The effect of early childhood non-nutritive sucking behavior including pacifiers on malocclusion: a randomized controlled trial.

BACKGROUND/RATIONALE: Systematic reviews on the effects of pacifiers on occlusion have highlighted the need for quality RCTs. TRIAL DESIGN: Single region, three parallel-armed, prospective, randomized controlled trial. OBJECTIVES: To investigate the correlations between early childhood non-nutritive sucking habits and malocclusion. Specifically to test whether the use of a study pacifier has differing effects compared to other pacifiers and control, and whether the duration of pacifier use or digit sucking influence the occlusion. PARTICIPANTS: The subjects were firstborn children, born in 2008 in Vantaa, Finland. INTERVENTION: One-third of participants were offered study pacifiers, free of charge, from birth up to 2 years of age. The history of the subjects' sucking habits, including pacifier use was screened in a questionnaire at the age of 2 years, and clinical examinations were performed at the age of 7 years. In addition, the subjects were divided into groups that were equally matched regarding their mother's level of education. OUTCOMES: Posterior crossbite, anterior crossbite, overjet, deep bite, open bite, and crowding. RANDOMIZATION METHOD: Three districts were randomly allocated to three study groups by drawing lots. BLINDING: It was not possible to blind the clinicians or parents from the intervention. Blinding during data analysis was performed. RESULTS: From the original cohort of 2715 children born in the town of Vantaa, 1911 were excluded and 353 were lost to follow-up. The remaining 451 children were divided into three groups according to the use of pacifiers. The prevalence of posterior crossbite at the age of 7 years was higher if a non-study pacifier had been used (P = .005) even when matched for the mother's level of education (P = .029). The prevalence of posterior crossbite was higher if the pacifier habit had continued for 12 months or more compared to 11 months or less, 7% and 1%, respectively, (P = .003). Digit sucking for 12 months or more was associated with crowding (P = .016). The prevalence of crossbite in the study pacifier group was less than in control pacifiers. HARMS: No adverse harms were reported other than effects on the dentition. CONCLUSION: The use of pacifiers is associated with the posterior crossbite, especially if their use continues for a year or more. Parents/guardians should be advised to stop the use or reduce the use of pacifiers to a minimum after their child's first birthday. TRIAL REGISTRATION: ClinicalTrials.gov NCT01854502.

High incidence and geographic distribution of cleft palate cases in Finland are associated with a regulatory variant in IRF6.

In Finland the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We performed a genome-wide association study for orofacial clefts, which include CL/P and CP, in the Finnish population. We identified rs570516915, a single nucleotide polymorphism that is highly enriched in Finns and Estonians, as being strongly associated with CP ( P = 5.25 × 10 -34 , OR = 8.65, 95% CI 6.11-12.25), but not with CL/P ( P = 7.2 × 10 -5 ), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland ( P = 8.82 × 10 -28 ) and Estonia ( P = 1.25 × 10 -5 ). The risk allele of rs570516915 disrupts a conserved binding site for the transcription factor IRF6 within a previously characterized enhancer upstream of the IRF6 gene. Through reporter assay experiments we found that the risk allele of rs570516915 diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6 , suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

Is the third molar the most frequently extracted tooth? A population-based study utilizing dental panoramic radiographs in adults.

OBJECTIVES: The study aimed to examine the authenticity of the often-mentioned statement that the third molar is the most frequently extracted tooth. This finding has not been shown previously in a large population-based sample. MATERIALS AND METHODS: Data comprised a nationally representative sample of 6082 panoramic radiographs taken from adults in the cross-sectional Health 2000 Survey. From the radiographs, all missing teeth were recorded. Information on congenital agenesis of individual teeth was retrieved from two published meta-analyses. Primary outcome was the frequency of missing teeth by tooth type. Explanatory variables were age, sex, and the jaw (maxilla/mandible). Statistical analyses included χ2 test and binomial logistic regression. RESULTS: Mean age of participants (46% men, 54% women) was 53 years (SD 14.6; range 30‒97 years). Missing teeth occurred more often in women than in men (P < 0.001). The third molar was most frequently missing and the canine least frequently. In the maxilla and mandible, the third molar was missing more often than each of the other tooth types up to the age of 80 years (P < 0.01). CONCLUSIONS: When considering the rates of congenital agenesis of individual teeth, it is concluded that the third molar remained the most common tooth extracted up till the age of 80 years. CLINICAL RELEVANCE: The third molar is the most common target for extraction, but also the most common tooth associated with malpractice claims, and therefore, calls for skills, adequate equipment, and other resources for a successful extraction.

