Impaired cognitive function in idiopathic generalized epilepsy and unaffected family members: An epilepsy endophenotype

Objective Idiopathic generalized epilepsy (IGE) has a strong genetic component, and patients with IGE show deficits in a range of frontal lobe functions. Previous studies provide hints that unaffected siblings of people with IGE may share some of these cognitive deficits, suggesting that these deficits may be genetically determined endophenotypes. Establishment of a neurocognitive endophenotype of IGE would contribute to genetic studies and increase our understanding of the pathophysiology of IGE. To identify potential neurocognitive endophenotypes of IGE, this study aimed to measure neuropsychological performance in patients with IGE, their unaffected relatives, and healthy controls. Methods Thirty-six patients with IGE, 38 first-degree relatives, and 40 healthy controls were examined using a battery of neuropsychological tests sensitive to frontal lobe dysfunction (executive function, nonverbal reasoning, verbal generativity, response inhibition, attention, and working memory). Subject groups were compared using robust Bonferroni-corrected statistics. Results Patients with IGE showed deficits in nonverbal reasoning, verbal generativity, attention, and working memory. Relatives exhibited a parallel profile of cognitive abilities, with significant deficits in these tasks. Patients tended to show greater impairment than relatives in these tasks. Significance This study shows that measures of nonverbal reasoning, verbal generativity, sustained attention, and working memory are endophenotypes of IGE and offer the potential for aiding molecular genetic studies and elucidating the pathophysiology of IGE. Patients tended to demonstrate greater impairment in these tasks, possibly because of a greater genetic contribution and/or disease-related factors.