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

• Published in: Epilepsia (Copenhagen) Vol. 54; no. 11; pp. 1898 - 1904
• Main Authors: Widdess‐Walsh, Peter, Dlugos, Dennis, Fahlstrom, Robyn, Joshi, Sucheta, Shellhaas, Renée, Boro, Alex, Sullivan, Joseph, Geller, Eric
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2013
• Subjects: Adolescent; Adult; Age; Age of Onset; Australia; Child; Child, Preschool; Electroencephalography - methods; Epilepsy; Epilepsy Phenome/Genome Project; Female; Genome, Human; Genotype; Humans; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Lennox Gastaut Syndrome; Lennox‐Gastaut; Male; Middle Aged; Parents; Phenotype; Slow spike wave; Spasms, Infantile - genetics; Spasms, Infantile - physiopathology; Syndrome; United States; Unknown; Young Adult; Australia; United States; Phenotype; Unknown; Lennox-Gastaut; Slow spike wave; Epilepsy; Epilepsy Phenome/Genome Project
• ISSN: 0013-9580; 1528-1167; 1528-1167
• DOI: 10.1111/epi.12395

Summary 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 (LGSu). The Epilepsy Phenome/Genome Project (EPGP) aims to characterize LGSu by phenotypic analysis of patients with LGSu 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 LGSu 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 LGSu 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 LGSu 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 LGSu coupled with future genetic studies will advance our understanding of this epilepsy syndrome.