Longitudinal trends in temporomandibular joint disorder symptoms, the impact of malocclusion and orthodontic treatment: A 20-year prospective study.

BACKGROUND: Studies on the association between malocclusion and temporomandibular joint disorder (TMD) have reported conflicting results. OBJECTIVES: To determine the impact of malocclusion and orthodontic treatment on symptoms of TMD. METHODS: At 12 years, 195 subjects fulfilled a questionnaire regarding TMD symptoms and participated in an oral examination including preparation of dental casts. The study was repeated at ages 15 and 32. The occlusions were assessed by applying the Peer Assessment Rating (PAR) Index. Associations between the changes in PAR scores and TMD symptoms were analysed with the chi-square test. A multivariable logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of TMD symptoms at 32 years predicted by sex, occlusal traits and orthodontic treatment history. RESULTS: One in three subjects (29%) was orthodontically treated. Sex was associated with more self-reported headaches by females at 32 years (OR 2.4, 95% CI 1.05-5.4; p = .038). At all time points, any crossbite was significantly associated with greater odds for self-reported temporomandibular joint (TMJ) sounds at 32 years (OR 3.5, 95% CI 1.1-11.6; p = .037). More specifically, association occurred with posterior crossbite (OR 3.3, 95% CI 1.1-9.9; p = .030). At 12 and 15 years, boys whose PAR score increased were more likely to develop TMD symptoms (p = .039). Orthodontic treatment had no impact on the number of symptoms. CONCLUSIONS: Presence of crossbite may increase the risk of self-reported TMJ sounds. Also, longitudinal changes in occlusion may have an association with TMD symptoms while orthodontic treatment is not associated with the number of symptoms.

RAB23 regulates musculoskeletal development and patterning.

RAB23 is a small GTPase which functions at the plasma membrane to regulate growth factor signaling. Mutations in RAB23 cause Carpenter syndrome, a condition that affects normal organogenesis and patterning. In this study, we investigate the role of RAB23 in musculoskeletal development and show that it is required for patella bone formation and for the maintenance of tendon progenitors. The patella is the largest sesamoid bone in mammals and plays a critical role during movement by providing structural and mechanical support to the knee. Rab23 -/- mice fail to form a patella and normal knee joint. The patella is formed from Sox9 and scleraxis (Scx) double-positive chondroprogenitor cells. We show that RAB23 is required for the specification of SOX9 and scleraxis double-positive patella chondroprogenitors during the formation of patella anlagen and the subsequent establishment of patellofemoral joint. We find that scleraxis and SOX9 expression are disrupted in Rab23 -/- mice, and as a result, development of the quadriceps tendons, cruciate ligaments, patella tendons, and entheses is either abnormal or lost. TGFß-BMP signaling is known to regulate patella initiation and patella progenitor differentiation and growth. We find that the expression of TGFßR2, BMPR1, BMP4, and pSmad are barely detectable in the future patella site and in the rudimentary tendons and ligaments around the patellofemoral joint in Rab23 -/- mice. Also, we show that GLI1, SOX9, and scleraxis, which regulate entheses establishment and maturation, are weakly expressed in Rab23 -/- mice. Further analysis of the skeletal phenotype of Rab23 -/- mice showed a close resemblance to that of Tgfß2 -/- mice, highlighting a possible role for RAB23 in regulating TGFß superfamily signaling.

