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Macrocephaly and epileptic encephalopathy

MedGen UID:
813871
Concept ID:
C3807541
Disease or Syndrome
Synonym: Encephalopathy of childhood
 
OMIM®: 606369

Definition

Lennox-Gastaut syndrome is a severe condition characterized by repeated seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, developmental delays, and particular patterns of brain activity measured by a test called an electroencephalogram (EEG). An EEG shows a slow spike-and-wave pattern during wakefulness and generalized paroxysmal fast activity during sleep.

In people with Lennox-Gastaut syndrome, epilepsy begins in early childhood, usually between ages 3 and 5. The most common seizure type is tonic seizures, which cause the muscles to stiffen (contract) uncontrollably. These seizures typically occur during sleep; they may also occur during wakefulness. Also common are atonic seizures, which are caused by a sudden loss of muscle tone. Tonic and atonic seizures can cause sudden falls that can result in serious or life-threatening injuries. Additionally, many affected individuals have atypical absence seizures, which cause a very brief partial or complete loss of consciousness. Other types of seizures have been reported less frequently in people with Lennox-Gastaut syndrome. Seizures associated with Lennox-Gastaut syndrome often do not respond well to therapy with anti-epileptic medications.

Although each seizure episode associated with Lennox-Gastaut syndrome is usually brief, more than two-thirds of affected individuals experience prolonged periods of seizure activity (known as status epilepticus) or episodes of many seizures that occur in a cluster.

About one-third of people with Lennox-Gastaut syndrome have normal intellectual development before seizures begin. The remainder have intellectual disability or learning problems even before seizures arise. Intellectual problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems. Many are also slow to develop motor skills such as sitting and crawling. As a result of their seizures and intellectual disability, most people with Lennox-Gastaut syndrome require help with daily activities. However, a small percentage of affected adults can live independently.

People with Lennox-Gastaut syndrome have a higher risk of death than their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures, pneumonia resulting from inhaling saliva (aspiration pneumonia) during a seizure, and injuries from falls. In addition, individuals with Lennox-Gastaut syndrome are at risk of sudden unexpected death in epilepsy (SUDEP), which describes sudden death with no known cause in someone with epilepsy; it is not the direct result of a seizure. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Marchese M, Conti V, Valvo G, Moro F, Muratori F, Tancredi R, Santorelli FM, Guerrini R, Sicca F
BMC Med Genet 2014 Feb 27;15:26. doi: 10.1186/1471-2350-15-26. PMID: 24580998Free PMC Article
Steenweg ME, Jakobs C, Errami A, van Dooren SJ, Adeva Bartolomé MT, Aerssens P, Augoustides-Savvapoulou P, Baric I, Baumann M, Bonafé L, Chabrol B, Clarke JT, Clayton P, Coker M, Cooper S, Falik-Zaccai T, Gorman M, Hahn A, Hasanoglu A, King MD, de Klerk HB, Korman SH, Lee C, Meldgaard Lund A, Mejaski-Bosnjak V, Pascual-Castroviejo I, Raadhyaksha A, Rootwelt T, Roubertie A, Ruiz-Falco ML, Scalais E, Schimmel U, Seijo-Martinez M, Suri M, Sykut-Cegielska J, Trefz FK, Uziel G, Valayannopoulos V, Vianey-Saban C, Vlaho S, Vodopiutz J, Wajner M, Walter J, Walter-Derbort C, Yapici Z, Zafeiriou DI, Spreeuwenberg MD, Celli J, den Dunnen JT, van der Knaap MS, Salomons GS
Hum Mutat 2010 Apr;31(4):380-90. doi: 10.1002/humu.21197. PMID: 20052767
Almgren M, Schalling M, Lavebratt C
Eur J Paediatr Neurol 2008 Nov;12(6):438-45. Epub 2008 Jan 31 doi: 10.1016/j.ejpn.2007.11.008. PMID: 18242108

