Abstracts

RATIONALE: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a recently described idiopathic localization-related epilepsy syndrome characterized by auditory and visual ictal symptoms. ADPEAF is a rare syndrome, thus far described in fewer than a dozen families. ADPEAF was mapped to chromosome 10q24, and is caused by mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene. We describe the clinical characteristics and molecular studies in a new, large, multigenerational Italian-American family with partial epilepsy with auditory features.
METHODS: Clinical study: Our family consisted of 36 individuals in five generations. Nine had a history of partial epilepsy. Seven affected members agreed to participate after informed consent. They underwent a semi-structured interview focusing on seizure semiology and seizure-precipitating factors, and neurological examination. Their medical records were reviewed, including EEG records and brain imaging studies when available. We collected eight blood samples, seven were from affected family members. Genetic studies: Exon spanning primers were designed for each of the eight exons of LGI1. Each exon was amplified by polymerase chain reaction using the genomic DNA of an affected individual. The product was purified and screened for mutations by automated cycle sequencing.
RESULTS: All seven affected individuals had an auditory aura. The mean age of onset was 25 years (range 8-42). Two of the affected individuals reported visual auras. Complex partial seizures occurred in two subjects. All patients had generalized tonic-clonic seizures. All affected individuals had normal neurologic examinations. Neuroimaging was normal except magnetic resonance imaging in the proband showed symmetric, bilateral T2 and FLAIR signal abnormalities in the medial basal ganglia. EEGs in five affected individuals were normal, the proband[ssquote]s EEG showed left anterior temporal epileptiform features. Genetic studies: The partial epilepsy segregated as an autosomal dominant trait with reduced penetrance. LGI1 mutation screening is in progress.
CONCLUSIONS: ADPEAF is a rare syndrome. As more families are described, the clinical, electrophysiological, and genetic characteristics will be better defined. ADPEAF can arise from haploinsufficiency of LGI1, a gene previously known to play a role in progression of glial tumors. However, mutations have been demonstrated thus far in 5 families. Whether ADPEAF is genetically heterogeneous is yet to be determined by further studies of large families with this epilepsy syndrome.
[Supported by: Paul Beeson Physician Faculty Award and the Hellman Family Foundation (F.M.H.)]