The precise role that genes play in early craniofacial development and postnatal craniofacial growth are essential to understand dento-facial development overall. However, genotype-phenotype correlations between genetic variation of early craniofacial genes and adult craniofacial phenotypes is poorly understood. Thus, this thesis focused on identifying the genetic etiology underlying phenotypic variations present in malocclusion conditions. First, we performed genotype-phenotype association analyses between common variants in 82 craniofacial genes and phenotypic variations extracted from 2D and 3D pre-treatment dental records of individuals with malocclusion. This effort identified that variant rs2189000 upstream of TWIST1 is highly associated with mandibular body length and inclination and cranial base angulations which can lead to malocclusion. Next, via cell based functional assays, we discovered that rs2189000 disrupts a PITX2 binding site and also showed the direct regulation of TWIST1 expression by the PITX2 gene. Finally, we identified abnormal craniofacial phenotypes and malocclusion in Twist1 deleted mice including asymmetric snouts, domed cranial vaults, and changes in size and inclination of the cranial base, palate and mandible resulting in malocclusion and resembling the human phenotypes observed. Also, premature calcification of calvarial sutures and cranial base synchondroses were also observed in the mutant mice indicating a possible biological mechanism for the abnormal phenotypes detected. These results confirm that TWIST1 is an important regulator of postnatal growth and that genetic variation in TWIST1 can result in malocclusion. The continued identification of genetic etiological factors and their role in craniofacial growth will impact treatment and prevention of malocclusion and other craniofacial conditions

Introduction: This study aimed to evaluate and quantify extraction spaces and their behavior at the end of treatment, short- and long-term stages, in orthodontic patients treated with extractions. Methods: The sample comprised dental casts of 1546 orthodontic patients treated with extractions with several malocclusions. Dental casts were divided into 3 groups, according to the chronological stage: at the end of treatment (T0), 1-year posttreatment (short-term, T1) and 5-year posttreatment (longterm, T2). Extraction spaces were measured in the three stages with a digital caliper. The descriptive analyses of the longitudinal space behavior were performed by amounts of patients, percentage of patients and percentage of quadrants. Intergroups comparison of space dimension in the three stages were performed by Analysis of Variance, followed by Tukey tests when necessary. Results: Class II malocclusion was the most prevalent sagittal discrepancy, followed by Class I and Class III, respectively. More than a half of the patients presented 1-4 quadrants open at the end of treatment. Less than 10% of quadrants persisted open at the three stages. Most of relapse and late closure occurred in the first year after treatment. About 5% of quadrants closed at T0 presented relapse at T1. Less than 3% of quadrants closed at T1 presented relapse at T2. Space dimension decreased significantly in the long-term evaluation. Conclusions: The percentage of patients with open spaces at the end of treatment was substantially large. Despite of the late space closure tendency, several spaces may remain open in the long-term. There was significant reduction in extraction space dimension in the long-term. / Introdução: O objetivo deste estudo foi avaliar e quantificar os espaços das extrações e seu comportamento ao final do tratamento, em curto e longo prazos. Materiais e métodos: a amostra consistiu em modelos ortodônticos de 1546 pacientes tratados ortodonticamente com extrações com diversas más oclusões. Os modelos foram divididos em 3 grupos, de acordo com o estágio cronológico: ao final do tratamento (T0), 1 ano pós-tratamento (curto prazo, T1) e 5 anos pós-tratamento (longo prazo, T2). Os espaços das extrações foram mensurados nos três estágios com um paquímetro digital. As análises descritivas do comportamento longitudinal foram realizadas por quantidade de pacientes, porcentagem de pacientes e porcentagem de quadrantes. A comparação intergrupos da dimensão do espaço nos três estágios foi realizada através da Análise de Variância, seguida pelo Teste Tukey quando necessário. Resultados: A má oclusão de Classe II foi a discrepância sagital mais prevalente, seguida pela Classe I e Classe II, respectivamente. Mais da metade dos pacientes apresentaram 1-4 quadrantes abertos ao final do tratamento. Menos de 10% dos quadrantes persistiram abertos nos três estágios. A maioria das reaberturas e fechamentos tardios ocorreu no primeiro ano pós-tratamento. Aproximadamente 5% dos quadrantes fechados em T0 apresentaram reabertura em T1. Menos de 3% dos quadrantes fechados em T1 apresentaram reabertura em T2. A dimensão do espaço diminuiu significativamente na avaliação em longo prazo. Conclusão: A porcentagem de pacientes com espaços abertos ao final do tratamento foi substancialmente grande. Apesar da tendência de fechamento tardio, muitos espaços podem restar abertos em longo prazo. Houve redução significante na dimensão dos espaços das extrações em longo prazo.

