Exploring the Association Between Genetic Polymorphisms in Genes Involved in Craniofacial Development and Isolated Tooth Agenesis

Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated tooth agenesis and genetic polymorphisms in genes that are crucial for craniofacial and tooth development. Panoramic radiographs, anamnesis, and genomic DNA from 273 patients were included. Patients were classified as tooth agenesis present, when at least one permanent tooth was congenitally missing. Patients with syndromes and oral cleft were excluded. Only unrelated patients were included. The genetic polymorphisms in BMP2 (rs235768 and rs1005464), BMP4 (rs17563), RUNX2 (rs59983488 and rs1200425), and SMAD6 (rs3934908 and rs2119261) were genotyped by real-time polymerase chain reaction. Genotype and allele distributions were compared between the tooth agenesis phenotypes and controls by Chi-square test. Haplotype and diplotype analysis were also performed, in addition to multivariate analysis (alpha of 0.05). A total of 86 tooth agenesis cases and 187 controls were evaluated. For the rs235768 in BMP2, patients carrying TT genotype have higher chance to present tooth agenesis [p < 0.001; prevalence ratio (PR) = 8.29; 95% confidence interval (CI) = 4.26–16.10]. The TT genotype in rs3934908 (SMAD6) was associated with higher chance to present third molar agenesis (p = 0.023; PR = 3.25; 95% CI = 1.17–8.99). BMP2 was also associated in haplotype and diplotype analysis with tooth agenesis. In conclusion, genetic polymorphisms in BMP2 and SMAD6 were associated with isolated tooth agenesis.

Patterns of dental anomalies in patients with nonsyndromic oral cleft

Aim: To characterize the patterns of dental anomalies (DA) in the mixed and permanent dentitions of patients with nonsyndromic oral cleft (NSOC). Methods: This cross-sectional, observational, case-control study included 173 patients, 61 with mixed dentition (NSOC=29 and control=32) and 112 with permanent dentition (NSOC=57 and control=55). All subjected were submitted to clinical and radiographic examination. Dental anomalies of eruption, number, size and shape outside the cleft area were considered. Results: Although there was no statistical significance among patients with mixed dentition, dental agenesis was the anomaly more common in this group. In patients with permanent dentition, a higher prevalence of DA in NSOC group compared to control group was observed (p=0.02). Gyroversion and dental agenesis were the DA more frequently observed in the permanent dentition and the second premolar was the tooth more affected (p=0.003). Mandible and the left side were more involved, and dental agenesis was more frequently found in patients with unilateral cleft lip with or without cleft palate (NSCL±P). Conclusion: Our findings show a higher frequency of DA in NSOCs than in the control group in patients with permanent dentition, mainly due to a higher occurrence of agenesis of second premolars in patients with unilateral NSCL±P.

Effects of anesthesia and oral cleft types on academic achievement

ObjectiveResearch looking simultaneously at the effects of anesthesia and oral cleft types on academic achievement is scarce. Available results are contradictory: some studies suggest that anesthesia exposure is responsible for underachievement, and others that responsibility falls instead on the type of orofacial cleft. This study investigates the potential compound effects of exposure to anesthesia and orofacial cleft types on the risk of academic underachievement.DesignCentre Labio Palatin Albert Coninck, Cliniques universitaires Saint-Luc, Brussels, Belgium, nationwide register-based study.SettingBirth cohort 1995-2007.PatientsTwenty-nine children with isolated orofacial clefts exposed to anesthesia.InterventionsAverage duration of exposure to anesthesia before the Certificat d Etudes de Base (CEB) exam was 382 minutes.Main Outcome Measure(s)Scores obtained by patients at the CEB exam were compared with the scores of the 6th grade Belgian general population who passed the same exam controlling for gender, school year, year they passed the exam, medical illnesses, duration of exposure to anesthesia in minutes and socioeconomic confounders.ResultsDoubling the time of anesthesia exposure produces a 17 percentage point increase in the probability that patients will underachieve. Cleft lip reduces while cleft right-left increases the duration of anesthesia exposure relative to cleft lip palate. Results do not change when anesthesia exposure only up to 4 years and socioeconomic factors are considered.ConclusionsBoth exposure to anesthesia and different types of orofacial cleft may result in underachievement at the CEB exam.

Association between oral cleft and transcobalamin 2 polymorphism in a sample study from Nassiriya, Iraq

Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene ( P = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity.