Genes candidatos às anomalias dentárias em pacientes portadores de maloclusão esquelética / Candidate genes for dental anomalies in patients skeletal malocclusion

O objetivo do presente estudo foi verificar a presença de associação fenótipo-genotípico entre TGFA (Fator de Crescimento Transformante α) (C/T rs1523305), IRF6 (Fator Regulatório Interferon 6) (A/C rs2013162) e MSX1 (Segmento Muscular Homeobox 1) (A/G rs12532) e anomalias dentárias em pacientes com malclusão esquelética. Para tanto, dois estudos prévios foram realizados com os objetivos de (I) determinar se indivíduos com discrepâncias esqueléticas de Classe II ou III apresentam uma maior frequência de anomalias dentárias em comparação com indivíduos com maloclusão de Classe I e (II) comparar quatro diferentes métodos de coleta salivar e de células bucais [Expectoração da Saliva (1), Expectoração da Saliva com Estímulo Lingual (2), Raspagem com Escova Citológica (3) e Raspagem com Escova Citológica mais Expectoração da Saliva (4)] para extração de DNA genômico, avaliando sua concentração e pureza. Na revisão sistemática, foi realizada uma busca nas principais bases de dados da literatura científica médica eletrônica. Estudos observacionais foram selecionados se fossem mencionadas anomalias dentárias nos diferentes padrões de maloclusão esquelética. Foi adotado um conjunto de critérios para elegibilidade do estudo, com base na estratégia PECOS (População: maxila e mandíbula; Exposição: discrepâncias esqueléticas; Comparação: padrão de normalidade; e Resultado: anomalias dentárias). Cinco estudos retrospectivos contendo 7679 participantes foram classificados e considerados elegíveis para a revisão sistemática. A amostra do estudo II foi composta por 20 participantes. As coletas foram realizadas com intervalo de no mínimo um dia entre elas e foram armazenadas a -20°C até a extração do DNA ser realizada (Qiagen®). O estudo III foi composto por uma amostra de 505 registros ortodônticos. Dezenove pontos cefalométricos, serviram para a obtenção dos ângulos e medidas utilizados para a caracterização esquelética, utilizando-se o Software Dolphin. Amostras de saliva foram coletadas de todos os participantes e o DNA foi extraído, diluído e quantificado. Os genes TGFA, IRF6 e MSX1 foram usados para reações de PCR em tempo real. Os testes Razão de chance, Qui-quadrado, Exato de Fisher, T independente e coeficiente de correlação (nível de significância = 95%) foram realizados. A partir da revisão sistemática, concluiu-se que indivíduos com padrões de maloclusão esquelética têm mais anomalias dentárias. Após a análise estatística, não foi observado dimorfismo sexual em relação à concentração de DNA (p = 0,76), idade (p = 0,91) e etnias (p = 0,72). Não houve diferença significativa entre os métodos de coleta em relação à quantidade e pureza do DNA extraído (p≥0,05). O gene IRF6 foi associado com a ME Classe III (p = 0,04, OR = 0,69, IC 0,49-0,98) e o gene MSX1 foi associado ao padrão de crescimento hipodivergente (p=0,003, OR=0,5, IC 0,36-0,74) e ME Classe II (p=0,0001, OR=0,6, IC 0,46-0,78). Em relação a AD, o gene MSX1 também foi associado à impactação (p=0,03, OR=0,67, IC 0,47-0,96) e dilaceração (p=0,04, OR=0,27, IC 0,07-0,977). MSX1 associouse ao padrão de crescimento hipodivergente e Classe II, e impactação e dilaceração, mostrando que existe uma associação genética entre anomalias dentárias e maloclusões esqueléticas. (AU)

