Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut syndrome (LGS) is a rare, severe epileptic encephalopathy that most commonly affects children between the ages of 3 and 5 years.¹ LGS accounts for 2% to 5% of all cases of childhood epilepsy and approximately 10% of cases of epilepsy occurring before the age of 5 years.²

Initial Reports of LGS in the Medical Literature

Dr. Henri Jean Pascal Gastaut, a French neurologist and neuroanatomist who taught anatomical pathology at the University of Marseille, first described LGS in 1966, when he was director of the regional center for children with epilepsy.^2,3 

The document that Gastaut and colleagues published in Epilepsia in 1966 described LGS as a severe form of childhood epilepsy that was refractory to the antiepileptic treatments then available. Gastaut and colleagues were the first to identify and document the hallmark features of the condition, including^1,4:

• Frequent generalized epileptic seizures — most commonly tonic or absence seizures;
• Severe cognitive impairment; and
• Specific electroencephalographic (EEG) patterns consisting of interictal discharges of diffuse slow spike-waves pseudo-rhythmically repeated at 1.5 to 2.5 cycles per second.

Read more about LGS clinical features

Before the research of Gastaut and colleagues, Dr. William G. Lennox, an American neurologist and epileptologist, had independently studied the same characteristic EEG patterns in children with the syndrome. He described his findings in a research paper published in 1950 in Pediatrics, the journal of the American Academy of Pediatrics.^2,5 

Lennox first called the syndrome “petit mal variant.” In their 1966 document that further identified LGS, Gastaut and colleagues attributed discovery of the syndrome to Lennox, renaming it with the eponym “Lennox syndrome.”⁶ The condition eventually became known as Lennox-Gastaut syndrome. It is classified as one of the 8 syndromes under epileptic encephalopathy and can lead to a progressive decline of cognition and cerebral function, along with behavioral regression due to epileptogenic activity during brain maturation.⁶

Read more about LGS prognosis

History of LGS Etiology

Following the publications of Lennox and Gastaut, researchers focused their efforts on determining the etiology of the condition. LGS is subdivided into 2 categories: identifiable/secondary LGS and unknown/cryptogenic LGS.^2,6,7 

In approximately 65% to 75% of patients with LGS, the etiology can be identified as genetic, metabolic, or structural. Identifiable etiologies include tuberous sclerosis complex, congenital central nervous system infections, brain damage, or perinatal complications.  In the remaining 25% to 35% of cases, the cause is unknown.^6,7

Read more about LGS etiology

One identified etiology is the transformation of West syndrome into LGS. In 1976, a group of Japanese physicians and researchers – Shunsuke Ohtahara, Yoko Ohtsuka, and Yasuko Yamatogi – published a paper in Psychiatry and Clinical Neurosciences in which they described a connection between LGS and West syndrome.⁸ They observed a transition from West syndrome to LGS as EEG patterns changed with time.⁹ Following 30 years of study, Ohtahara and colleagues described a possible aged-related evolution from Ohtahara syndrome to West syndrome to LGS, with distinguishing EEG changes.¹⁰

Read more about LGS differential diagnosis

Recent Studies of Genetics in LGS

With technological advancements in the fields of genetics and genomics, research in the 21st century has focused on possible genetic factors contributing to the development of LGS. De novo mutations have been identified in certain genes that may account for some cases of LGS without a known cause.²

In 2021, researchers in Korea identified at least 14 possible genetic mutations associated with LGS.¹¹  Also in 2021, researchers used whole-genome sequencing to identify potential genetic causes of unexplained developmental and epileptic encephalopathies, including LGS. In particular, they detected tandem repeat expansions in both the coding and noncoding parts of the human genome in several patients with LGS of unknown etiology.¹²

Read more about LGS genetics

References

1. Camfield PR. Definition and natural history of Lennox-Gastaut syndrome. Epilepsia. 2011;52(s5):3-9. doi:10.1111/j.1528-1167.2011.03177.x
2. Amrutkar C, Riel-Romero RM. Lennox Gastaut syndrome. StatPearls [Internet]. Updated August 1, 2022. Accessed February 4, 2023. 
3. Henri Jean Pascal Gastaut. Whonamedit? Accessed February 4, 2023.
4. Gastaut H, Roger J, Soulayrol R, et al. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia. 1966;7(2):139-179. doi:10.1111/j.1528-1167.1966.tb06263.x
5. Lennox WG, Davis JP. Clinical correlates of the fast and the slow spike-wave electroencephalogram. Pediatrics. 1950;5(4):626-644. doi:10.1542/peds.5.4.626
6. Jahngir MU, Ahmad MQ, Jahangir M. Lennox-Gastaut syndrome: in a nutshell. Cureus. 10(8):e3134. doi:10.7759/cureus.3134
7. Asadi-Pooya AA. Lennox-Gastaut syndrome: a comprehensive review. Neurol Sci. 2018;39(3):403-414. doi:10.1007/s10072-017-3188-y
8. Ohtahara S, Yamatogi Y, Ohtsuka Y. Prognosis of the Lennox syndrome—long-term clinical and electroencephalographic follow-up study, especially with special reference to relationship with the West syndrome. Psychiatry Clin Neurosci. 1976;30(3):275-287. doi:10.1111/j.1440-1819.1976.tb02264.x
9. Ohtahara S, Ohtsuka Y, Yamatogi Y, Oka E. The early-infantile epileptic encephalopathy with suppression-burst: developmental aspects. Brain Dev. 1987;9(4):371-376. doi:10.1016/S0387-7604(87)80110-9
10. Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res. 2006;70 Suppl 1:S58-S67. doi:10.1016/j.eplepsyres.2005.11.021
11. Yang JO, Choi MH, Yoon JY, et al. Characteristics of genetic variations associated with Lennox-Gastaut syndrome in Korean families. Front Genet. 2021;11:590924. doi:10.3389/fgene.2020.590924
12. Qaiser F, Sadoway T, Yin Y, et al. Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox–Gastaut syndrome. Brain Commun. 2021;3(3):fcab207. doi:10.1093/braincomms/fcab207

Reviewed by Debjyoti Talukdar, MD, on 2/27/2023.

---

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.