The genetic landscape of the epileptic encephalopathies of infancy and childhood

被引：462

作者：

McTague, Amy ^{[1
,3
]}

Howell, Katherine B. ^{[4
,5
,6
]}

Cross, J. Helen ^{[2
,3
]}

Kurian, Manju A. ^{[1
,3
]}

Scheffer, Ingrid E. ^{[4
,5
,7
,8
]}

机构：

[1] UCL Inst Child Hlth, Dev Neurosci Programme, Mol Neurosci, London, England

[2] UCL Inst Child Hlth, Dev Neurosci Programme, Clin Neurosci, London, England

[3] Great Ormond St Hosp Children NHS Fdn Trust, Dept Neurol, London, England

[4] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia

[5] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia

[6] Murdoch Childrens Res Inst, Neurosci Grp, Melbourne, Vic, Australia

[7] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Austin Hlth, Melbourne, Vic, Australia

[8] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia

来源：

LANCET NEUROLOGY | 2016年 / 15卷 / 03期

基金：

英国医学研究理事会;

关键词：

SEVERE MYOCLONIC EPILEPSY; DE-NOVO MUTATIONS; MIGRATING PARTIAL SEIZURES; POTASSIUM CHANNEL GENE; COPY NUMBER VARIANTS; DRAVET SYNDROME; OHTAHARA SYNDROME; INTELLECTUAL DISABILITY; KCNQ2; ENCEPHALOPATHY; CLINICAL SPECTRUM;

D O I：

10.1016/S1474-4422(15)00250-1

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Epileptic encephalopathies of infancy and childhood comprise a large, heterogeneous group of severe epilepsies characterised by several seizure types, frequent epileptiform activity on EEG, and developmental slowing or regression. The encephalopathies include many age-related electrodinical syndromes with specific seizure types and EEG features. With the molecular revolution, the number of known monogenic determinants underlying the epileptic encephalopathies has grown rapidly. De-novo dominant mutations are frequently identified; somatic mosaicism and recessive disorders are also seen. Several genes can cause one electroclinical syndrome, and, conversely, one gene might be associated with phenotypic pleiotropy. Diverse genetic causes and molecular pathways have been implicated, involving ion channels, and proteins needed for synaptic, regulatory, and developmental functions. Gene discovery provides the basis for neurobiological insights, often showing convergence of mechanistic pathways. These findings underpin the development of targeted therapies, which are essential to improve the outcome of these devastating disorders.

引用

页码：304 / 316

页数：13

共 111 条

[1] A novel ARX phenotype: rapid neurodegeneration with Ohtahara syndrome and a dyskinetic movement disorder [J].

Absoud, Michael ;

Parr, Jeremy R. ;

Halliday, Dorothy ;

Pretorius, Pieter ;

Zaiwalla, Zenobia ;

Jayawant, Sandeep .

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY, 2010, 52 (03) :305-307

[2] De novo mutations in epileptic encephalopathies [J].

Allen, Andrew S. ;

Berkovic, Samuel F. ;

Cossette, Patrick ;

Delanty, Norman ;

Dlugos, Dennis ;

Eichler, Evan E. ;

Epstein, Michael P. ;

Glauser, Tracy ;

Goldstein, David B. ;

Han, Yujun ;

Heinzen, Erin L. ;

Hitomi, Yuki ;

Howell, Katherine B. ;

Johnson, Michael R. ;

Kuzniecky, Ruben ;

Lowenstein, Daniel H. ;

Lu, Yi-Fan ;

Madou, Maura R. Z. ;

Marson, Anthony G. ;

Mefford, Heather C. ;

Nieh, Sahar Esmaeeli ;

O'Brien, Terence J. ;

Ottman, Ruth ;

Petrovski, Slave ;

Poduri, Annapurna ;

Ruzzo, Elizabeth K. ;

Scheffer, Ingrid E. ;

Sherr, Elliott H. ;

Yuskaitis, Christopher J. ;

Abou-Khalil, Bassel ;

Alldredge, Brian K. ;

Bautista, Jocelyn F. ;

Berkovic, Samuel F. ;

Boro, Alex ;

Cascino, Gregory D. ;

Consalvo, Damian ;

Crumrine, Patricia ;

Devinsky, Orrin ;

Dlugos, Dennis ;

Epstein, Michael P. ;

Fiol, Miguel ;

Fountain, Nathan B. ;

French, Jacqueline ;

Friedman, Daniel ;

Geller, Eric B. ;

Glauser, Tracy ;

Glynn, Simon ;

Haut, Sheryl R. ;

Hayward, Jean ;

Helmers, Sandra L. .

NATURE, 2013, 501 (7466) :217-+

[3] De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies [J].

