Identification of dental calcification stages as a predictor of skeletal development phase.

OBJECTIVE: This study aimed to establish a correlation between the stages of tooth calcification of mandibular canines and second molars with the phases of skeletal development. METHODS: In a consecutive series of panoramic, cephalometric and hand-wrist radiographs of 113 individuals (60 females and 53 males) with an average age of 12.24 ± 1.81 years, the stages of mandibular canine and second molar calcification, cervical vertebrae maturation indicators (CVMI) and skeletal maturity indicators (SMI) were classified. The variables were correlated by means of the Spearman's Rank test: chronological age, SMI, CVMI and tooth calcification stages. In order to assess whether the CVMI and tooth calcification stages were significant predictors of the SMI, an ordinal regression analysis was carried out. RESULTS: The stages of CVMI (OR = 16.92; CI 95% = 6.45-44.39; p< 0.001) and calcification of the second molars (OR = 3.22; CI 95% = 1.50-6.92; p= 0.003) were significant predictors of SMI, however similar result was not observed for canines (OR = 0.52, CI 95% = 0.18-1.54; p= 0.239). Calcification stage E for boys, and E and F for girls corresponded to the pre-peak phase of pubertal growth. Stages G and H for boys, and F and G for girls coincided with peak of growth. In the final growth phase, the majority of second molars presented with root apex closure (stage H). CONCLUSION: The stages of calcification of the second molar may be considered predictors of the stage of skeletal development in the population studied.

Retrognathic maxilla in individuals born with oral clefts is due to intrinsic factors and not only due to early surgical treatment.

OBJECTIVES: To determine if the skeletal form of individuals born with oral clefts was associated with maxillary position. MATERIALS AND METHODS: Lateral cephalometric radiographs of 90 individuals 8 to 12 years old born with or without cleft lip and palate paired by age and sex were used. Skull base length, cranial base angle, cranial deflection angle, and maxillary skeletal length and position were studied. Also, mandibular skeletal length and position, lower anterior facial height, and dental position were defined. Individuals were divided into three groups: 30 individuals born with cleft lip and palate with Class III malocclusion (UCLP Class III), 30 individuals born with cleft lip and palate with Class I malocclusion (UCLP Class I), and 30 individuals born without cleft lip and palate with Class III malocclusion (non-cleft Class III). RESULTS: When comparing the UCLP Class III group with the UCLP Class I group, there were differences in maxillary position (P < .001) and mandibular position (P = .004) found. No differences were found when comparing the UCLP Class III group with the non-cleft Class III group. CONCLUSIONS: There are intrinsic factors that affect craniofacial morphology of individuals born with cleft lip and palate.

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

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.

IRE1 Less Common Homozygous Genotype in Families With Positive History of Cancer and Individuals Born With Cleft Lip/Palate.

ABSTRACT: The aim of this study was to test if the marker rs196929 in IRE1 associated with cleft lip and palate depending on the family history for cancer. A consecutive sample of 836 individuals were recruited between April and October of 2019 (303 born with cleft lip and palate, 256 relatives mostly of the maternal side of individuals born with cleft lip and palate, and 277 unaffected unrelated individuals). Parents or guardians of the children answered a questionnaire with basic demographic information about their children and their family history of cleft lip and palate and cancer. DNA was obtained from whole saliva and IRE1 rs196929 was genotyped using TaqMan chemistry and end-point analysis. Over-representation of alleles was determined using chi-square as implemented in PLINK using an alpha of 0.05. There was an excess of less common homozygotes of IRE1 rs196929 among relatives of individuals born with cleft lip and palate when they had positive family history of cancer in comparison with individuals born with cleft lip and palate or with unrelated unaffected individuals (P = 0.0006 and P < 0.001, respectively). This pattern was similar when families reported one type of cancer or multiple ones, or when cancer affecting females (breast or reproductive tract) or the structures of the gastro-intestinal tract were considered. These results provide support for a role of the ER stress IRE1-XPB1 pathway in the higher frequency of cancer in families of individuals born with cleft lip and palate.

