A NEW IN-UTERO MODEL FOR LATERAL FACIAL CLEFTS

The etiopathogenesis behind the formation of atypical craniofacial fac ial clefts remains unknown. To test the hypothesis that physical restr icting forces such as amniotic bands can lead to the formation of thes e unusual clefts in the postorganogenesis period, we have modified a p reviously reported fetal lamb model of amniotic band syndrome to exami ne the effects of these bands on craniofacial development. Five 70-day gestation fetal lambs (term, 140 days) were exposed via a maternal hy sterotomy. In each animal, an attempt was made to create a lateral cra niofacial cleft by applying a 2-O nylon suture as a constriction band to the growing face. The sutures were attached to either the zygomatic arch or the infraorbital rim externally and then looped circumferenti ally into the oral commissure. Each suture was positioned so as to cre ate either a Tessier type 5 or a Tessier type 7 cleft. Four of five fe tal lambs survived to term. Both types of lateral facial clefts were e ffectively produced using this model. In each group, the presence of a n intraoral constriction band led to the formation of macrostomia, wit h an average 7.4-mm lateral displacement of the oral commissure. In ad dition to these soft tissue changes, each animal also had partial bony clefting (i.e., a bony groove) induced by the pressure of the restric tion band across the growing facial skeleton. In the two lambs with th e Tessier type 7 cleft, incomplete bony clefts developed across the zy gomatic arch. In three animals with bands placed across the medial inf raorbital rim, significant infraorbital and malar bony clefts formed s imilar to a classic Tessier type 5 facial cleft. No evidence of tissue necrosis, maceration, or ulceration was noted in any animal. These da ta present, for the first time, evidence that the constriction of cran iofacial growth by external forces such as a swallowed amnionic band c an lead to the development of lateral facial clefting involving both s oft tissue and bony elements. These malformations are likely due to a combination of directly tethering normal tissue migration and an incre ase in local pressure, which produces cellular ischemia and apoptosis. Furthermore, our data demonstrate that these clefts can occur later i n fetal development during a period of facial growth rather than durin g the period of primary facial morphogenesis.