher, Edward Blair, Eileen Roberts, Elena Chatzimichali, Elena Prigmore, Elisabeth Rosser, Elizabeth A. Jones, Elizabeth Sweeney, Emily Wilkinson, Emma Gray, Pipelines Staff, Emma Hobson, Emma Kivuva, Emma Miles, Emma Shearing, Emma Wakeling, Esther Kinning, Eugene Bragin, Eve L. Coomber, Fentang Yang, Fiona Connell, Fiona Stewart, Frances Elmslie, Frances Flinter, G. Jawahar Swaminathan, Gail Kirby, Gareth Cross, Gemma Devlin, Geoff Woods, Georgina Hollingsworth, Gillian Roberts, Gordon R. Lowther, Harinder Gill, Hayley Archer, Helen Cox, Helen V. Firth, Helen Kingston, Helen Murphy, Helen Stewart, Helen V. Firth, Hellen Purnell, Hood Mugalaasi, Ian O. Ellis, Ingrid Scurr, Ingrid Simonic, Irina Colgiu, Jacqueline Eason, Jana Awada, Jane A. Hurst, Jeffrey C. Barrett, Jenny Morton, Jenny Thomson, Jeremy F. McRae, Jill Clayton‐Smith, Joan Paterson, Joanna Jarvis, Joanna Kaplanis, Joanna Poulton, John Burn, John L. Burton, John Dean, John Tolmie, Jonathan S. Berg, Jonathan Roberts, Jonathon Waters, Josh Randall, Judith Goodship, Julia Rankin, Julian R. Sampson, Julie Phipps, Julie Vogt, Kai‐Ren Ong, Karen Marks, Kate Brunstrom, Kate Chandler, Kate Tatton‐Brown, Kath Smith, Katherine I. Morley, Katherine Lachlan, I. Karen Temple, Katherine Martin, Katrina Prescott, Kay Metcalfe, Kirsten McKay, Kirsty Ambridge, Lara Cresswell, Laura E. Mason, Laura Yates, Leema Robert, Lily Islam, Linda Sneddon, Lisa C. Bradley, Liu He, Lorraine Gaunt, Louise Bourdon, Louise Brueton, Louise Nevitt, Louise Wilson, Lucy Harrison, Lucy Hilyard, Lucy Jenkins, Lucy Raymond, Lynn Greenhalgh, Marc Tischkowitz, Margo Whiteford, Margriet van Kogelenberg, Maria Bitner‐Glindzicz, Mariella D’Alessandro, Martin Pollard, Matthew E. Hurles, Meena Balasubramanian, Melissa Lees, Melita Irving, Meriel McEntagart, Mervyn Humphreys, Michael W. Parker, Michael Parker, Michael Parker, Michael Wright, Michael Yau, Miranda Splitt, Miranda Squires, Mohnish Suri, Mohsan Alvi, Moira Blyth, Morag N. Collinson, Munaza Ahmed, Muriel Holder, Nadia Akawi, Natalie Canham, Neeti Ghali, Netravathi Krishnappa, Nicola Cooper, Nicola Foulds, Nicola Ragge, Nicola Williams, Nigel P. Carter, Nora Shannon, Norman Pratt, Oliver Quarrell, Paul Batstone, Paul Roberts, Peter Ellis, Peter D. Turnpenny, Philip Greene, P. D. Jones, Pradeep Vasudevan, Rachel Harrison, Raheleh Rahbari, Ray Miller, Richard Fisher, Richard J. Gibbons, Richard Sandford, Richard Scott, Robert Andrews, Rohan Taylor, Roldan Singzon, Rose Hawkins, Rosemarie Davidson, Rosemary E. Kelsell, Rosie O’Shea, Ruby Banerjee, Ruth Armstrong, Ruth McGowan, Ruth Newbury‐Ecob, Saba Sharif, Mark Tein, Saeed Al-Turki, Sahar Mansour, Sally Ann Lynch, Sally Davies, Sandra Kazembe, Sandra Louzada Gomes Pereira, Sara Widaa, Sarah Edkins, Sarah Everest, Sarah Hewitt, Sarah Smithson, Sarah Wallwark, Sarah Wilcox, Sarju Mehta, Sebastian S. Gerety, Shalaka Samant, Shane McKee, Shehla Mohammed, Shelagh Joss, Sian Ellard, Siân Morgan, Siddharth Banka, Simon Brent, Simon Holden, Sofia Douzgou, Soo‐Mi Park, Stephen Clayton, Stephen Hellens, Stewart J. Payne, Stuart Aitken, Stuart Ingram, Sue Price, Susan Clasper, Susan Gribble, Susan Holder, Susan McNerlan, Susan Tomkins, Susann Schweiger, Suzannah J. Bumpstead, Swati Naik, Tabib Dabir, Tanya Bayzetinova, Tara Montgomery, Tarjinder Singh, Tessa Homfray, Tina Fendick, Tomas Fitzgerald, Tomas Fitzgerald, Trevor Cole, Una Maye, Uruj Anjum, Usha Kini, Vipul Kumar, Victoria Harrison, Victoria Murday, Vijaya Parthiban, Vinod Varghese, Virginia Clowes, Vivienne McConnell, V. Reid Sutton, Volker Straub, Wayne Lam, Wendy D. Jones, Yanick J. Crow, Zara Skitt, Zosia Miedzybrodzka - Neurology 2017 被引用: 127

Objective: To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder. Methods: A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation. Results: We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable. Conclusions: Here, we present a phenotype-genotype correlation for SCN1A. We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met.