Abstracts

Rationale: Lennox-Gastaut Syndrome (LGS) is a severe childhood-onset epilepsy syndrome characterized by mental retardation, multiple seizure types and characteristic EEG features. Symptomatic LGS (sLGS) is caused by structural lesions such as malformations of cortical development or acquired brain insults. Cryptogenic LGS (cLGS) constitutes ~25% of cases and may have a stronger genetic basis. cLGS is less likely than symptomatic LGS to evolve from Infantile Spasms.Methods: The Epilepsy Phenome/Genome Project (EPGP) is a multi-center collaborative effort to collect detailed phenotypic and genetic data on a large number of epilepsy patients, including cLGS. Detailed standardized phenotypic data was collected from 147 patients with cLGS and their parents across 19 centers in the USA and Australia. Results: The median age at enrollment was 13 years (range 2-51) and 64% were male. All patients had developmental delay; however, only 25.2% of patients had developmental delay prior to the onset of seizures. 22.6% of the adult patients had completed high school. The median age at first seizure was 1 year (range 0-12). 13.4% of patients had febrile seizures, of which 25% were complex. The neurological examination was abnormal within 3 months of seizure onset in 20.6%, with usually a non-focal finding such as hypotonia or speech delay. 27.8% of patients had any family history of epilepsy, and 5.4% had a first degree relative with epilepsy. The average age of their parents at birth was 31 years (maternal average 30 years, paternal average 32 years). 9.3% of patients evolved from West syndrome (Infantile Spasms). The most common seizure types were atypical absence (68.7%), atonic (63.5%), generalized tonic-clonic (60.4%) and tonic seizures (52%). Other seizure types included myoclonic (50%), partial (23.8%), and nonconvulsive seizures (6.2%). The mean posterior dominant occipital rhythm was 6.8Hz (SD 1.9). 23 patients had a normal age-matched posterior dominant rhythm (35.9%). 96% of patients had generalized abnormalities. Median generalized burst frequency was 2 (range 1-5), while 8 patients had predominantly generalized fast discharges (12-25Hz). 20.5% of patients had focal slowing and 51.9% had focal sharp waves. Conclusions: Lennox-Gastaut syndrome is a developmentally devastating neurological illness. Developmental delay often follows the onset of seizures. This may represent a window of opportunity to reduce delay by rapid and aggressive seizure control. The association with familial epilepsy and febrile seizures suggest a genetic influence. Further analysis of collected genetic material with these phenotypic characteristics will provide further insight.