Dissertations / Theses on the topic 'Craniofacial syndromes'

As anomalias craniofaciais ocasionam comprometimentos estéticos e funcionais com grande impacto na saúde e na integração social da criança, com interferência no desenvolvimento global e social. Das anomalias craniofaciais este estudo abordou as Fissuras Labiopalatinas (FLP) e o Espectro Óculo Aurículo Vertebral (EOAV). As FLP constituem malformações resultantes de falta do fechamento completo dos tecidos que compõe o lábio e o palato. O EOAV, também conhecido como Síndrome de Goldenhar, é uma anomalia congênita de etiologia desconhecida, com manifestação genética variável e de causa bastante heterogênea. Conhecer as habilidades funcionais e o impacto destas no desenvolvimento global de crianças com EOAV e FLP pode otimizar o desenvolvimento de programas de prevenção e intervenção para promover a saúde e a integração social destes indivíduos. Este estudo foi delineado com objetivo de verificar e comparar o desempenho em habilidades funcionais quanto ao desempenho nas áreas de autocuidado, mobilidade, função social e nível de independência entre crianças com EOAV, crianças com FLP e um grupo comparativo, de crianças sem anomalias. O modelo de pesquisa foi observacional descritivo transversal com uma casuística de 39 pais/responsáveis de crianças na faixa etária entre três anos e sete anos e seis meses, de ambos os gêneros. Foram convidados para participar pais/responsáveis de crianças em tratamento no Hospital de Reabilitação de Anomalias Craniofaciais da Universidade e São Paulo (HRAC-USP) os quais foram divididos em três grupos: dois experimentais e um grupo comparativo. O instrumento para coleta dos dados das habilidades funcionais foi o Pediatric Evaluation of Disability Inventory (PEDI), em sua versão adaptada para o português. A avaliação é realizada por meio de entrevista com o cuidador, o qual deve saber informar sobre o desempenho da criança em atividades e tarefas típicas da rotina diária. Os dados foram apresentados por análise descritiva com medidas de tendência central (média aritmética), dispersão (desvio-padrão) e distribuição de frequência, nas variáveis: idades, gênero e nível socioeconômico da família e caracterização da casuística. Para as análises das pontuações bruta e normativa do questionário PEDI no que se refere às habilidades funcionais e a assistência do cuidador nas três áreas de função autocuidado, mobilidade e função social, foi utilizado o teste de variância One Way, e para o teste de normalidade foi utilizado Shapiro Wilk para variável dependente. A análise comparativa foi realizada pelo teste de Kruskal-Wallis, adotando-se o valor de significância de p< 0,05. Os resultados deste estudo na análise comparativa nas habilidades funcionais na mobilidade, houve diferença estatisticamente significante na comparação entre os grupos GC vs GEEOAV, no escore bruto, e entre os grupos GC vs GEEOAV e GC vs GEFLP, no escore normativo.Na assistência do cuidador no autocuidado, houve diferença estatisticamente significante na comparação entre os grupos GC vs GEEOAV, no escore normativo. Na assistência do cuidador na mobilidade, houve diferença estatisticamente significante na comparação entre os grupos GC vs GEEOAV nos escores bruto e normativo.Na assistência do cuidador na função social houve diferença estatisticamente significante na comparação entre os grupos GC vs GEFLP.
Craniofacial anomalies cause aesthetic and functional impairments with major impact on health and social integration of children with interference in global and social development. Craniofacial anomalies of this study addressed the cleft lip and palate (CLP) and the Spectrum goggles Atrium Vertebral (OAVS). The FLP constitute defects resulting from lack of complete closure of the tissues that make up the lip and the palate. The OAVS, also known as Goldenhar syndrome is a congenital anomaly of unknown etiology, with genetic variable manifestation and cause very heterogeneous. Knowing the functional abilities and their impact on the overall development of children with OAVS and FLP can optimize the development of prevention and intervention programs to promote health and social integration of individuals. This study was designed in order to verify and compare the performance of functional skills in performance in the areas of self-care, mobility, social function and level of independence among children OAVS, children with CLP and a comparison group of children without defects. The research model was crosssectional observational with a sample of 39 parents / guardians of children aged between three and seven years and six months, of both genders. Were invited to attend parent / guardians of children undergoing treatment at the Craniofacial Anomalies Rehabilitation Hospital of the University and São Paulo (HRAC-USP) were divided into three groups: two experimental and comparison group. The instrument for data collection of functional abilities was the Pediatric Evaluation of Disability Inventory (PEDI), in its version adapted to Portuguese. The evaluation is carried out through interviews with the caregiver, which should know to report on the performance of the child in typical activities and tasks of daily routine. The data were presented by descriptive analysis with measures of central tendency (arithmetic mean), dispersion (standard deviation) and frequency distribution, the variables: age, gender and socioeconomic status of the family and characterization of the series. For the analysis of raw scores and rules of ask questionnaire with regard to the functional skills and caregiver assistance in three areas of self-care function, mobility and social function, One Way variance test was used, and the normality test Shapiro Wilk was used for dependent variable. The comparative analysis was performed using the Kruskal-Wallis test, adopting the significance p value <0.05. The results of this study in comparative analysis on functional mobility skills, there was a statistically significant difference when comparing the GC vs GEEOAV groups in the raw score, and between the GC and GC vs vs GEEOAV GEFLP groups in normativo.Na score caregiver assistance self-care, there was a statistically significant difference when comparing the GC vs GEEOAV groups, the score normativo.Na caregiver assistance in mobility, there was a statistically significant difference when comparing the GC vs GEEOAV groups in the raw scores and normativo.Na caregiver assistance social function was no statistically significant difference when comparing the GC vs GEFLP groups.

