Chromosome fragile sites in mentally retarded males: increased incidence with seizures and diphenylhydantoin therapy

Chromosome fragile site or lesion data were examined in 154 institutionalized mentally retarded males with or without seizures or treated with anti-seizure medication. Blood lymphocytes were cultured using three different cell culture conditions and the incidence of specific chromosome fragile sites (10q25, 16q22, and 12q23) or lesions determined. Increased fragile sites were seen in mentally retarded males with seizures compared to those without seizures in cells grown in folate-deplete Medium 199. Those with seizures and treated with diphenylhydantoin had a higher incidence of induced fragile sites (p < 0.001) relative to similar patients treated with anti-seizure medication other than diphenylhydantoin. These results suggest that a cohort of patients with mental retardation and seizures are more likely to have induced cytogenetic changes when treated with diphenylhydantoin than mentally retarded individuals without seizures.