Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors.

Marcella Martinelli,Luca Scapoli,Francesco Carinci,Annalisa Palmieri

doi:10.3389/fcell.2020.592271

Abstract

The epithelial and mesenchymal cells involved in early embryonic facial development are guided by complex regulatory mechanisms. Any factor perturbing the growth, approach and fusion of the frontonasal and maxillary processes could result in orofacial clefts that represent the most common craniofacial malformations in humans. The rarest and, probably for this reason, the least studied form of cleft involves only the secondary palate, which is posterior to the incisive foramen. The etiology of cleft palate only is multifactorial and involves both genetic and environmental risk factors. The intention of this review is to give the reader an overview of the efforts made by researchers to shed light on the underlying causes of this birth defect. Most of the scientific papers suggesting potential environmental and genetic causes of non-syndromic cleft palate are summarized in this review, including genome-wide association and gene–environment interaction studies.

Highlights

Orofacial clefts are the most common orofacial malformations in humans and include cleft lip (CL), cleft lip with or without cleft palate (CL/P), and cleft palate only (CPO)
Several evidences have highlighted the fact that non-syndromic CPO (NSCPO) and NSCL/P are different malformations with different, or slightly overlapping, causes
Scientific research has been mainly focused on NSCL/P, while NSCPO study has been marginal, maybe owing to the lower incidence that makes harder to collect cohorts of comparable size

Summary

Introduction

Orofacial clefts are the most common orofacial malformations in humans and include cleft lip (CL), cleft lip with or without cleft palate (CL/P), and cleft palate only (CPO). These authors highlighted the teratogenic effect of hyperthermia, which was confirmed the following year by Acs et al (2006), who reported that the fever associated with acute respiratory infections seemed to increase the risk for posterior cleft palate in their Hungarian sample study.

Results

Conclusion