Alterations in DNA Methylation in Orofacial Clefts

Orofacial clefts are among the most common craniofacial anomalies with multifactorial etiologies, including genetics and environments. DNA methylation, one of the most acknowledged mechanisms of epigenetics, is involved in the development of orofacial clefts. DNA methylation has been examined in patients with non-syndromic cleft lip with cleft palate (nsCL/P) from multiple specimens, including blood, saliva, lip, and palate, as well as experimental studies in mice. The results can be reported in two different trends: hypomethylation and hypermethylation. Both hypomethylation and hypermethylation can potentially increase the risk of nsCL/P depending on the types of specimens and the specific regions on each gene and chromosome. This is the most up-to-date review, intending to summarize evidence of the alterations of DNA methylation in association with the occurrence of orofacial clefts. To make things straightforward to understand, we have systematically categorized the data into four main groups: human blood, human tissues, animal models, and the factors associated with DNA methylation. With this review, we are moving closer to the core of DNA methylation associated with nsCL/P development; we hope this is the initial step to find a genetic tool for early detection and prevention of the occurrence of nsCL/P.