Introduction: This study aimed to assess the third molars angulation and their available space after Class II subdivision malocclusion treatment with asymmetric premolar extractions. Methods: The sample consisted of 37 patients in group 1 (Type 1 Class II subdivision) and 25 in group 2 (Type 2 Class II subdivision). In group 1 extractions were performed in the two maxillary quadrants and in the Class I mandibular quadrant. In group 2, extraction was performed in the Class II maxillary quadrant. Panoramic radiographs were used to evaluate third molars angulation and their available space. Radiographic measurements were performed with Dolphin® Imaging 11.9. T tests were used for intragroup comparison between the sides. Results: Generally, the results showed that both Groups demonstrated more favorable angulation and significantly greater space for third molars on the extraction quadrants. Both groups presented mesioangulation in mandibular third molars on the Class II side. Conclusions: Extraction therapy is associated with an improvement of space available and third molars angulation on the extraction quadrants. / Introdução: O objetivo desse estudo é avaliar a angulação e o espaço disponível para irrupção dos terceiros molares após o tratamento da Classe II subdivisão com extrações assimétricas de pré-molares. Materiais e métodos: A amostra foi constituída por 37 pacientes no grupo 1 (Classe II subdivisão tipo 1) e 25 no grupo 2 (Classe II subdivisão tipo 2). No grupo 1 as extrações foram realizadas nos 2 quadrantes superiores e 1 no inferior do lado da Classe I. Na tipo 2, foi realizada 1 extração no arco superior do lado da Classe II. Radiografias panorâmicas foram utilizadas para avaliar as angulações e os espaços dos terceiros molares. As medições radiográficas foram realizadas no programa Dolphin® Imaging 11.9. Testes t foram utilizados nas comparações intragrupos entre tempos e os lados. Resultados: No geral, os resultados mostraram que os dois Grupos demonstraram angulações mais favoráveis e aumentos significantemente maiores para os terceiros molares dos quadrantes das extrações. Conclusão: Tratamento com extração está associado com aumento do espaço disponível e melhora na angulação dos terceiros molares nos quadrantes das extrações.

Objetivo: El objetivo de este estudio fue evaluar la correlación entre el patrón esquelético y el patrón facial en radiografías cefalométricas en pacientes con deformidad dentofacial clase I y III. Materiales y métodos: El presente estudio fue de tipo transversal. La muestra estuvo constituida por 160 radiografías cefalométricas digitales (40 por cada género y clase). El análisis se realizó con la ubicación de los puntos cefalométricos con el programa VixWinPlatinium® según el análisis de Steiner para tejidos duros y Burstone - Legan para tejidos blandos. El análisis de datos se realizó mediante estadística descriptiva (media ±de) y la correlación de ambos análisis mediante Correlación de Pearson. Resultados: Los resultados indicaron que no existe correlación entre el patrón esquelético y facial en pacientes con deformidad dentofacial clase I. En hombres 0.15 (p= 0,353) y mujeres -0.12 (p= 0,433). Por otro lado, en pacientes con deformidad dentofacial clase III, sí se obtuvo correlación con 0.41 en mujeres (p= 0,08) y en hombres 0.32 (p=0,008). Conclusiones: Basado en los datos mencionados se puede determinar que el sexo no es un factor determinante para hallar el diagnóstico y tratamiento de pacientes con deformidades dentofaciales clase I y III. / Objective: The objective of this study was to evaluate the correlation between the skeletal pattern and the facial pattern in cephalometric radiographs in patients with dentofacial deformities class I and III. Materials and methods: The following was a cross-sectional or transverse study. The sample consisted of 160 digital cephalometric radiographs (40 for each gender and class). The analysis was performed by identifying locations of cephalometric points using the VixWinPlatinium ® program, then hard tissues were further evaluated according to the Steiner analysis and Burstone-Legan for soft tissues. The data analysis was performed by means of descriptive statistics (mean ± of) and the correlation of both analysis by means of Pearson correlation. Results: The results indicated that there is no correlation between the skeletal and facial pattern in patients with dentofacial deformity class I. In men 0.15 (p = 0.353) and women -0.12 (p = 0.433). On the other hand, in patients with dentofacial deformity class III, correlation was obtained with 0.41 in women (p = 0.08) and in men 0.32 (p = 0.008). Conclusions: Based on the aforementioned data, it can be determined that sex is not a determining factor to find the diagnosis and treatment of patients with dentofacial deformities class I and III. / Tesis

