Twelve monozygotic twins, discordant for epilepsy, were analysed for nonhereditary etiological factors by clinical history, MRI, and quantitative brain volume studies at the Brain Research Institute, University of Melbourne, Victoria, Australia. A major acquired factor explained discordance in 4 of 12 affected twins. All had temporal lobe epilepsy, 2 twins had a prolonged febrile convulsion in early childhood and hippocampal sclerosis on MRI, and 2 had a pre- or perinatal ischemic-hypoxic insult with ischemic lesions. MRI showed significant cortical maldevelopment (MCD) in 4 of the remaining 8 affected MZ twins without major acquired risk factors. In the remaining 4 twin pairs with discordant seizures unexplained by major acquired factors or MCDs, 2 twin pairs had differences in quantitative MRI brain volumes, indicative of subtle maldevelopment and a nonhereditary etiology. Both affected twins had idiopathic generalized epilepsy and larger hippocampal and intracranial volumes than the unaffected co-twins. No reason for discordance was uncovered in 2 or 12 twins. 
COMMENT. Discordance for epilepsy in monozygous twin pairs is explained by noninherited factors. These include major acquired clinical risk factors, malformation of cortical development demonstrated by MRI, and quantitative brain volume changes. Idiopathic generalized epilepsy, usually considered primarily genetic in etiology, may be caused by underlying subtle developmental abnormalities. Occult acquired factors may explain cases of cryptogenic epilepsy.