The objective of the present study was to verify the phenotype-genotype association between TGFA (Transforming Growth Factor α) (C/T rs1523305), IRF6 (Interferon Regulatory Factor 6) (A/C rs2013162) and MSX1 (Muscle Segment Homeobox 1) (A/G rs12532) and dental anomalies in patients with skeletal malocclusion. Two previous studies were carried out with the objective of (I) to determine if individuals with Class II or III skeletal discrepancies present a higher frequency of dental anomalies compared to individuals with Class I malocclusion and (II) to compare four different types of saliva and oral buccal cell collecting methods for genomic DNA extraction: (1)Expectoration of saliva, (2)Expectoration of saliva with lingual stimulation, (3)Scraping with cytological brush, and (4)Scraping with cytological brush and expectoration of saliva, evaluating its concentration and purity. In the systematic review, a search of the main electronic medical scientific literature databases was conducted. Observational studies were selected if mentioning dental anomalies in the different skeletal malocclusion patterns. A set of criteria for the eligibility of the study was adopted, based on the PECOS strategy (Population: maxilla and mandible, Exposure: skeletal discrepancies, Comparison: normality pattern, and Outcome: dental anomalies). Five retrospective studies containing 7679 participants were classified and considered eligible for the systematic review. The sample of study II was composed by 20 participants. The biological samples were collected at intervals of at least one day between them and were stored at -20 ° C until DNA extraction was performed (Qiagen®). Study III was composed of a sample of 505 orthodontic records. Nineteen cephalometric points were used to obtain the angles and measurements used for the skeletal characterization, using Dolphin Software. Saliva samples were collected from all participants and the DNA was extracted, diluted and quantified. The TGFA, IRF6 and MSX1 genes were used for real-time PCR reactions. The odds ratio, chi-square, Fisher's exact, independent T and correlation coefficient (significance level = 95%) tests were performed. From the systematic review, it was concluded that individuals with skeletal malocclusion patterns have more dental anomalies. After the statistical analysis, no sexual dimorphism (p = 0.76), age (p = 0.91) and ethnicity (p = 0.72) was observed in relation to DNA concentration. There was no significant difference between the collection methods in relation to the amount and purity of the extracted DNA (p≥0.05). IRF6 was associated with Class III skeletal malocclusion (p=0.04, OR=0.69, C.I. 0.49-0.98), and MSX1 was associated with hypodivergent growth pattern (p=0.003, OR=0.5, 95% C.I. 0.36-0.74), and Class II skeletal malocclusion (p=0.0001, OR=0.6, C.I. 0.46-0.78). In regards to dental anomalies, MSX1 was also associated with tooth impaction (p=0.03, OR=0.67, 95% C.I. 0.47-0.96) and root dilaceration (p=0.04, OR=0.27, 95% C.I. 0.07-0.97). MSX1 was associated with both hypodivergent growth pattern and Class II skeletal malocclusion (p=0.0001), and tooth impaction (p=0.03) and root dilaceration (p=0.04), whereas IRF6 was associated with Class III skeletal malocclusion, (AU)