During the last three decades there has been an increased influx of refugees and immigrants into Scandinavia. The overall aim of this thesis was primarily to improve our knowledge of malocclusion and orthodontic treatment need, both normative and self-perceived, in adolescents of varying geographic origin. A further aim was to determine whether any differences with respect to perception of general appearance and psychosocial well-being were related to geographic origin. Papers I and II concerned self perceived and normative orthodontic treatment need. About 500 12-13 year-old subjects, stratified into different groups: A-Sweden, B-Eastern/Southeastern Europe, C-Asia and D-other countries, answered a questionnaire and underwent clinical examination by the author. In paper III the association between the two variables in papers I and II was investigated. Paper IV was a follow up study, at 18-19 years of age, of the relationship between geographic origin and prevalence of malocclusion, self-perceived treatment need, temporomandibular symptoms and psychosocial wellbeing. In Paper V a qualitative study of 19-20 year old subjects was conducted, to identify the strategies they had adopted to handle the issue of persisting poor dental aesthetics. The main findings were that at 12-13 years of age, immigrant subjects had a lower perceived orthodontic treatment need than subjects of Swedish background. Girls of Swedish background had the highest self perceived treatment need, whilst girls of non-Swedish background were most concerned that fixed appliance therapy would be painful. In a few of the clinical variables measured at 12-13 years of age, the Swedish group exhibited the greatest space deficiency and irregularity in both the maxillary and mandibular anterior segments and greater overjet, compared to the Eastern/Southeastern European and Asian groups. The clinical implications were negligible. The orthodontic treatment need according to “Index of Orthodontic Treatment Need - Dental HealthComponent” (IOTN-DHC) grades 4 and 5, ranged from 30 to 40 percent, without any inter-group differences. There were strong associations between subjects perceiving a need for orthodontic treatment and 6IOTN-DHC grades 4 and 5, anterior crossbite and avoiding smiling because they were self-conscious about their teeth. At the age of 18-19 years, the frequency of malocclusion was similar in all groups. Subjects of Asian origin had a higher self-perceived orthodontic treatment need than their Swedish counterparts and a higher frequency of headache than those of Eastern/Southeastern European origin. Psychological wellbeing was reduced in nearly one quarter of the sample, more frequently in girls than boys. No association was found between self-perceived orthodontic treatment need and psychological wellbeing. The theory “Being under the pressure of social norms” was generated in Paper V, and it can be applied to improve our understanding of young adults who have adjusted to living with poor dental aesthetics and also aid to identify those who are not as well-adjusted and would probably benefit from treatment. Undisclosed dental fear is an important barrier to acceptance of orthodontic treatment in early adolescence. Despite demographic changes due to immigration, no major change in the prevalence of malocclusion and normative orthodontic treatment need has been disclosed. This does not apply to adolescents and adults who immigrated at an older age.

Thesis (M.S.)--University of Michigan, 1969.

Doktoravhandling--Copenhagen. / Bibliography: p. 97-[100].

Thesis (M.S.)--University of Michigan, 1969.

Doktoravhandling--Copenhagen. / Bibliography: p. 97-[100].

Diss. med. dent. Zürich. / Literaturverz.