The interrelationship of genetics and prenatal injury in the genesis of malformations of cortical development (MCD) was studied at the University of Campinas, SP, Brazil. In a series of 76 consecutive patients with MCD, 21 (28%) had focal cortical dysplasia, 19 (25%) had heterotopias or agyria-pachygyria, and 36 (47%) had polymicrogyria or schizencephaly. In the group with heterotopias, 6 (32%) had a family history of MCD, mental retardation, or miscarriages, suggesting a genetic factor in etiology. In the group with polymicrogyria, 5 (14%) had a family history of MCD. Prenatal events had occurred in 28 (37%) of the total series and only 2 of controls (5%); they were significantly more frequent in the patients with heterotopias and polymicrogyria (P<.001). Epilepsy occurred in all patients with focal cortical dysplasia, in 89% of the heterotopia group, and less frequently (P<.001) in patients with polymicrogyria (47%). Epilepsy associated with polymicrogyria was more easily controlled than in other forms of MCD. [1]

COMMENT. The variable clinical manifestations encountered with different forms of MCD are determined by a combination of genetic and prenatal factors. The more frequent and severe epilepsy associated with focal cortical dysplasia is less frequently related to genetic and prenatal factors, whereas the less frequent and milder epilepsy common to the polymicrogyria group has a stronger association with genetic and prenatal events. Heterotopias are frequently linked to genetic predisposition.