Recent clinical studies

Etiology

Stephenson SEM, Costain G, Blok LER, Silk MA, Nguyen TB, Dong X, Alhuzaimi DE, Dowling JJ, Walker S, Amburgey K, Hayeems RZ, Rodan LH, Schwartz MA, Picker J, Lynch SA, Gupta A, Rasmussen KJ, Schimmenti LA, Klee EW, Niu Z, Agre KE, Chilton I, Chung WK, Revah-Politi A, Au PYB, Griffith C, Racobaldo M, Raas-Rothschild A, Ben Zeev B, Barel O, Moutton S, Morice-Picard F, Carmignac V, Cornaton J, Marle N, Devinsky O, Stimach C, Wechsler SB, Hainline BE, Sapp K, Willems M, Bruel AL, Dias KR, Evans CA, Roscioli T, Sachdev R, Temple SEL, Zhu Y, Baker JJ, Scheffer IE, Gardiner FJ, Schneider AL, Muir AM, Mefford HC, Crunk A, Heise EM, Millan F, Monaghan KG, Person R, Rhodes L, Richards S, Wentzensen IM, Cogné B, Isidor B, Nizon M, Vincent M, Besnard T, Piton A, Marcelis C, Kato K, Koyama N, Ogi T, Goh ES, Richmond C, Amor DJ, Boyce JO, Morgan AT, Hildebrand MS, Kaspi A, Bahlo M, Friðriksdóttir R, Katrínardóttir H, Sulem P, Stefánsson K, Björnsson HT, Mandelstam S, Morleo M, Mariani M; TUDP Study Group, Scala M, Accogli A, Torella A, Capra V, Wallis M, Jansen S, Weisfisz Q, de Haan H, Sadedin S; Broad Center for Mendelian Genomics, Lim SC, White SM, Ascher DB, Schenck A, Lockhart PJ, Christodoulou J, Tan TY
Am J Hum Genet 2022 Apr 7;109(4):601-617. doi: 10.1016/j.ajhg.2022.03.002. PMID: 35395208Free PMC Article
Nix JS, Blakeley J, Rodriguez FJ
Acta Neuropathol 2020 Apr;139(4):625-641. Epub 2019 Apr 8 doi: 10.1007/s00401-019-02002-2. PMID: 30963251Free PMC Article
Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmüller G, Chipaux M, Baulac S
Acta Neuropathol 2019 Dec;138(6):885-900. Epub 2019 Aug 23 doi: 10.1007/s00401-019-02061-5. PMID: 31444548Free PMC Article
O'Donnell-Luria AH, Pais LS, Faundes V, Wood JC, Sveden A, Luria V, Abou Jamra R, Accogli A, Amburgey K, Anderlid BM, Azzarello-Burri S, Basinger AA, Bianchini C, Bird LM, Buchert R, Carre W, Ceulemans S, Charles P, Cox H, Culliton L, Currò A; Deciphering Developmental Disorders (DDD) Study, Demurger F, Dowling JJ, Duban-Bedu B, Dubourg C, Eiset SE, Escobar LF, Ferrarini A, Haack TB, Hashim M, Heide S, Helbig KL, Helbig I, Heredia R, Héron D, Isidor B, Jonasson AR, Joset P, Keren B, Kok F, Kroes HY, Lavillaureix A, Lu X, Maas SM, Maegawa GHB, Marcelis CLM, Mark PR, Masruha MR, McLaughlin HM, McWalter K, Melchinger EU, Mercimek-Andrews S, Nava C, Pendziwiat M, Person R, Ramelli GP, Ramos LLP, Rauch A, Reavey C, Renieri A, Rieß A, Sanchez-Valle A, Sattar S, Saunders C, Schwarz N, Smol T, Srour M, Steindl K, Syrbe S, Taylor JC, Telegrafi A, Thiffault I, Trauner DA, van der Linden H Jr, van Koningsbruggen S, Villard L, Vogel I, Vogt J, Weber YG, Wentzensen IM, Widjaja E, Zak J, Baxter S, Banka S, Rodan LH
Am J Hum Genet 2019 Jun 6;104(6):1210-1222. Epub 2019 May 9 doi: 10.1016/j.ajhg.2019.03.021. PMID: 31079897Free PMC Article
Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K, Acero IH, Alkuraya FS, Arias P, Bernardini L, Bijlsma EK, Cole T, Coubes C, Dapia I, Davies S, Di Donato N, Elcioglu NH, Fahrner JA, Foster A, González NG, Huber I, Iascone M, Kaiser AS, Kamath A, Liebelt J, Lynch SA, Maas SM, Mammì C, Mathijssen IB, McKee S, Menke LA, Mirzaa GM, Montgomery T, Neubauer D, Neumann TE, Pintomalli L, Pisanti MA, Plomp AS, Price S, Salter C, Santos-Simarro F, Sarda P, Segovia M, Shaw-Smith C, Smithson S, Suri M, Valdez RM, Van Haeringen A, Van Hagen JM, Zollino M, Lapunzina P, Thakker RV, Zenker M, Hennekam RC
Hum Mutat 2018 Sep;39(9):1226-1237. Epub 2018 Jun 25 doi: 10.1002/humu.23563. PMID: 29897170Free PMC Article

