Mouse fetal hydantoin syndrome: effects of maternal seizures.

To test the effect of maternal seizure disorders on prenatal structural development, the mouse neurological mutant quaking (qk) was used. Administering phenytoin in the drinking water of females homozygous for the quaking allele reduced the frequency of tonic-clonic seizures typical for this mutant from a background rate of 2.06 to 0.34 seizures per mouse day. As the seizure frequency decreased, the percentage of fetuses exhibiting abnormalities associated with the mouse fetal hydantoin syndrome increased from 0 to 77. As in previous studies with the mouse syndrome, the increase in malformations was associated with increased maternal serum phenytoin levels. The results of this study indicate that the maternal serum phenytoin level, and not the maternal seizure disorder, is the etiologic agent responsible for the malformations observed in this syndrome.