Appenzeller, Silke ;

Balling, Rudi ;

Barisic, Nina ;

Baulac, Stephanie ;

Caglayan, Hande ;

Craiu, Dana ;

De Jonghe, Peter ;

Depienne, Christel ;

Dimova, Petia ;

Djemie, Tania ;

Gormley, Padhraig ;

Guerrini, Renzo ;

Helbig, Ingo ;

Hjalgrim, Helle ;

Hoffman-Zacharska, Dorota ;

Jaehn, Johanna ;

Klein, Karl Martin ;

Koeleman, Bobby ;

Komarek, Vladimir ;

Krause, Roland ;

Kuhlenbaeumer, Gregor ;

Leguern, Eric ;

Lehesjoki, Anna-Elina ;

Lemke, Johannes R. ;

Lerche, Holger ;

Linnankivi, Tarja ;

Marini, Carla ;

May, Patrick ;

Moller, Rikke S. ;

Muhle, Hiltrud ;

Pal, Deb ;

Palotie, Aarno ;

Pendziwiat, Manuela ;

Robbiano, Angela ;

Roelens, Filip ;

Rosenow, Felix ;

Selmer, Kaja ;

Serratosa, Jose M. ;

Sisodiya, Sanjay ;

Stephani, Ulrich ;

Sterbova, Katalin ;

Striano, Pasquale ;

Suls, Arvid ;

Talvik, Tiina ;

von Spiczak, Sarah ;

Weber, Yvonne ;

Weckhuysen, Sarah ;

Zara, Federico ;

Abou-Khalil, Bassel ;

Alldredge, Brian K. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2014, 95 (04) :360-370

[4]

Azzarito V, 2013, NAT CHEM, V5, P161, DOI [10.1038/nchem.1568, 10.1038/NCHEM.1568]

[5] De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy [J].

Barcia, Giulia ;

Fleming, Matthew R. ;

Deligniere, Aline ;

Gazula, Valeswara-Rao ;

Brown, Maile R. ;

Langouet, Maeva ;

Chen, Haijun ;

Kronengold, Jack ;

Abhyankar, Avinash ;

Cilio, Roberta ;

Nitschke, Patrick ;

Kaminska, Anna ;

Boddaert, Nathalie ;

Casanova, Jean-Laurent ;

Desguerre, Isabelle ;

Munnich, Arnold ;

Dulac, Olivier ;

Kaczmarek, Leonard K. ;

Colleaux, Laurence ;

Nabbout, Rima .

NATURE GENETICS, 2012, 44 (11) :1255-1259

[6] Cognitive decline in Dravet syndrome: Is there a cerebellar role? [J].

Battaglia, Domenica ;

Chieffo, Daniela ;

Siracusano, Rosamaria ;

de Waure, Chiara ;

Brogna, Claudia ;

Ranalli, Domiziana ;

Contaldo, Ilaria ;

Tortorella, Gaetano ;

Dravet, Charlotte ;

Mercuri, Eugenio ;

Guzzetta, Francesco .

EPILEPSY RESEARCH, 2013, 106 (1-2) :211-221

[7] The incidence of SCN1A-related Dravet syndrome in Denmark is 1: 22,000: A population-based study from 2004 to 2009 [J].

Bayat, Allan ;

Hjalgrim, Helle ;

Moller, Rikke S. .

EPILEPSIA, 2015, 56 (04) :E36-E39

[8] Targeted Treatment of Migrating Partial Seizures of Infancy with Quinidine [J].

Bearden, David ;

Strong, Alanna ;

Ehnot, Jessica ;

DiGiovine, Marissa ;

Dlugos, Dennis ;

Goldberg, Ethan M. .

ANNALS OF NEUROLOGY, 2014, 76 (03) :457-461

[9] Focal Scn1a knockdown induces cognitive impairment without seizures [J].

Bender, Alex C. ;

Natola, Heather ;

Ndong, Christian ;

Holmes, Gregory L. ;

Scott, Rod C. ;

Lenck-Santini, Pierre-Pascal .

NEUROBIOLOGY OF DISEASE, 2013, 54 :297-307

[10] Accurate whole human genome sequencing using reversible terminator chemistry [J].

Bentley, David R. ;

Balasubramanian, Shankar ;

Swerdlow, Harold P. ;

Smith, Geoffrey P. ;

Milton, John ;

Brown, Clive G. ;

Hall, Kevin P. ;

Evers, Dirk J. ;

Barnes, Colin L. ;

Bignell, Helen R. ;

Boutell, Jonathan M. ;

Bryant, Jason ;

Carter, Richard J. ;

Cheetham, R. Keira ;

Cox, Anthony J. ;

Ellis, Darren J. ;

Flatbush, Michael R. ;

Gormley, Niall A. ;

Humphray, Sean J. ;

Irving, Leslie J. ;

Karbelashvili, Mirian S. ;

Kirk, Scott M. ;

Li, Heng ;

Liu, Xiaohai ;

Maisinger, Klaus S. ;

Murray, Lisa J. ;

Obradovic, Bojan ;

Ost, Tobias ;

Parkinson, Michael L. ;

Pratt, Mark R. ;

Rasolonjatovo, Isabelle M. J. ;

Reed, Mark T. ;

Rigatti, Roberto ;

Rodighiero, Chiara ;

Ross, Mark T. ;

Sabot, Andrea ;

Sankar, Subramanian V. ;

Scally, Aylwyn ;

Schroth, Gary P. ;

Smith, Mark E. ;

Smith, Vincent P. ;

Spiridou, Anastassia ;

Torrance, Peta E. ;

Tzonev, Svilen S. ;

Vermaas, Eric H. ;

Walter, Klaudia ;

Wu, Xiaolin ;

Zhang, Lu ;

Alam, Mohammed D. ;

Anastasi, Carole .

NATURE, 2008, 456 (7218) :53-59

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