Talon Cusp Associates With MMP2 in a Cohort of Individuals Born With Oral Clefts

Abstract

Objective: The aim of this study was to use dental development as a tool to subphenotype oral clefts and investigate the association of MMP2 with dentin-pulp complex anomalies, in order to identify dental anomalies that are a part of a “cleft syndrome.” Design: Two hundred and ninety individuals born with cleft lip and palate were evaluated and several clinical features, such as cleft completeness or incompleteness, laterality, and presence of dental anomalies were used to assess each individual’s cleft status. We tested for overrepresentation of MMP2 single nucleotide polymorphism rs9923304 alleles depending on individuals having certain dental anomalies. Chi-square and Fisher exact tests were used in all comparisons (α = .05). Results: All individuals studied had at least one dental anomaly outside the cleft area. Significant differences between individuals born with clefts with and without talon cusp ( P = .04) were observed for the frequency of the MMP2 less common allele. Conclusion: All individuals born with cleft lip and palate had alterations of the dentition, and a quarter to half of the individuals had alterations of the internal anatomy of their teeth, which further indicates that dental anomalies can be considered as an extended phenotype for clefts. MMP2 was associated with talon cusp in individuals born with oral clefts.

Dental Anomalies and Genetic Polymorphisms as Predictors of Maxillofacial Growth in Individuals Born with Cleft Lip and Palate

“…The high frequency of dental anomalies found here, with at least 1 anomaly per individual, was previously reported (Letra et al 2007; Cavalcante et al 2021) and reinforces the thesis that dental anomalies can be considered an extension of the cleft phenotype (Koruyucu et al 2018; Cavalcante et al 2021).…”

“…MMP2 rs9923304 was also associated with enamel structural defects and morphological dental anomalies, which is also not surprising due to the role of MMP2 in tooth formation and mineralization (Bourd-Boittin et al 2005). We previously reported the association of MMP2 rs9923304 with talon cusp (Cavalcante et al 2021) and enamel defects in individuals born with cleft lip and palate (Lavôr et al 2020). These findings may suggest that maxillary growth, enamel defects, and dental shape anomalies in individuals born with cleft lip and palate are the result of alterations of the same genetic pathway.…”

“…Cleft lip and palate is the most common congenital anomaly in the human face and has multifactorial inheritance (Vieira 2008). Common genetic factors and neural crest cell origin may explain a high frequency of dental anomalies found in individuals born with cleft lip and palate (Letra et al 2007; Cavalcante et al 2021).…”

Maxillary incisor enamel defects in individuals born with cleft lip/palate

“…Previous studies have demonstrated that genes involved in enamel development are associated with DDE [21,48,49]. Also, studies have shown the association of MMP2 with formation and mineralization of dental tissues [23][24][25], and dental conditions such as periapical lesions [50], non-carious loss of extensive composite resin restorations [22], and talon cusp [51]. However, this was the first time this gene was specifically studied for DDE.…”

A Need for Updating the Research Agenda for Cleft Lip and Palate and Extending the Cleft Team Model to Dental Medicine

“…Cleft lip and palate appears to be accompanied with minor defects, in particular changes in dental development [reviewed in (9,10)]. Virtually, all individuals born with cleft lip and palate have dental development alterations outside the cleft area [i.e., the posterior maxillary teeth and/or mandibular teeth; (14)], and delayed dental development or tooth eruption, which implies a delay in start of orthodontic treatment (15), and it has been proposed that cleft lip and palate is always a syndrome of the dentition (16). The challenge of these assumptions, however, is that the historical cohorts recruited at birth do not have any descriptions of the dentition and recovering that information would not be a trivial task.…”