KEGG   DISEASE: Early infantile epileptic encephalopathyHelp
Entry
H00606                      Disease                                

Name
Early infantile epileptic encephalopathy;
Ohtahara syndrome
  Subgroup
West syndrome [DS:H01460]
Lennox-Gastaut syndrome [DS:H01813]
PCDH19-related epilepsy syndrome [DS:H01775]
Malignant migrating partial seizures in infancy [DS:H01815]
  Supergrp
Symptomatic generalized epilepsies [DS:H00577]
Description
Early infantile epileptic encephalopathy (EIEE) is characterized by frequent tonic spasms of early onset within a few months of life, and a suppression-burst pattern in electroencephalography (EEG). Many causes have been considered for EIEE. It has been reported that 75% of the cases subsequently evolve to West syndrome, and later a much smaller number progress to Lennox-Gastaut syndrome.
Category
Nervous system diseases
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Epilepsy
   H00606  Early infantile epileptic encephalopathy
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Epilepsy or seizures
   8A62  Epileptic encephalopathies
    H00606  Early infantile epileptic encephalopathy
BRITE hierarchy
Pathway
hsa04723 Retrograde endocannabinoid signaling   
hsa04727 GABAergic synapse   
hsa04724 Glutamatergic synapse   
hsa04728 Dopaminergic synapse   
hsa04726 Serotonergic synapse   
Gene
(EIEE1) ARX [HSA:170302] [KO:K09452]
(EIEE2) CDKL5 [HSA:6792] [KO:K08824]
(EIEE3) SLC25A22 [HSA:79751] [KO:K15107]
(EIEE4) STXBP1 [HSA:6812] [KO:K15292]
(EIEE5) SPTAN1 [HSA:6709] [KO:K06114]
(EIEE7) KCNQ2 [HSA:3785] [KO:K04927]
(EIEE8) ARHGEF9 [HSA:23229] [KO:K20686]
(EIEE9) PCDH19 [HSA:57526] [KO:K16499]
(EIEE10) PNKP [HSA:11284] [KO:K08073]
(EIEE11) SCN2A1 [HSA:6326] [KO:K04834]
(EIEE12) PLCB1 [HSA:23236] [KO:K05858]
(EIEE13) SCN8A [HSA:6334] [KO:K04840]
(EIEE15) ST3GAL3 [HSA:6487] [KO:K00781]
(EIEE16) TBC1D24 [HSA:57465] [KO:K21841]
(EIEE17) GNAO1 [HSA:2775] [KO:K04534]
(EIEE18) SZT2 [HSA:23334]
(EIEE19) GABRA1 [HSA:2554] [KO:K05175]
(EIEE21) NECAP1 [HSA:25977] [KO:K20069]
(EIEE22) SLC35A2 [HSA:7355] [KO:K15272]
(EIEE23) DOCK7 [HSA:85440] [KO:K21852]
(EIEE24) HCN1 [HSA:348980] [KO:K04954]
(EIEE25) SLC13A5 [HSA:284111] [KO:K14445]
(EIEE26) KCNB1 [HSA:3745] [KO:K04885]
(EIEE27) GRIN2B [HSA:2904] [KO:K05210]
(EIEE28) WWOX [HSA:51741] [KO:K19329]
(EIEE29) AARS [HSA:16] [KO:K01872]
(EIEE30) SIK1 [HSA:150094] [KO:K19008]
(EIEE31) DNM1 [HSA:1759] [KO:K01528]
(EIEE32) KCNA2 [HSA:3737] [KO:K04875]
(EIEE33) EEF1A2 [HSA:1917] [KO:K03231]
(EIEE34) SLC12A5 [HSA:57468] [KO:K14427]
(EIEE35) ITPA [HSA:3704] [KO:K01519]
(EIEE36) ALG13 [HSA:79868] [KO:K07432]
(EIEE37) FRRS1L [HSA:23732]
(EIEE38) ARV1 [HSA:64801] [KO:K21848]
(EIEE40) GUF1 [HSA:60558] [KO:K21594]
(EIEE41) SLC1A2 [HSA:6506] [KO:K05613]
(EIEE42) CACNA1A [HSA:773] [KO:K04344]
(EIEE43) GABRB3 [HSA:2562] [KO:K05181]
(EIEE44) UBA5 [HSA:79876] [KO:K12164]
(EIEE45) GABRB1 [HSA:2560] [KO:K05181]
(EIEE46) GRIN2D [HSA:2906] [KO:K05212]
(EIEE47) FGF12 [HSA:2257] [KO:K22413]
(EIEE48) AP3B2 [HSA:8120] [KO:K12397]
(EIEE49) DENND5A [HSA:23258] [KO:K20164]
