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The Fetal Cleft Palate: V. Elucidation of the Mechanism of Palatal Clefting in the Congenital Caprine Model

Weinzweig, Jeffrey M.D.; Panter, Kip E. Ph.D.; Patel, Jagruti M.D.; Smith, Darren M. M.D.; Spangenberger, Anthony B.S.; Freeman, M Brandon M.D., Ph.D.

Plastic & Reconstructive Surgery:
doi: 10.1097/01.prs.0000302460.90076.96
Pediatric/Craniofacial: Original Articles
Abstract

Background: Failure of palatal shelf fusion at the precise gestational time point when shelf elevation and migration normally occur results in clefting. The present study defined the mechanism of clefting in the congenital caprine model by evaluating the temporal sequence of palatal shelf fusion.

Methods: Six Spanish-type goats pregnant with twins were gavaged for 10 days (gestational days 32 to 41) with anabasine. Goats were examined with ultrasound throughout this period to assess fetal movement and evaluated histologically. Twelve untreated, unclefted fetuses served as controls.

Results: After anabasine induction, real-time ultrasound confirmed a dramatic decrease in fetal movement. Hyperflexion of the neck occurred throughout the experimental period compared with control fetuses, in which spontaneous neck movements occurred. Histologic evaluation of the induced fetuses demonstrated the tongue wedged between the palatal shelves throughout the period of fusion. The shelves remained vertically oriented without elevation, ultimately resulting in clefting. The unclefted, control group demonstrated progressive elevation and migration of the palatal shelves between gestational days 38 and 40, with contact and fusion of the medial edge epithelia in the midline.

Conclusions: Palatal clefting in the congenital caprine model occurred concomitant with reduced fetal movement. Resultant neck hyperflexion causes the tongue to obstruct medial migration of the palatal shelves and fusion, whereas the shelves themselves are either directly prevented from elevation secondary to anabasine impairment or indirectly secondary to the obstructing tongue. Although the molecular mechanism for the teratogenic effects of anabasine remains elusive, the authors have demonstrated an association between reduced fetal movement and palatal clefting in their congenital caprine model.

Author Information

Burlington and Beverly, Mass.; Logan, Utah; and Providence, R.I.

From the Department of Plastic Surgery, Lahey Clinic Medical Center; U.S. Department of Agriculture, Agricultural Research Service, Poisonous Plant Research Laboratory; Department of Plastic Surgery, Beverly Hospital; and Department of Plastic Surgery, Rhode Island Hospital, Brown University.

Received for publication November 13, 2006; accepted April 19, 2007.

Presented in part at the 40th Annual Plastic Surgery Senior Residents’ Conference, in Providence, Rhode Island, March 28 through April 1, 2001 (recipient of the Lyndon Peer, M.D., best paper award, congenital category); the Ninth International Congress of the International Society of Craniofacial Surgeons, in Visby, Sweden, June 17 through 20, 2001; the 70th Annual Meeting of the American Society of Plastic Surgeons, in Orlando, Florida, November 3 through 7, 2001; and the 46th Annual Meeting of the Plastic Surgery Research Council, in Milwaukee, Wisconsin, June 9 through 12, 2001.

Disclosure: The authors have no financial interests or conflicts to disclose.

Jeffrey Weinzweig, M.D.; Craniofacial Biology and Tissue Engineering Laboratory; Department of Plastic Surgery; Lahey Clinic Medical Center; 41 Mall Road; Burlington, Mass. 01805; jeffrey.weinzweig@lahey.org

©2008American Society of Plastic Surgeons