Diagnosis

Nix JS, Blakeley J, Rodriguez FJ
Acta Neuropathol 2020 Apr;139(4):625-641. Epub 2019 Apr 8 doi: 10.1007/s00401-019-02002-2. PMID: 30963251Free PMC Article
Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmüller G, Chipaux M, Baulac S
Acta Neuropathol 2019 Dec;138(6):885-900. Epub 2019 Aug 23 doi: 10.1007/s00401-019-02061-5. PMID: 31444548Free PMC Article
Le Duc D, Giulivi C, Hiatt SM, Napoli E, Panoutsopoulos A, Harlan De Crescenzo A, Kotzaeridou U, Syrbe S, Anagnostou E, Azage M, Bend R, Begtrup A, Brown NJ, Büttner B, Cho MT, Cooper GM, Doering JH, Dubourg C, Everman DB, Hildebrand MS, Santos FJR, Kellam B, Keller-Ramey J, Lemke JR, Liu S, Niyazov D, Payne K, Person R, Quélin C, Schnur RE, Smith BT, Strober J, Walker S, Wallis M, Walsh L, Yang S, Yuen RKC, Ziegler A, Sticht H, Pride MC, Orosco L, Martínez-Cerdeño V, Silverman JL, Crawley JN, Scherer SW, Zarbalis KS, Jamra R
Brain 2019 Sep 1;142(9):2617-2630. doi: 10.1093/brain/awz198. PMID: 31327001Free PMC Article
Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K, Acero IH, Alkuraya FS, Arias P, Bernardini L, Bijlsma EK, Cole T, Coubes C, Dapia I, Davies S, Di Donato N, Elcioglu NH, Fahrner JA, Foster A, González NG, Huber I, Iascone M, Kaiser AS, Kamath A, Liebelt J, Lynch SA, Maas SM, Mammì C, Mathijssen IB, McKee S, Menke LA, Mirzaa GM, Montgomery T, Neubauer D, Neumann TE, Pintomalli L, Pisanti MA, Plomp AS, Price S, Salter C, Santos-Simarro F, Sarda P, Segovia M, Shaw-Smith C, Smithson S, Suri M, Valdez RM, Van Haeringen A, Van Hagen JM, Zollino M, Lapunzina P, Thakker RV, Zenker M, Hennekam RC
Hum Mutat 2018 Sep;39(9):1226-1237. Epub 2018 Jun 25 doi: 10.1002/humu.23563. PMID: 29897170Free PMC Article
Winden KD, Yuskaitis CJ, Poduri A
Semin Neurol 2015 Jun;35(3):277-87. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552622. PMID: 26060907