(EIEE51) MDH2 [HSA:4191] [KO:K00026]
(EIEE55) PIGP [HSA:51227] [KO:K03861]
(EIEE56) YWHAG [HSA:7532] [KO:K16198]
(EIEE57) KCNT2 [HSA:343450] [KO:K04947]
(EIEE60) CNPY3 [HSA:10695] [KO:K22816]
(EIEE61) ADAM22 [HSA:53616] [KO:K16068]
(EIEE62) SCN3A [HSA:6328] [KO:K04836]
(Lennox-Gastaut type) MAPK10 [HSA:5602] [KO:K04440]
Other DBs
ICD-11: 8A62.Y
ICD-10: G40.3
MeSH: C538670
OMIM: 308350 300672 609304 612164 613477 613720 300607 300088 613402 613721 613722 614558 615006 615338 615473 615476 615744 615833 300896 615859 615871 615905 616056 616139 616211 616339 616341 616346 616366 616409 616645 616647 300884 616981 617020 617065 617105 617106 617113 617132 617153 617162 617166 617276 617281 617339 617599 617665 617929 617933 617771
Reference
  Authors
Ohtahara S, Yamatogi Y
  Title
Epileptic encephalopathies in early infancy with suppression-burst.
  Journal
J Clin Neurophysiol 20:398-407 (2003)
Reference
  Authors
Ohtahara S, Yamatogi Y
  Title
Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy.
  Journal
Epilepsy Res 70 Suppl 1:S58-67 (2006)
DOI:10.1016/j.eplepsyres.2005.11.021
Reference
  Authors
Yamatogi Y, Ohtahara S
  Title
Early-infantile epileptic encephalopathy with suppression-bursts, Ohtahara syndrome; its overview referring to our 16 cases.
  Journal
Brain Dev 24:13-23 (2002)
DOI:10.1016/S0387-7604(01)00392-8
Reference
  Authors
Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, Uruno K, Kumada S, Nishiyama K, Nishimura A, Okada I, Yoshimura Y, Hirai S, Kumada T, Hayasaka K, Fukuda A, Ogata K, Matsumoto N
  Title
De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy.
  Journal
Nat Genet 40:782-8 (2008)
DOI:10.1038/ng.150
Reference
  Authors
Timal S, Hoischen A, Lehle L, Adamowicz M, Huijben K, Sykut-Cegielska J, Paprocka J, Jamroz E, van Spronsen FJ, Korner C, Gilissen C, Rodenburg RJ, Eidhof I, Van den Heuvel L, Thiel C, Wevers RA, Morava E, Veltman J, Lefeber DJ
  Title
Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing.
  Journal
Hum Mol Genet 21:4151-61 (2012)
DOI:10.1093/hmg/dds123
Reference
  Authors
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, 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
  Title
De novo mutations in epileptic encephalopathies.
  Journal
Nature 501:217-21 (2013)
DOI:10.1038/nature12439
Reference
  Authors
Edvardson S, Baumann AM, Muhlenhoff M, Stephan O, Kuss AW, Shaag A, He L, Zenvirt S, Tanzi R, Gerardy-Schahn R, Elpeleg O
  Title
West syndrome caused by ST3Gal-III deficiency.
  Journal
Epilepsia 54:e24-7 (2013)
DOI:10.1111/epi.12050
Reference
  Authors
Kodera H, Nakamura K, Osaka H, Maegaki Y, Haginoya K, Mizumoto S, Kato M, Okamoto N, Iai M, Kondo Y, Nishiyama K, Tsurusaki Y, Nakashima M, Miyake N, Hayasaka K, Sugahara K, Yuasa I, Wada Y, Matsumoto N, Saitsu H
  Title
De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy.
  Journal
Hum Mutat 34:1708-14 (2013)
DOI:10.1002/humu.22446
Reference
  Authors
Gonsales MC, Montenegro MA, Soler CV, Coan AC, Guerreiro MM, Lopes-Cendes I
  Title
Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice.