El objetivo del presente estudio fue verificar la presencia de asociación fenotipo-genotípica entre TGFA (Factor de crecimiento transformante α) (C / T rs1523305), IRF6 (Factor regulador de interferón 6) (A / C rs2013162) y MSX1 (Segmento muscular 1 de Homeobox 1). ) (A / G rs12532) y anomalías dentales en pacientes con malclusión esquelética. Con este fin, se realizaron dos estudios previos para (I) determinar si las personas con discrepancias esqueléticas de Clase II o III tienen una mayor frecuencia de anomalías dentales en comparación con las personas con maloclusión de Clase I y (II) para comparar cuatro métodos diferentes. y colección de células salivales [Esputo de saliva (1), Estímulo lingual Saliva Esputo (2), Raspado con cepillo citológico (3) y Raspado con cepillo citológico más Esputo de saliva (4)] para extracción de ADN genómico , evaluando su concentración y pureza. En la revisión sistemática, buscamos en las principales bases de datos de la literatura científica médica electrónica. Se seleccionaron estudios de observación si se mencionaban anomalías dentales en los diferentes patrones de maloclusión esquelética. Se adoptó un conjunto de criterios para la elegibilidad del estudio, basado en la estrategia PECOS (Población: maxilar y mandíbula; Exposición: discrepancias esqueléticas; Comparación: patrón de normalidad; y Resultado: anomalías dentales). Cinco estudios retrospectivos con 7679 participantes fueron clasificados y considerados elegibles para una revisión sistemática. La muestra del estudio II consistió en 20 participantes. Se tomaron muestras con al menos un día de diferencia y se almacenaron a -20 ° C hasta que se realizó la extracción de ADN (Qiagen®). El estudio III consistió en una muestra de 505 registros de ortodoncia. Diecinueve puntos cefalométricos se utilizaron para obtener los ángulos y las medidas utilizadas para la caracterización esquelética utilizando Dolphin Software. Se recogieron muestras de saliva de todos los participantes y se extrajo, diluyó y cuantificó el ADN. Los genes TGFA, IRF6 y MSX1 se usaron para reacciones de PCR en tiempo real. Se realizaron las pruebas de odds ratio, Chi-cuadrado, exacta de Fisher, T independiente y coeficiente de correlación (nivel de significancia = 95%). De la revisión sistemática, se concluyó que las personas con patrones de maloclusión esquelética tienen más anomalías dentales. Después del análisis estadístico, no se observó dimorfismo sexual en relación con la concentración de ADN (p = 0,76), la edad (p = 0,91) y el origen étnico (p = 0,72). No hubo diferencias significativas entre los métodos de recolección con respecto a la cantidad y pureza del ADN extraído (p≥0.05). El gen IRF6 se asoció con ME Clase III (p = 0.04, OR = 0.69, CI 0.49-0.98) y el gen MSX1 se asoció con el patrón de crecimiento hipodivergente (p = 0.003, OR = 0.5, CI 0.36-0.74) y EM Clase II (p = 0.0001, OR = 0.6, CI 0.46-0.78). Con respecto a AD, el gen MSX1 también se asoció con impactación (p = 0.03, OR = 0.67, CI 0.47-0.96) y laceración (p = 0.04, OR = 0.27, IC 0,07-0,977). MSX1 se asoció con un patrón de crecimiento hipodivergente y de Clase II, impactación y laceración, lo que demuestra que existe una asociación genética entre las anomalías dentales y las maloclusiones esqueléticas. (AU)

A successful dental management in a child with Cornelia de Lange Syndrome: rare case of Cornelia de Lange Syndrome in child / O sucesso do manejo odontológico em criança com Síndrome Cornelia de Lange: um caso raro da Síndrome Cornelia de Lange em criança

Background: the Cornelia de Lange Syndrome (CDLs) is a rare and complex syndrome characterized, basically, by psychomotor retardation associated with a number of congenital malformations. Aims: this paper reports the case of an 11-year-old female child diagnosed with Cornelia de Lange Syndrome (CdLS) and her successful dental management. Case report: the patient had severe mental retardation, definite negative behavior and the clinical findings included oral and physical changes. The patient's oral hygiene was deficient with the presence of calculus and gingivitis, besides several active caries lesions in permanent and deciduous dental elements. The treatment consisted in guidance for caregivers about oral hygiene and diet, and the dental procedures were performed under general anesthesia. Currently, the patient is accompanied by monthly follow-ups. Conclusions: the lack of knowledge about oral hygiene and cariogenic diets was identified as a one of the reasons for the oral diseases present. Due to the need to care for the other more serious and complex health problems, the oral diseases had evolved faster than usual and thus were difficult to treat and maintain thereafter. Under such conditions, the dentist plays a key role within a multidisciplinary team. From the guidance and knowledge provided in the dental clinic, there was a significant improvement in the life quality of the child and her family

Third molar agenesis as a potential marker for craniofacial deformities.