Este estudo investigou a prevalência de disgenesias dentárias, alterações de tecido mole e características cefalométricas em pacientes com síndrome velocardiofacial e síndrome G/BBB. A presença de disgenesias dentárias foi avaliada em pacientes acima de seis anos de idade; para a análise cefalométrica, foram avaliadas telerradiografias laterais obtidas antes de qualquer intervenção ortodôntica. A amostra de estudo para a síndrome velocardiofacial incluiu 26 pacientes para análise de disgenesias dentárias e alterações de tecido mole e 18 pacientes para análise cefalométrica. Para a síndrome G/BBB, foram analisados 21 pacientes quanto à presença de disgenesias dentárias e alterações de tecido mole, e 23 pacientes para a análise cefalométrica. Foram incluídos apenas pacientes de etnia branca. A ocorrência de agenesias dentárias e dentes supranumerários foi comparada a pacientes sem nenhuma alteração morfofuncional, pareados para gênero e idade. Para a análise cefalométrica, as telerradiografias foram traçadas manualmente; os traçados foram digitalizados e as variáveis foram medidas com auxílio do software Dentofacial Planner 7.0. Nesta análise, os pacientes também foram comparados a pacientes sem nenhuma alteração morfofuncional, pareados para gênero e idade. Para a síndrome velocardiofacial, 76,92% dos pacientes apresentaram pelo menos uma disgenesia dentária, com predominância de alterações hipoplasiantes, principalmente representadas por hipodesenvolvimento da cúspide lingual do primeiro pré-molar inferior e opacidades de esmalte; a ocorrência de agenesias dentárias e dentes supranumerários foi semelhante à observada no grupo controle. Na análise cefalométrica, observou-se menor comprimento da base do crânio (total e da parte posterior); retrusão e redução da altura posterior da maxila; aumento do ângulo goníaco; aumento do ângulo interincisal; maior inclinação lingual dos incisivos inferiores; redução do ângulo nasolabial; e redução da profundidade nasal, comparado ao grupo controle. Com relação à síndrome G/BBB, 95,23% dos pacientes apresentaram pelo menos uma disgenesia dentária, com predominância de alterações hipoplasiantes; a freqüência de agenesias dentárias e dentes supranumerários foi significativamente maior comparada ao grupo controle. Foi observada anquiloglossia em 11 de 21 pacientes. A análise cefalométrica revelou aumento do ângulo da base do crânio; maior retrusão dos ossos nasais; encurtamento do ramo, redução do comprimento, e retrusão da mandíbula; maior discrepância maxilomandibular, com maior convexidade facial; maior inclinação lingual dos incisivos inferiores e superiores; padrão de crescimento mais vertical; nariz mais achatado, ponte nasal mais curta, maior retrusão nasal e redução da profundidade nasal, comparado ao grupo controle. Em conclusão, na avaliação de pacientes com hipótese diagnóstica das referidas síndromes, sugere-se investigar a anatomia oclusal de pré-molares inferiores no caso da síndrome velocardiofacial, e a presença de dentes supranumerários anteriores inferiores e anquiloglossia para a síndrome G/BBB. A análise cefalométrica também indicou diferenças significativas em diversas variáveis, simultaneamente servindo como parâmetro na descrição das síndromes e exigindo protocolo de tratamento diferenciado para estes pacientes.
This study investigated the prevalence of tooth abnormalities, soft tissue changes and cephalometric analysis in patients with velocardiofacial syndrome and G/BBB syndrome. The presence of tooth abnormalities was evaluated in patients older than six years; cephalometric analysis was conducted on lateral cephalograms obtained before any orthodontic intervention. The study sample for the velocardiofacial syndrome included 26 patients for analysis of tooth abnormalities and soft tissue changes, and 18 patients for cephalometric analysis. For the G/BBB syndrome, 21 patients were analyzed as to the presence of tooth abnormalities and soft tissue changes, and 23 patients for cephalometric analysis. Only white patients were included. The occurrence of tooth abnormalities and supernumerary teeth was compared to patients without any morphofunctional alterations, matched for gender and age. For cephalometric analysis, the lateral cephalograms were manually traced; tracings were digitized and the variables were measured on the software Dentofacial Planner 7.0. For this analysis, patients were also compared to individuals without malformations, matched for gender and age. For the velocardiofacial syndrome, 76.92% of patients presented at least one tooth abnormality, with predominance of hypoplastic alterations, especially represented by hypodevelopment of the lingual cusp of mandibular first premolars and enamel opacities; the occurrence of tooth agenesis and supernumerary teeth was similar to that observed in the control group. Cephalometric analysis revealed reduced length of the skull base (total and of the posterior portion); retrusion and reduction of posterior height of the maxilla; increased gonial angle; increased interincisal angle; greater lingual inclination of mandibular incisors; reduced nasolabial angle; and reduced nasal depth, compared to the control group. Concerning the G/BBB syndrome, 95.23% of patients presented at least one tooth abnormality, with predominance of hypoplastic alterations; the frequency of tooth agenesis and supernumerary teeth was significantly higher compared to the control group. Ankyloglossia was observed in 11 of 21 patients. Cephalometric analysis revealed increased cranial base angle; greater retrusion of nasal bones; shortening of mandibular ramus, reduced mandibular length, and mandibular retrusion; greater maxillomandibular discrepancy, with greater facial convexity; greater lingual inclination of maxillary and mandibular incisors; more vertical growth pattern; more flattened nose, shorter nasal bridge, greater nasal retrusion and reduced nasal depth, compared to the control group. In conclusion, during evaluation of patients with suspected diagnosis of the syndromes, investigation of the occlusal anatomy of mandibular premolars in case of velocardiofacial syndrome, and of the presence of mandibular anterior supernumerary teeth and ankyloglossia for the G/BBB syndrome are suggested. Cephalometric analysis also indicated significant differences in several variables, simultaneously serving as parameter for description of syndromes and requiring a customized treatment protocol for these patients.

A Síndrome de Apert é caracterizada por craniossinosteses e sindactilia dos dedos das mãos e dos pés. Essas malformações causam diminuição do crescimento da base do crânio com hipoplasia da face associada a severa retrusão maxilar e podem impor um imenso sofrimento tanto à função quanto à estética da pessoa afetada. O tratamento inclui vários procedimentos cirúrgicos que são adaptados às necessidades do indivíduo afetado. O objetivo desse estudo foi avaliar a morfologia craniofacial e os arcos dentários de adolescentes e adultos jovens com Síndrome de Apert comparando-os com um grupo controle. Foram avaliados 22 indivíduos que foram submetidos ao exame de tomografia computadorizada de feixe cônico (TCFC) para avaliação e diagnóstico e também foram obtidos modelos digitalizados. A amostra foi composta por um grupo de estudo (G1) e um grupo controle (G2). No grupo G1 foram incluídos 11 indivíduos com síndrome de Apert com idade entre 11 e 22 anos. No grupo G2 foram incluídos indivíduos pareados por gênero e idade ao grupo G1 e com equilíbrio das relações faciais e oclusão classe I. Foram realizadas medidas cefalométricas e análise de modelos no software Dolphin 3D para análise descritiva da norma frontal e lateral, formato da base craniana, análise estrutural dos componentes verticais e horizontais, tegumentos e dentes. Foram calculadas as correlações intraclasses para avaliação de concordância e a comparação entre os grupos foi aplicado o teste t de student, teste Mann-Whitney e o nível de significância adotado foi de 5%. Na comparação entre os grupos ,foram observadas diferenças significativas (p <= 0,05) , sendo que o grupo do indivíduos com síndrome de Apert apresentaram aumento da altura facial inferior, rotação horária da mandíbula associada a maior inclinação do corpo e ramo da mandíbula, ângulo da base do crânio diminuído, alteração entre a porção posterior e média da face, porém não existem muitas compensações dentárias, mas a maxila apresentou-se com dimensões menores que os indivíduos não sindrômicos .
