School of Medicine and School of Dentistry, University of Utah Health, Salt Lake City, UT, USA.
Department of Biomedical Engineering, College of Engineering, University of Utah, Salt Lake City, UT, USA.
J Dent Res. 2020 Oct;99(11):1221-1227. doi: 10.1177/0022034520936245. Epub 2020 Jul 1.
Orofacial clefts and their management impose a substantial burden on patients, on their families, and on the health system. Under the current standard of care, affected patients are subjected to a lifelong journey of corrective surgeries and multidisciplinary management to replace bone and soft tissues, as well as restore esthetics and physiologic functions while restoring self-esteem and psychological health. Hence, a better understanding of the dynamic interplay of molecular signaling pathways at critical phases of palate development is necessary to pioneer novel prenatal interventions. Such pathways include transforming growth factor-β (β), sonic hedgehog (), wingless-integrated site ()/β-catenin, bone morphogenetic protein (), and fibroblast growth factor () and its associated receptors, among others. Here, we summarize commonly used surgical methods used to correct cleft defects postnatally. We also review the advances made in prenatal diagnostics of clefts through imaging and genomics and the various in utero surgical corrections that have been attempted thus far. An overview of how key mediators of signaling that drive palatogenesis are emphasized in the context of the framework and rationale for the development and testing of therapeutics in animal model systems and in humans is provided. The pros and cons of in utero therapies that can potentially restore molecular homeostasis needed for the proper growth and fusion of palatal shelves are presented. The theme advanced throughout this review is the need to develop preclinical molecular therapies that could ultimately be translated into human trials that can correct orofacial clefts at earlier stages of development.
口面裂及其治疗给患者、患者家庭和医疗系统带来了沉重负担。在现行治疗标准下，患者需要经历终生的矫正手术和多学科管理，以重建骨骼和软组织，恢复美观和生理功能，同时恢复自尊心和心理健康。因此，有必要深入了解腭发育关键阶段中分子信号通路的动态相互作用，以开创新型产前干预措施。这些途径包括转化生长因子-β（β）、 sonic hedgehog ()、wingless-integrated site ()/β-catenin、骨形态发生蛋白（）和 fibroblast growth factor () 及其相关受体等。在这里，我们总结了常用的腭裂修复术。我们还回顾了通过影像学和基因组学在产前诊断唇腭裂方面取得的进展，以及迄今为止尝试过的各种宫内手术矫正方法。本文概述了信号转导的关键介质如何在动物模型系统和人类中促进治疗药物的开发和测试的框架和原理背景下发挥作用，强调了腭形成的信号转导。本文还介绍了潜在的宫内治疗方法的优缺点，这些方法可以恢复腭板正常生长和融合所需的分子内稳态。本综述贯穿的主题是需要开发临床前分子治疗方法，最终可以转化为纠正口面裂的人类临床试验。