The identification of clinical patterns of tooth agenesis in individuals born with craniofacial deformities may be a useful tool for risk determination of these defects. We hypothesize that specific craniofacial deformities are associated with third molar agenesis. OBJECTIVE: The aim of this study was to identify if third molar agenesis could have a relation with other craniofacial structure alterations, such as cleft lip and palate, skeletal malocclusion, or specific growth patterns in humans. DESIGN: Data were obtained from 550 individuals ascertained as part of studies aiming to identify genetic contributions to oral clefts. 831 dental records of patients aged over eight years seeking orthodontic treatment were also included. SN-GoGn angle were used to classify the growth pattern (hypo-divergent, normal and hyper-divergent), and the ANB angle was used to verify the skeletal malocclusion pattern (Class I, II and III). Panoramic radiographs were used to determine third molar agenesis. RESULTS: A high frequency of third molar agenesis among individuals born with cleft lip with or without cleft palate (55%), as well as among their relatives (93.5%) was found. Third molar agenesis was not associated to skeletal malocclusion or growth pattern. CONCLUSION: It appears that third molar agenesis is associated with the disturbances that lead to cleft lip and palate.

Dental anomalies in different growth and skeletal malocclusion patterns.

OBJECTIVES: To evaluate prevalence, distribution, and sexual dimorphism of dental anomalies (DA) among different skeletal malocclusions (SM) and growth patterns (GP) under the hypothesis that specific clinical patterns exist and may indicate common etiological roots. MATERIALS AND METHODS: A total of 1047 orthodontic records of patients older than 8 years were evaluated. The SN-GoGn angle was used to classify GP (hypodivergent, normal, and hyperdivergent), and the ANB angle was used to verify SM (Angle Classes I, II, and III). These assessments were done from lateral cephalometric radiographs. DA were diagnosed using panoramic radiographs by one calibrated investigator. Odds ratios, chi-square, and Student's t-tests were used. RESULTS: Of the subjects, 56.7% were female, with mean age of 16.41 (±10.61) years. The prevalence of DA was 15.7%. Impaction and tooth agenesis were the most prevalent DA, with relative frequencies of 14.4% and 9.7%, respectively. DA were most prevalent in Class III SM (80.8%) and in hypodivergent GP (82.5%), although this was not statistically significant. Tooth agenesis ( P < .01) and microdontia ( P = .025) were significantly more common among hypodivergent GP and Class III SM, respectively. CONCLUSIONS: The results of this study support the idea that DA are preferentially associated with certain patterns of malocclusion.

Anomalias Dentárias em Pacientes Portadores de Maloclusão Esquelética: um Estudo Epidemiológico / Dental anomalies in patients with skeletal malocclusion: an epidemiological study

