Lennox-Gastaut syndrome of unknown cause: phenotypic characteristics of patients in the Epilepsy Phenome/Genome Project

Epilepsia. 2013 Nov;54(11):1898-904. doi: 10.1111/epi.12395. Epub 2013 Oct 7.

Abstract

Purpose: Lennox-Gastaut syndrome (LGS) is a devastating childhood-onset epilepsy syndrome. The cause is unknown in 25% of cases. Little has been described about the specific clinical or electroencephalography (EEG) features of LGS of unknown or genetic cause (LGS(u)). The Epilepsy Phenome/Genome Project (EPGP) aims to characterize LGS(u) by phenotypic analysis of patients with LGS(u) and their parents.

Methods: One hundred thirty-five patients with LGS with no known etiology and their parents were enrolled from 19 EPGP centers in the United States and Australia. Clinical data from medical records, standardized questionnaires, imaging, and EEG were collected with use of online informatics systems developed for EPGP.

Key findings: LGS(u) in the EPGP cohort had a broad range of onset of epilepsy from 1 to 13 years, was male predominant (p < 0.0002), and was associated with normal development prior to seizure onset in 59.2% of patients. Despite the diagnosis, almost half of the adult patients with LGS(u) completed secondary school. Parents were cognitively normal. All subjects had EEG recordings with generalized epileptiform abnormalities with a spike wave frequency range of 1-5 Hz (median 2 Hz), whereas 8.1% of subjects had EEG studies with a normal posterior dominant rhythm. Almost 12% of patients evolved from West syndrome.

Significance: LGS(u) has distinctive characteristics including a broad age range of onset, male predominance, and often normal development prior to the onset of seizures. Cognitive achievements such as completion of secondary school were possible in half of adult patients. Our phenotypic description of LGS(u) coupled with future genetic studies will advance our understanding of this epilepsy syndrome.

Keywords: Epilepsy; Epilepsy Phenome/Genome Project; Lennox-Gastaut; Phenotype; Slow spike wave; Unknown.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Australia
  • Child
  • Child, Preschool
  • Electroencephalography / methods
  • Female
  • Genome, Human
  • Genotype
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Lennox Gastaut Syndrome
  • Male
  • Middle Aged
  • Parents
  • Phenotype
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology
  • Syndrome
  • United States
  • Young Adult

Supplementary concepts

  • Epileptic encephalopathy, Lennox-Gastaut type