Therapy

Goel K, Ghadiyaram A, Krishnakumar A, Morden FTC, Higashihara TJ, Harris WB, Shlobin NA, Wang A, Karunungan K, Dubey A, Phillips HW, Weil AG, Fallah A
Neurosurgery 2024 Apr 1;94(4):666-678. Epub 2023 Nov 17 doi: 10.1227/neu.0000000000002759. PMID: 37975663
Goel K, Phillips HW, Chen JS, Ngo J, Edmonds B, Ha PX, Wang A, Weil A, Russell BE, Salamon N, Nariai H, Fallah A
Epilepsia 2024 Jan;65(1):57-72. Epub 2023 Nov 11 doi: 10.1111/epi.17807. PMID: 37873610
Bouchereau J, Schiff M
J Nutr 2020 Oct 1;150(Suppl 1):2556S-2560S. doi: 10.1093/jn/nxaa112. PMID: 33000154
Ostendorf AP, Wong M
CNS Drugs 2015 Feb;29(2):91-9. doi: 10.1007/s40263-014-0223-x. PMID: 25633849Free PMC Article
Galanopoulou AS, Gorter JA, Cepeda C
Epilepsia 2012 Jul;53(7):1119-30. Epub 2012 May 11 doi: 10.1111/j.1528-1167.2012.03506.x. PMID: 22578218Free PMC Article

Prognosis

Goel K, Ghadiyaram A, Krishnakumar A, Morden FTC, Higashihara TJ, Harris WB, Shlobin NA, Wang A, Karunungan K, Dubey A, Phillips HW, Weil AG, Fallah A
Neurosurgery 2024 Apr 1;94(4):666-678. Epub 2023 Nov 17 doi: 10.1227/neu.0000000000002759. PMID: 37975663
Goel K, Phillips HW, Chen JS, Ngo J, Edmonds B, Ha PX, Wang A, Weil A, Russell BE, Salamon N, Nariai H, Fallah A
Epilepsia 2024 Jan;65(1):57-72. Epub 2023 Nov 11 doi: 10.1111/epi.17807. PMID: 37873610
Boßelmann CM, Leu C, Lal D
Neurobiol Dis 2023 Aug;184:106208. Epub 2023 Jun 19 doi: 10.1016/j.nbd.2023.106208. PMID: 37343892
Stephenson SEM, Costain G, Blok LER, Silk MA, Nguyen TB, Dong X, Alhuzaimi DE, Dowling JJ, Walker S, Amburgey K, Hayeems RZ, Rodan LH, Schwartz MA, Picker J, Lynch SA, Gupta A, Rasmussen KJ, Schimmenti LA, Klee EW, Niu Z, Agre KE, Chilton I, Chung WK, Revah-Politi A, Au PYB, Griffith C, Racobaldo M, Raas-Rothschild A, Ben Zeev B, Barel O, Moutton S, Morice-Picard F, Carmignac V, Cornaton J, Marle N, Devinsky O, Stimach C, Wechsler SB, Hainline BE, Sapp K, Willems M, Bruel AL, Dias KR, Evans CA, Roscioli T, Sachdev R, Temple SEL, Zhu Y, Baker JJ, Scheffer IE, Gardiner FJ, Schneider AL, Muir AM, Mefford HC, Crunk A, Heise EM, Millan F, Monaghan KG, Person R, Rhodes L, Richards S, Wentzensen IM, Cogné B, Isidor B, Nizon M, Vincent M, Besnard T, Piton A, Marcelis C, Kato K, Koyama N, Ogi T, Goh ES, Richmond C, Amor DJ, Boyce JO, Morgan AT, Hildebrand MS, Kaspi A, Bahlo M, Friðriksdóttir R, Katrínardóttir H, Sulem P, Stefánsson K, Björnsson HT, Mandelstam S, Morleo M, Mariani M; TUDP Study Group, Scala M, Accogli A, Torella A, Capra V, Wallis M, Jansen S, Weisfisz Q, de Haan H, Sadedin S; Broad Center for Mendelian Genomics, Lim SC, White SM, Ascher DB, Schenck A, Lockhart PJ, Christodoulou J, Tan TY
Am J Hum Genet 2022 Apr 7;109(4):601-617. doi: 10.1016/j.ajhg.2022.03.002. PMID: 35395208Free PMC Article
Alotaibi F, Albaradie R, Almubarak S, Baeesa S, Steven DA, Girvin JP
Can J Neurol Sci 2021 Jul;48(4):451-463. Epub 2020 Oct 1 doi: 10.1017/cjn.2020.216. PMID: 32998781