O objetivo do presente estudo censitário foi avaliar a prevalência das anomalias dentárias (AD) e a sua possível associação com os diferentes padrões de crescimento facial (PCF) e as maloclusões esqueléticas (ME) em uma população ortodôntica. Para tanto, 1521 prontuários ortodônticos de todos os pacientes atendidos, no período de 2000 a 2013, nos Departamentos de Ortodontia de duas instituições de ensino de referência na cidade do Rio de Janeiro, Brasil, foram avaliados. Foram excluídos (n=474) os prontuários que não continham ambas as radiografias (panorâmica e cefalométrica de perfil), pacientes com idade inferior a 08 anos e presença de síndrome, fissura lábio/palatina e desequilíbrios metabólicos e/ou endócrinos. Através da radiografia cefalométrica de perfil, o ângulo SnGoGn foi obtido para verificar o PCF (Hipodivergente, Normal e Hiperdivergente) e o ângulo ANB, para classificar as ME (Classe I, II e III). Os diagnósticos das AD foram realizados na radiografia panorâmica por um único operador calibrado. Para o diagnóstico de agenesia de terceiros molares (3M), foram excluídos (n=216) os pacientes cuja confirmação de extração destes dentes não foi possível. A frequência e a porcentagem de cada AD foram calculadas. As variáveis gênero, etnia, AD e dente mais afetado foram testadas através dos Testes QuiQuadrado e Exato de Fisher com nível de significância de 5%. A Razão de Chance foi realizada para avaliação da intensidade e direção das possíveis associações. Além disso, o Teste T-Student foi utilizado para comparar diferenças entre os grupos. A amostra final foi composta por 1047 pacientes e a prevalência de AD foi de 77%. Do total, 56,7% eram do gênero feminino e 64,9%, afrodescendentes, com média de idade de 16,41 (±10,61). As AD mais prevalentes foram impactação (68,6%), giroversão (54%) e agenesia (9,7%), excluindo os 3M, respectivamente. Além disso, observou-se uma media de 3,08 (±1,93) dentes afetados por paciente e 51,2% apresentaram mais de uma AD. Dentre os 831 pacientes incluídos no diagnóstico de presença ou ausência de 3M, 11,2% apresentaram agenesia de 3M e 75,3% apresentaram outra AD, fora a agenesia de 3M. O 3M inferior esquerdo foi o dente mais afetado na impactação, o canino inferior direito, na giroversão e o incisivo lateral superior direito foi o dente mais ausente, excluindo os 3M. As AD foram mais prevalentes na ME de Classe III (80,8%) e no PCF Hipodivergente (82,5%). Agenesia de outros dentes, excluindo os 3M, apresentou associação com o PCF Hipodivergente (p<0,01) e a microdontia, com a ME de Classe III (p=0,25). A agenesia de 3M apresentou associação com agenesia de outros dentes, microdontia e associação inversa com impactação (p<0,01). As AD apresentaram alta prevalência e devem ser cuidadosamente investigadas e consideradas no planejamento do tratamento ortodôntico. (AU)

The aim of this census study was to evaluate the prevalence of dental anomalies (DA) and its possible association with the different skeletal malocclusion (SM) and growth patterns (GP) in an orthodontic population. For this study, 1521 orthodontic records of all patients attended, in the period of 2000 to 2013, in the Departments of Orthodontics of two reference institutions in the city of Rio de Janeiro, Brazil, were evaluated. The records that did not contain both radiographs (panoramic and lateral cephalometric), patients younger than 08 years old and presence of syndrome, cleft lip/palate, metabolic and/or endocrine imbalances were excluded. Sn-GoGn angle was obtained to verify the GP (Hypo-divergent, Normal and Hyper-divergent) and the ANB angle, to classify SM (Class I, II and III) in lateral cephalometric radiograph. DA diagnosis were performed on panoramic radiographs by a single calibrated operator. For the diagnosis of third molars (3M) agenesis, patients whose confirmation of extraction of these teeth was not possible were excluded (n=216). The frequency and percentage of each DA were calculated. The gender, ethnicity, age, DA and more affected tooth variables were tested using the Chi-Square and Fisher Exact Testes with significance level of 5%. The Odds Ratio was performed to evaluate the intensity and direction of the associations. Additionally, the Student T-test was used to compare differences between groups. The final sample was consisted of 1047 patients and the prevalence of DA was 77%. From a total, 56.7% were female and 64.9%, African descent, with a mean age of 16.41 (±10.61). The most prevalent DA were impaction (68.6%), giroversion (54%) and agenesis (9.7%), excluding 3M, respectively. Furthermore, we observed an average of 3.08 (± 1.93) teeth affected per patient and 51.2% had more than one DA. Among the 831 patients included in the diagnosis of the presence or absence of 3M, 11.2% had 3M agenesis and 75.3% had another DA, apart from 3M agenesis. The lower left 3M was the most affected tooth in impaction, the lower right canine, in giroversion and the upper left lateral incisor was the most absent tooth, excluding 3M. The DA were more prevalent in Class III SM (80.8%) and in the Hypo-divergent GP (82.5%). Agenesis of other teeth, excluding 3M, was associated with the Hypo-divergent GP (p <0.01) and microdontia, with the Class III SM (p=0.25). 3M agenesis was associated with agenesis of other teeth, microdontia and impaction (p<0.01). AD had a high prevalence and must be carefully investigated and considered in orthodontic treatment planning. (AU)