Craniofacial and dental features of Axenfeld-Rieger syndrome patients with PITX2 mutations.

We aimed to characterize the genetic basis and craniofacial and dental features of Finnish patients with Axenfeld-Rieger syndrome (ARS). Mutational analyses of seven patients in five families were performed by sequencing or comparative genomic hybridization. Phenotypic analysis was based on both clinical and radiographic examinations, as well as on medical data. Lateral cephalometric radiographs of five patients were analysed using Viewbox 3.1-Cephalometric Software. The cephalometric values were compared to Finnish population-standard values of the same age and gender. Two frameshift mutations and three whole gene deletions were detected in five families. Class III skeletal relationship with retrognathic maxilla and mildly retrognathic mandible were detected in all five patients studied. Significant differences compared with the control values were in SNA (P = .0014), ANB (P = .0043) and SNB angles (P = .013). Five patients had anterior crossbite. Six patients showed tooth agenesis. The average number of missing teeth (third molars excluded) was 9 (range 0-15). The tooth agenesis rate was 52% in maxilla and 26% in mandible. Maxillary central and lateral permanent incisors were most often missing (rate 71% equally) while no one lacked canines or first molars in mandible. Two patients had a supernumerary mandibular permanent incisor. Six patients had either taurodontic and/or single-rooted molars. Our results suggest that class III skeletal relationship with maxillary and mandibular retrognathism, anterior crossbite, maxillary incisor agenesis and taurodontic, even pyramidal, roots are common determinants of ARS caused by PITX2 mutations.

Dental age, agenesis, and morphological anomalies in individuals with Van der Woude syndrome and isolated cleft palate.

OBJECTIVES: To analyse the differences between dental age and chronological age and dental anomalies in individuals with Van der Woude syndrome (VWS) and compare with non-syndromic cleft palate (NSCP) and non-cleft controls. MATERIALS AND METHODS: In total, 204 oral panoramic radiographs (118 girls and 86 boys) consisting of 51 VWS patients (age x̅ = 8.17 ± 1.34 years), 51 NSCP patients (age x̅ = 8.09 ± 1.41 years), and 102 normative non-cleft children (age x̅ = 8.62 ± 1.24 years) were collected. Dental stages were assessed by the Demirjian method, with the local dental maturity index as reference. Dental anomalies including agenesis were investigated. Statistical differences were determined by One-way ANOVA and regression. Repeatability was calculated by an intra-class correlation test and 95% confidence interval. RESULTS: The difference between dental age and chronological age of the VWS group (0.12 years) and the NSCP group (0.09 years) was significantly lower than the non-cleft group (0.40 years) (P = 0.002). There was no significant difference between the VWS and NSCP groups (P = 0.885). Hypodontia was more prevalent in both the VWS group (37.25%, P = 0.0001) and the NSCP group (19.60%, P = 0.035) compared with the non-cleft group (5.88%). The odds for hypodontia in the VWS group were approximately double compared with the NSCP group. In VWS patients, the most commonly missing teeth were the permanent second premolars and the maxillary permanent laterals incisors. Peg-shaped teeth had a prevalence of 13.70% in VWS patients. CONCLUSIONS: In VWS and NSCP patients compared with non-cleft children, the difference in dental age compared with chronological age decreased. Hypodontia occurs at a high prevalence in VWS and NSCP patients compared with non-cleft children.

Taurodontism in the first permanent molars in Van der Woude syndrome compared to isolated cleft palate.