  Journal
Arq Neuropsiquiatr 73:946-58 (2015)
DOI:10.1590/0004-282X20150122
Reference
  Authors
McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE
  Title
The genetic landscape of the epileptic encephalopathies of infancy and childhood.
  Journal
Lancet Neurol 15:304-16 (2016)
DOI:10.1016/S1474-4422(15)00250-1
Reference
  Authors
Myers CT, McMahon JM, Schneider AL, Petrovski S
  Title
De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.
  Journal
Am J Hum Genet 99:287-98 (2016)
DOI:10.1016/j.ajhg.2016.06.003
Reference
  Authors
Torkamani A, Bersell K, Jorge BS, Bjork RL Jr, Friedman JR, Bloss CS, Cohen J, Gupta S, Naidu S, Vanoye CG, George AL Jr, Kearney JA
  Title
De novo KCNB1 mutations in epileptic encephalopathy.
  Journal
Ann Neurol 76:529-40 (2014)
DOI:10.1002/ana.24263
Reference
  Authors
Kevelam SH, Bierau J, Salvarinova R, Agrawal S, Honzik T, Visser D, Weiss MM, Salomons GS, Abbink TE, Waisfisz Q, van der Knaap MS
  Title
Recessive ITPA mutations cause an early infantile encephalopathy.
  Journal
Ann Neurol 78:649-58 (2015)
DOI:10.1002/ana.24496
Reference
  Authors
Shaheen R, Al Tala S, Ewida N, Abouelhoda M, Alkuraya FS
  Title
Epileptic encephalopathy with continuous spike-and-wave during sleep maps to a homozygous truncating mutation in AMPA receptor component FRRS1L.
  Journal
Clin Genet 90:282-3 (2016)
DOI:10.1111/cge.12796
Reference
  Authors
Palmer EE, Jarrett KE, Sachdev RK, Al Zahrani F, Hashem MO, Ibrahim N, Sampaio H, Kandula T, Macintosh R, Gupta R, Conlon DM, Billheimer JT, Rader DJ, Funato K, Walkey CJ, Lee CS, Loo C, Brammah S, Elakis G, Zhu Y, Buckley M, Kirk EP, Bye A, Alkuraya FS, Roscioli T, Lagor WR
  Title
Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy.
  Journal
Hum Mol Genet 25:3042-3054 (2016)
DOI:10.1093/hmg/ddw157
Reference
  Authors
Alfaiz AA, Muller V, Boutry-Kryza N, Ville D, Guex N, de Bellescize J, Rivier C, Labalme A, des Portes V, Edery P, Till M, Xenarios I, Sanlaville D, Herrmann JM, Lesca G, Reymond A
  Title
West syndrome caused by homozygous variant in the evolutionary conserved gene encoding the mitochondrial elongation factor GUF1.
  Journal
Eur J Hum Genet 24:1001-8 (2016)
DOI:10.1038/ejhg.2015.227
Reference
  Authors
Colin E, Daniel J, Ziegler A, Wakim J, Scrivo A, Haack TB, Khiati S, Denomme AS, Amati-Bonneau P, Charif M, Procaccio V, Reynier P, Aleck KA, Botto LD, Herper CL, Kaiser CS, Nabbout R, N'Guyen S, Mora-Lorca JA, Assmann B, Christ S, Meitinger T, Strom TM, Prokisch H, Miranda-Vizuete A, Hoffmann GF, Lenaers G, Bomont P, Liebau E, Bonneau D
  Title
Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy.
  Journal
Am J Hum Genet 99:695-703 (2016)
DOI:10.1016/j.ajhg.2016.06.030
Reference
  Authors
Li D, Yuan H, Ortiz-Gonzalez XR, Marsh ED, Tian L, McCormick EM, Kosobucki GJ, Chen W, Schulien AJ, Chiavacci R, Tankovic A, Naase C, Brueckner F, von Stulpnagel-Steinbeis C, Hu C, Kusumoto H, Hedrich UB, Elsen G, Hortnagel K, Aizenman E, Lemke JR, Hakonarson H, Traynelis SF, Falk MJ
  Title
GRIN2D Recurrent De Novo Dominant Mutation Causes a Severe Epileptic Encephalopathy Treatable with NMDA Receptor Channel Blockers.