Identification of dental calcification stages as a predictor of skeletal development phase

ABSTRACT Objective: This study aimed to establish a correlation between the stages of tooth calcification of mandibular canines and second molars with the phases of skeletal development. Methods: In a consecutive series of panoramic, cephalometric and hand-wrist radiographs of 113 individuals (60 females and 53 males) with an average age of 12.24 ± 1.81 years, the stages of mandibular canine and second molar calcification, cervical vertebrae maturation indicators (CVMI) and skeletal maturity indicators (SMI) were classified. The variables were correlated by means of the Spearman's Rank test: chronological age, SMI, CVMI and tooth calcification stages. In order to assess whether the CVMI and tooth calcification stages were significant predictors of the SMI, an ordinal regression analysis was carried out. Results: The stages of CVMI (OR = 16.92; CI 95% = 6.45-44.39; p< 0.001) and calcification of the second molars (OR = 3.22; CI 95% = 1.50-6.92; p= 0.003) were significant predictors of SMI, however similar result was not observed for canines (OR = 0.52, CI 95% = 0.18-1.54; p= 0.239). Calcification stage E for boys, and E and F for girls corresponded to the pre-peak phase of pubertal growth. Stages G and H for boys, and F and G for girls coincided with peak of growth. In the final growth phase, the majority of second molars presented with root apex closure (stage H). Conclusion: The stages of calcification of the second molar may be considered predictors of the stage of skeletal development in the population studied.

RESUMO Objetivo: O presente estudo objetivou estabelecer uma correlação entre os estágios de calcificação dentária de caninos e segundos molares inferiores e as fases do desenvolvimento esquelético. Métodos: Em uma série consecutiva de radiografias panorâmicas, cefalométricas e de mão e punho de 113 indivíduos (60 meninas e 53 meninos) com idade média de 12,24 ± 1,81 anos, foram classificados os estágios de calcificação do canino e do segundo molar inferiores, indicadores de maturação das vértebras cervicais (IMVC) e indicadores de maturação esquelética (IME). As variáveis foram correlacionadas pelo teste de Correlação de Rank de Spearman: idade cronológica, IME, IMVC e estágios de calcificação dentária. A fim de avaliar se os estágios do IMVC e da calcificação dentária foram preditores significativos do IME, foi realizada uma análise de regressão ordinal. Resultados: Os estágios de IMVC (OR = 16,92; IC 95% = 6,45-44,39; p< 0,001) e calcificação dos segundos molares (OR = 3,22; IC 95% = 1,50-6,92; p= 0,003) foram preditores significativos de IME; no entanto, esse não foi o caso com dentes caninos (OR = 0,52, IC 95% = 0,18-1,54; p= 0,239). Os estágios de calcificação E para meninos e E e F para meninas corresponderam à fase pré-pico de crescimento puberal. Os estágios G e H para meninos e F e G para meninas coincidiram com o pico de crescimento. Na fase final de crescimento, a maioria dos segundos molares apresentou fechamento do ápice radicular (estágio H). Conclusão: Os estágios de calcificação do segundo molar podem ser considerados preditores do estágio de desenvolvimento esquelético na população estudada.

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

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in the MMP2 genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker in MMP2 (rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student's t-test and the Mann-Whitney test. Chi-square and Fisher's exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p <0.001; OR = 7.15, CI: 4.674> 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p <0.001). Regardless of the cleft side, individuals with BCLP were 7.85 times more likely to have more than one third of the tooth surface affected, showing more frequently defects in the three thirds (OA: p <0.001) (IA: p = 0.03), as well as a higher frequency of more than one type of defect (OA: p = 0.000358) (IA: p = 0.008016), whereas in UCLP, defects were isolated and restricted to only one third, more frequently, the incisal third (OA: p = 0.009) (IA: p = 0.001), with greater frequency of milder defects, such as demarcated (p = 0.02) and diffuse (p = 0.008) opacities. A higher frequency of the T allele, less common, was observed in the group of CLP individuals who had all the affected teeth or at least two teeth with %SAD greater than 20% (p = 0.019843). Our results suggest that MMP2 may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP. Frequency and severity of DDE is strongly related to the CLP phenotype, since the highest values were found for BCLP. However, the extent of the DDE is independent of its relationship with the side of the cleft.