Phenytoin (dilantin)-induced cleft lip and palate in A/J mice: a scanning and transmission electron microscopic study.

High incidences of cleft lip and palate (CLP) produced by maternal intraperitoneal administration of 75 mg/kg phenytoin on gestational day 10 to A/J mice are associated with a severe size reduction in the lateral nasal process. Scanning and transmission EM analyses of this region demonstrate a marked change in the morphology of the mesenchymal cells underlying the surface epithelium in treated versus control day 11 (7-tail somite) embryos: long, branching cellular processes, which form a dense meshwork that appears to interact with the epithelial basement lamina in control embryos are undeveloped or absent in phenytoin-treated embryos. The ultrastructural morphology of these cell processes is described and their possible importance in normal development is discussed. Scanning EM observations of incomplete clefts of the lip which frequently result from phenytoin treatment indicate that Simonart's bands form from fusion of the lateral and medial nasal processes in association with a lack of fusion of the maxillary process with the medial nasal process.