The Fetal Cleft Palate: I. Characterization of a Congenital Model

Any animal model of a human congenital anomaly established by iatrogenic methods involving intrauterine fetal manipulation has limited clinical applicability. A congenital model that more closely simulates the etiopathogenesis of a human anomaly may provide data that can more readily be extrapolated to that anomaly and, therefore, be used in diagnostic and management strategies. The present work provides a description and characterization of a congenital model of cleft palate in the goat. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Sixteen pregnant goats were gavaged twice daily during gestational days 32 through 41 [term, 145 days] with a plant slurry of Nicotiana glauca containing the piperidine alkaloid teratogen anabasine. Gross analysis and measurement of fetal clefts were performed at 60, 70, and 85 days gestation (four fetuses were studied at each time point). Seventeen clefted kids were sacrificed at specific intervals after birth (2 weeks, and 1, 3, and 6 months); after skull debridement and preparation, they were compared with 12 unclefted control kids. Complete clefting of the secondary palate occurred in 97 percent of the fetuses. In all cases, the cleft extended from the posterior aspect of the alveolar ridge to the uvula; the majority of these clefts were bilateral, with complete detachment of the vomer. Morphologically, these clefts were similar to human clefts. Eighteen percent of clefted newborn kids demonstrated gross maxillary hypoplasia and midfacial retrusion at birth with a relative Class III malocclusion. Direct measurement of the congenital caprine skulls confirmed these findings. The incidence of midfacial growth abnormalities in these clefted animals raises questions regarding the etiopathogenesis of facial dysmorphology that is unrelated to scarring of the maxilla. This congenital cleft palate model is currently being used to explore these questions and others related to craniofacial growth and palatal function after in utero repair.