  Journal
Am J Hum Genet 99:802-816 (2016)
DOI:10.1016/j.ajhg.2016.07.013
Reference
  Authors
Siekierska A, Isrie M, Liu Y, Scheldeman C, Vanthillo N, Lagae L, de Witte PA, Van Esch H, Goldfarb M, Buyse GM
  Title
Gain-of-function FHF1 mutation causes early-onset epileptic encephalopathy with cerebellar atrophy.
  Journal
Neurology 86:2162-70 (2016)
DOI:10.1212/WNL.0000000000002752
Reference
  Authors
Assoum M, Philippe C, Isidor B, Perrin L, Makrythanasis P, Sondheimer N, Paris C, Douglas J, Lesca G, Antonarakis S, Hamamy H, Jouan T, Duffourd Y, Auvin S, Saunier A, Begtrup A, Nowak C, Chatron N, Ville D, Mireskandari K, Milani P, Jonveaux P, Lemeur G, Milh M, Amamoto M, Kato M, Nakashima M, Miyake N, Matsumoto N, Masri A, Thauvin-Robinet C, Riviere JB, Faivre L, Thevenon J
  Title
Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.
  Journal
Am J Hum Genet 99:1368-1376 (2016)
DOI:10.1016/j.ajhg.2016.10.009
Reference
  Authors
Han C, Alkhater R, Froukh T, Minassian AG, Galati M, Liu RH, Fotouhi M, Sommerfeld J, Alfrook AJ, Marshall C, Walker S, Bauer P, Scherer SW, Riess O, Buchert R, Minassian BA, McPherson PS
  Title
Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A.
  Journal
Am J Hum Genet 99:1359-1367 (2016)
DOI:10.1016/j.ajhg.2016.10.006
Reference
  Authors
Ait-El-Mkadem S, Dayem-Quere M, Gusic M, Chaussenot A, Bannwarth S, Francois B, Genin EC, Fragaki K, Volker-Touw CL, Vasnier C, Serre V, van Gassen KL, Lespinasse F, Richter S, Eisenhofer G, Rouzier C, Mochel F, De Saint-Martin A, Abi Warde MT, de Sain-van der Velde MG, Jans JJ, Amiel J, Avsec Z, Mertes C, Haack TB, Strom T, Meitinger T, Bonnen PE, Taylor RW, Gagneur J, van Hasselt PM, Rotig A, Delahodde A, Prokisch H, Fuchs SA, Paquis-Flucklinger V
  Title
Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.
  Journal
Am J Hum Genet 100:151-159 (2017)
DOI:10.1016/j.ajhg.2016.11.014
Reference
  Authors
Johnstone DL, Nguyen TT, Murakami Y, Kernohan KD, Tetreault M, Goldsmith C, Doja A, Wagner JD, Huang L, Hartley T, St-Denis A, le Deist F, Majewski J, Bulman DE, Kinoshita T, Dyment DA, Boycott KM, Campeau PM
  Title
Compound heterozygous mutations in the gene PIGP are associated with early infantile epileptic encephalopathy.
  Journal
Hum Mol Genet 26:1706-1715 (2017)
DOI:10.1093/hmg/ddx077
Reference
  Authors
Guella I, McKenzie MB, Evans DM, Buerki SE, Toyota EB, Van Allen MI, Suri M, Elmslie F, Simon MEH, van Gassen KLI, Heron D, Keren B, Nava C, Connolly MB, Demos M, Farrer MJ
  Title
De Novo Mutations in YWHAG Cause Early-Onset Epilepsy.
  Journal
Am J Hum Genet 101:300-310 (2017)
DOI:10.1016/j.ajhg.2017.07.004
Reference
  Authors
Gururaj S, Palmer EE, Sheehan GD, Kandula T, Macintosh R, Ying K, Morris P, Tao J, Dias KR, Zhu Y, Dinger ME, Cowley MJ, Kirk EP, Roscioli T, Sachdev R, Duffey ME, Bye A, Bhattacharjee A
  Title
A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters Ion Selectivity and Causes Epileptic Encephalopathy.
  Journal
Cell Rep 21:926-933 (2017)
DOI:10.1016/j.celrep.2017.09.088
Reference
  Authors
Muona M, Fukata Y, Anttonen AK, Laari A, Palotie A, Pihko H, Lonnqvist T, Valanne L, Somer M, Fukata M, Lehesjoki AE
  Title
Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy.
  Journal
Neurol Genet 2:e46 (2016)
DOI:10.1212/NXG.0000000000000046

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