OBJECTIVES: To analyse prevalence, pattern, and severity of taurodontism in individuals with Van der Woude syndrome (VWS) exhibiting cleft palate and compare with aged-matched non-syndromic cleft palate (NSCP) and non-cleft controls. MATERIALS AND METHODS: One hundred and seventy-eight dental panoramic tomographs (DPTs) (105 girls and 73 boys) consisting of 42 VWS patients (x¯=8.55±1.02 years), 42 NSCP patients (x¯=8.59±1.02 years), and 94 normative non-cleft children (x¯=8.79±1.16 years) were assessed and their first permanent molars evaluated. Measurement 3 of the taurodontism index developed by Shifman and Chanannel with the Tulensalo modification was used. Prevalence, pattern, and severity were compared between groups. Statistical differences were determined by one-way analysis of variance and Fisher test. Repeatability was calculated by Cohens Kappa test. RESULTS: The prevalence of taurodontic molars was 59.5% in VWS, 45.2% in NSCP, and 26.6% in non-cleft controls. The prevalence and severity of taurodontism in VWS and NSCP were significantly higher than in non-cleft children in all first permanent molars. There was no significant difference in prevalence and severity between VWS and NSCP. The odds for having taurodontism in the VWS group was approximately double compared to the NSCP group. Most of the taurodontic molars showed hypotaurodontism and taurodontism occurred bilaterally more frequently than unilaterally. CONCLUSION: This study shows a higher prevalence of taurodontism in VWS and NSCP. Most taurodontic molars are hypotaurodontic and most occur bilaterally.

Dental Epithelial Stem Cells Express the Developmental Regulator Meis1.

MEIS1 is a key developmental regulator of several organs and participates in stem cell maintenance in different niches. However, despite the murine continuously growing incisor being a well described model for the study of adult stem cells, Meis1 has not been investigated in a dental context. Here, we uncover that Meis1 expression in the tooth is confined to the epithelial compartment. Its expression arises during morphogenesis and becomes restricted to the mouse incisor epithelial stem cell niche, the labial cervical loop. Meis1 is specifically expressed by Sox2+ stem cells, which give rise to all dental epithelial cell lineages. Also, we have found that Meis1 in the incisor is coexpressed with potential binding partner Pbx1 during both embryonic and adult stages. Interestingly, Meis2 is present in different areas of the forming tooth and it is not expressed by dental epithelial stem cells, suggesting different roles for these two largely homologous genes. Additionally, we have established the expression patterns of Meis1 and Meis2 during tongue, hair, salivary gland and palate formation. Finally, analysis of Meis1-null allele mice indicated that, similarly, to SOX2, MEIS1 is not essential for tooth initiation, but might have a role during adult incisor renewal.

Outcome quality and long-term (≥15 years) stability after Class II:2 Herbst-multibracket appliance treatment in comparison to untreated Class I controls.

Aim: To investigate the outcome quality and the long-term (≥15 years) post-treatment (Tx) changes after Class II:2 Herbst-multibracket appliance (MBA) Tx. Subjects and Methods: In this longitudinal observational study, a recall of Class II:2 patients who had been treated by a Herbst-MBA during adolescence was conducted. Study models from before and after active Tx, after retention and after recall were assessed using standard occlusal variables and the peer assessment rating index (PAR). These data were compared to historical untreated Class I controls. Results: Twenty out of 33 patients (61%) could be located and participated at age 33.9 ± 2.7 years. When comparing their data to the 13 patients who did not participate, the pre- and post-Tx occlusal findings did not differ systematically; however, the PAR scores of the non-participants were by 3.3-8.2 points higher at all times and the non-participants were 2.1-2.5 years older. Pre-Tx at age 14.4 ± 2.7 years, the participants showed the following mean values: PAR = 15.0 ± 7.0, Class II molar relationship (MR) = 0.8 ± 0.3 cusp widths (cw), overbite = 5.3 ± 1.3 mm. After Tx, a PAR score of 2.9 ± 1.3 and a super Class I MR (-0.1 ± 0.1 cw) with normal overbite (1.2 ± 0.8 mm) existed. At recall, a PAR score increase to 5.9 ± 3.6 points had occurred, mainly caused by an increase of overbite to 2.5 ± 1.5 mm. The average MR remained Class I (0.0 ± 0.2 cw). For all variables, the untreated controls exhibited similar findings. Conclusion: The occlusal outcome of Class II:2 Herbst-MBA Tx exhibited very good long-term stability. While mild post-Tx changes occurred, the long-term findings are similar to untreated Class I controls.