Lennox-Gastaut Syndrome

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/lennox-gastaut-syndrome

Lennox-Gastaut syndrome is a severe condition characterized by recurrent seizures (epilepsy) that begin early in life.

genetic conditions

1. Introduction

Affected Lennox-Gastaut syndrome individuals have multiple types of seizures, a particular pattern of brain activity (called slow spike-and-wave) measured by a test called an electroencephalogram (EEG), and impaired mental abilities.

In 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 and cause sudden falls. Also common are atypical absence seizures, which cause a very brief partial or complete loss of consciousness. Additionally, many affected individuals have episodes called drop attacks, which cause sudden falls that can result in serious or life-threatening injuries. Drop attacks may be caused by sudden loss of muscle tone (described as atonic) or by abnormal muscle contraction (described as tonic). 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.

Most children with Lennox-Gastaut syndrome have intellectual disability or learning problems even before seizures begin. These problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems. Many also have delayed development of 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 the usual activities of daily living. However, a small percentage of affected adults 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 and injuries from falls.

2. Frequency

Lennox-Gastaut syndrome affects an estimated 1 to 2 per million people. This condition accounts for less than 5 percent of all cases of childhood epilepsy. For unknown reasons, it appears to be more common in males than in females.

3. Causes

Lennox-Gastaut syndrome can have many different causes. The disorder likely has a genetic component, although the specific genetic factors are not well understood.

Most cases of Lennox-Gastaut syndrome are caused by an existing neurological abnormality. These cases can be associated with brain injuries that occur before or during birth, problems with blood flow in the developing brain, brain infections, or other disorders affecting the nervous system. The condition can also result from brain malformations such as forms of cortical dysplasia, which are abnormalities in the outer surface of the brain (cerebral cortex). Many people with Lennox-Gastaut syndrome have a history of epilepsy beginning in infancy (infantile spasms) or a related condition called West syndrome before developing the features of Lennox-Gastaut syndrome.

In addition, mutations in several genes have been associated with Lennox-Gastaut syndrome, each in a small number of affected individuals. These genes are involved in the function of nerve cells in the brain, but it is unclear how changes in them contribute to the development of Lennox-Gastaut syndrome. The condition can also occur as part of a genetic disorder such as tuberous sclerosis complex.

In about 10 percent of affected individuals, the cause of Lennox-Gastaut syndrome is unknown. These individuals have no history of seizures, neurological problems, or delayed development.

4. Inheritance

Most cases of Lennox-Gastaut syndrome are sporadic, which means they occur in people with no history of the disorder in their family. When Lennox-Gastaut syndrome is associated with a genetic change, the mutation is usually not inherited but occurs as a random (de novo) event during the formation of reproductive cells (eggs or sperm) in an affected person's parent or in early embryonic development. However, 3 to 30 percent of people with this condition have a family history of some type of epilepsy, indicating that inherited genetic factors may play a role in some cases of Lennox-Gastaut syndrome.

5. Other Names for This Condition

childhood epileptic encephalopathy with diffuse slow spikes and waves
LGS

References

Arzimanoglou A, French J, Blume WT, Cross JH, Ernst JP, Feucht M, Genton P,Guerrini R, Kluger G, Pellock JM, Perucca E, Wheless JW. Lennox-Gastaut syndrome:a consensus approach on diagnosis, assessment, management, and trial methodology.Lancet Neurol. 2009 Jan;8(1):82-93. doi: 10.1016/S1474-4422(08)70292-8. Review.
Autry AR, Trevathan E, Van Naarden Braun K, Yeargin-Allsopp M. Increased risk of death among children with Lennox-Gastaut syndrome and infantile spasms. JChild Neurol. 2010 Apr;25(4):441-7. doi: 10.1177/0883073809348355.
Camfield PR. Definition and natural history of Lennox-Gastaut syndrome.Epilepsia. 2011 Aug;52 Suppl 5:3-9. doi: 10.1111/j.1528-1167.2011.03177.x.
Cross JH, Auvin S, Falip M, Striano P, Arzimanoglou A. Expert Opinion on theManagement of Lennox-Gastaut Syndrome: Treatment Algorithms and PracticalConsiderations. Front Neurol. 2017 Sep 29;8:505. doi: 10.3389/fneur.2017.00505.
Epi4K Consortium; Epilepsy Phenome/Genome Project, 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-KhalilB, 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. De novo mutations in epilepticencephalopathies. Nature. 2013 Sep 12;501(7466):217-21. doi: 10.1038/nature12439.
EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4KConsortium. De novo mutations in synaptic transmission genes including DNM1 causeepileptic encephalopathies. Am J Hum Genet. 2014 Oct 2;95(4):360-70. doi:10.1016/j.ajhg.2014.08.013.Jan 5;100(1):179.
Hancock EC, Cross HH. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD003277. doi: 10.1002/14651858.CD003277.pub2. Review.Update in: Cochrane Database Syst Rev. 2013;2:CD003277.
Hancock EC, Cross JH. Treatment of Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD003277. doi: 10.1002/14651858.CD003277.pub3. Review.
Lund C, Brodtkorb E, Øye AM, Røsby O, Selmer KK. CHD2 mutations inLennox-Gastaut syndrome. Epilepsy Behav. 2014 Apr;33:18-21. doi:10.1016/j.yebeh.2014.02.005.
McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 2016Mar;15(3):304-16. doi: 10.1016/S1474-4422(15)00250-1.
Nakashima M, Kouga T, Lourenço CM, Shiina M, Goto T, Tsurusaki Y, Miyatake S, Miyake N, Saitsu H, Ogata K, Osaka H, Matsumoto N. De novo DNM1 mutations in two cases of epileptic encephalopathy. Epilepsia. 2016 Jan;57(1):e18-23. doi:10.1111/epi.13257.
Ostendorf AP, Ng YT. Treatment-resistant Lennox-Gastaut syndrome: therapeutic trends, challenges and future directions. Neuropsychiatr Dis Treat. 2017 Apr20;13:1131-1140. doi: 10.2147/NDT.S115996.
Selmer KK, Lund C, Brandal K, Undlien DE, Brodtkorb E. SCN1A mutationscreening in adult patients with Lennox-Gastaut syndrome features. EpilepsyBehav. 2009 Nov;16(3):555-7. doi: 10.1016/j.yebeh.2009.08.021.
Terrone G, Bienvenu T, Germanaud D, Barthez-Carpentier MA, Diebold B, Delanoe C, Passemard S, Auvin S. A case of Lennox-Gastaut syndrome in a patient withFOXG1-related disorder. Epilepsia. 2014 Nov;55(11):e116-9. doi:10.1111/epi.12800.
Trevathan E. Infantile spasms and Lennox-Gastaut syndrome. J Child Neurol.2002 Feb;17 Suppl 2:2S9-2S22. Review. Erratum in: J Child Neurol. 2003May;18(5):374.
Zhou P, He N, Zhang JW, Lin ZJ, Wang J, Yan LM, Meng H, Tang B, Li BM, Liu XR,Shi YW, Zhai QX, Yi YH, Liao WP. Novel mutations and phenotypes ofepilepsy-associated genes in epileptic encephalopathies. Genes Brain Behav. 2018 Nov;17(8):e12456. doi: 10.1111/gbb.12456.

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Camila Xu

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Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The genes associated with Lennox-Gastaut syndrome

4. Inheritance

5. Other Names for This Condition

References