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

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.

The Challenge of 3D Bioprinting of Composite Natural Polymers PLA/Bioglass: Trends and Benefits in Cleft Palate Surgery

“…At the same time, between the sixth and ninth week, the lateral palatal processes fuse after the secondary palate has been brought closer to the primary palate with a junction marked by the incisal foramen [ 10 ]. Multiple genetic (e.g., mutation on IRF6, MAFB, ABCA4 genes) and environmental factors (e.g., maternal smoking, maternal alcohol, nutritional factors, radiations) influence the growth, approach, and fusion of the fronto-nasal and maxillary processes [ 19 ]. These factors can lead to local changes in growth factors, extracellular matrix (ECM) and cell adhesion molecules to the point of causing a lack of fusion processes, leading to secondary cleft palate [ 20 ].…”

Pregnant mother's knowledge level and its determinant factors towards preventable risk factors of congenital anomalies among mothers attended health institutions for antenatal care, Ethiopia

“…13 Another evidence suggested that the causes of some congenital anomalies can be related to multifactorial origins [14][15][16] and environmental factors. 17,18 Because of these, investigating the underlining causes and risk factors of congenital anomalies may help to decrease the incidence of birth defects which is related to preventable risk factors of congenital anomalies and at present, vaccination, dietary intake of folate or iodine, preconception health care and ultrasound evaluation during pregnancy are available options for prevention of some form of birth defect. [19][20][21] Similar to developing countries, the prevalence of congenital anomalies in Ethiopia is also raising.…”

Concepts in Multifactorial Etiology of Developmental Disorders: Gene-Gene and Gene-Environment Interactions in Holoprosencephaly

“…These factors interact with each other to affect the strength and duration of key developmental signaling pathways, thereby increasing the possibility that they fail to achieve the thresholds required for normal patterning. The same is likely true of many common birth defects, including congenital heart defects, neural tube defects, and oro-facial clefting (Krauss and Hong, 2016;Beames and Lipinski, 2020;Martinelli et al, 2020;Finnell et al, 2021;Kodo et al, 2021). Genome sequencing analyses and epidemiology, plus mechanistic studies with animal models, have provided conceptual insights into HPE etiology which should prove applicable to these other developmental disorders.…”