Clinical prediction guides

Goel K, Phillips HW, Chen JS, Ngo J, Edmonds B, Ha PX, Wang A, Weil A, Russell BE, Salamon N, Nariai H, Fallah A
Epilepsia 2024 Jan;65(1):57-72. Epub 2023 Nov 11 doi: 10.1111/epi.17807. PMID: 37873610
Koop K, Yuan W, Tessadori F, Rodriguez-Polanco WR, Grubbs J, Zhang B, Osmond M, Graham G, Sawyer S, Conboy E, Vetrini F, Treat K, Płoski R, Pienkowski VM, Kłosowska A, Fieg E, Krier J, Mallebranche C, Alban Z, Aldinger KA, Ritter D, Macnamara E, Sullivan B, Herriges J, Alaimo JT, Helbig C, Ellis CA, van Eyk C, Gecz J, Farrugia D, Osei-Owusu I, Adès L, van den Boogaard MJ, Fuchs S, Bakker J, Duran K, Dawson ZD, Lindsey A, Huang H, Baldridge D, Silverman GA, Grant BD, Raizen D; Undiagnosed Diseases Network, van Haaften G, Pak SC, Rehmann H, Schedl T, van Hasselt P
Hum Mol Genet 2023 Oct 17;32(21):3063-3077. doi: 10.1093/hmg/ddad130. PMID: 37552066Free PMC Article
Stephenson SEM, Costain G, Blok LER, Silk MA, Nguyen TB, Dong X, Alhuzaimi DE, Dowling JJ, Walker S, Amburgey K, Hayeems RZ, Rodan LH, Schwartz MA, Picker J, Lynch SA, Gupta A, Rasmussen KJ, Schimmenti LA, Klee EW, Niu Z, Agre KE, Chilton I, Chung WK, Revah-Politi A, Au PYB, Griffith C, Racobaldo M, Raas-Rothschild A, Ben Zeev B, Barel O, Moutton S, Morice-Picard F, Carmignac V, Cornaton J, Marle N, Devinsky O, Stimach C, Wechsler SB, Hainline BE, Sapp K, Willems M, Bruel AL, Dias KR, Evans CA, Roscioli T, Sachdev R, Temple SEL, Zhu Y, Baker JJ, Scheffer IE, Gardiner FJ, Schneider AL, Muir AM, Mefford HC, Crunk A, Heise EM, Millan F, Monaghan KG, Person R, Rhodes L, Richards S, Wentzensen IM, Cogné B, Isidor B, Nizon M, Vincent M, Besnard T, Piton A, Marcelis C, Kato K, Koyama N, Ogi T, Goh ES, Richmond C, Amor DJ, Boyce JO, Morgan AT, Hildebrand MS, Kaspi A, Bahlo M, Friðriksdóttir R, Katrínardóttir H, Sulem P, Stefánsson K, Björnsson HT, Mandelstam S, Morleo M, Mariani M; TUDP Study Group, Scala M, Accogli A, Torella A, Capra V, Wallis M, Jansen S, Weisfisz Q, de Haan H, Sadedin S; Broad Center for Mendelian Genomics, Lim SC, White SM, Ascher DB, Schenck A, Lockhart PJ, Christodoulou J, Tan TY
Am J Hum Genet 2022 Apr 7;109(4):601-617. doi: 10.1016/j.ajhg.2022.03.002. PMID: 35395208Free PMC Article
Alotaibi F, Albaradie R, Almubarak S, Baeesa S, Steven DA, Girvin JP
Can J Neurol Sci 2021 Jul;48(4):451-463. Epub 2020 Oct 1 doi: 10.1017/cjn.2020.216. PMID: 32998781
Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C, Dorison N, Fohlen M, Polivka M, Weckhuysen S, Dorfmüller G, Chipaux M, Baulac S
Acta Neuropathol 2019 Dec;138(6):885-900. Epub 2019 Aug 23 doi: 10.1007/s00401-019-02061-5. PMID: 31444548Free PMC Article

Recent systematic reviews

Pan PY, Bölte S, Kaur P, Jamil S, Jonsson U
Autism 2021 Apr;25(3):812-830. Epub 2020 Sep 9 doi: 10.1177/1362361320951370. PMID: 32907344

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