Apert syndrome is characterized by craniosynostosis and syndactyly of the fingers and toes. These malformations cause a decrease in the growth of the skull base with facial hypoplasia associated with severe maxillary retrusion and can impose immense suffering on both the function and the aesthetics of the affected person. The treatment includes several surgical procedures that are tailored to the needs of the affected individual. The aim of this study was to evaluate the craniofacial morphology and dental arches of adolescents and young adults with Apert\'s Syndrome comparing them with a control group. Twenty-two patients who underwent concomitant computed tomography (CBCT) examination and evaluation were evaluated. The sample consisted of one study group (G1) and one control group (G2). In the G1 group, 11 individuals with Apert syndrome were included between 11 and 22 years of age. In the G2 group, individuals were paired by gender and age to the G1 group and with balance of facial relations and class I occlusion. Cephalometric measurements and model analysis were performed in Dolphin 3D software for descriptive analysis of frontal and lateral norm, cranial base shape, structural analysis of vertical and horizontal components, integuments and teeth. Intraclass correlations were calculated for concordance evaluation and the comparison between the groups was applied the t student test, Mann-Whitney test and the level of significance was 5%. In the comparison between the groups, significant differences were observed (p <= 0.05), and the group of individuals with Apert syndrome presented lower facial height increase, hourly rotation of the mandible associated with greater inclination of the body and branch of the mandible, decreased cranial base angle, favoring a more vertical position, there was alteration between the posterior and middle portion of the face, however there are not many dental compensations, but the maxilla presented smaller dimensions than the non-syndromic individuals that can favor several alterations dental changes.

Neste trabalho, estudamos duas malformações craniofaciais mendelianas, decorrentes de um distúrbio do desenvolvimento dos primeiro e segundo arcos faríngeos: a síndrome de Treacher Collins (STC) e a síndrome Aurículo-condilar (SAC). A identificação de genes e de mecanismos moleculares associados a essas condições, além de contribuir para a compreensão do desenvolvimento das estruturas derivadas desses arcos faríngeos, é fundamental para o desenvolvimento do diagnóstico molecular, uma ferramenta importante para diagnóstico diferencial e aconselhamento genético. Contribuímos para uma melhor caracterização clínica da SAC com a descrição de uma nova família com 11 afetados. Após excluirmos quatro genes/regiões candidatas para síndromes de 1º e 2º arcos faríngeos, realizamos estudos de ligação usando marcadores polimórficos ao longo do genoma. Mapeamos o primeiro lócus associado à SAC, 1p21.1-q23.3 (lod score=3.0), e nossos dados sugerem que há heterogeneidade genética para essa patologia. Com relação ao estudo da STC, realizamos uma extensa revisão da nomenclatura das mutações patogênicas descritas na literatura, além de investigar mecanismos mutacionais atípicos na STC, corroborando a hipótese de que mutações nos exons que sofrem splicing alternativo são capazes de gerar o fenótipo da síndrome. Demos continuidade à caracterização do espectro de mutações no gene TCOF1 e investigamos a correlação genótipo-fenótipo numa amostra de 58 pacientes com STC. A análise dos dados de polimorfismos da região codificadora do gene permitiu que fizéssemos inferências sobre o regime de seleção ao qual o TCOF1 está submetido, e os resultados sugeriram que o gene TCOF1 está sob seleção purificadora, que atua sobre mutações fracamente deletérias. Também inferimos a fase para um conjunto de polimorfismos da região codificadora, verificando se havia associação de algum haplótipo à gravidade do quadro clínico ou à predisposição para a doença. Dada a observação de ausência de correlação haplótipo/genótipo-fenótipo, testamos a hipótese de que variações nos níveis de expressão do alelo normal poderiam ser responsáveis pela variabilidade clínica observada nos pacientes portadores da STC. Para tanto, iniciamos o estudo funcional das regiões regulatórias do gene TCOF1 , inclusive, de regiões distantes do promotor mínimo, preditas como enhancers. Identificamos polimorfismos em sua região promotora, sendo um deles capaz de diminuir os níveis de transcrição e de afetar a ligação do fator de transcrição YY1 ao promotor do TCOF1 . Caracterizamos a ação de YY1 como repressora in vitro. Testamos também a hipótese de haploinsuficiência como mecanismo associado à STC. Quantificamos os níveis de transcritos do TCOF1 em indivíduos afetados e normais e observamos uma diferença significativa. Nosso trabalho corrobora a hipótese de haploinsuficiência e mostra pela primeira vez que pacientes têm degradação de transcritos. Também investigamos a possibilidade de os níveis de transcritos estarem correlacionados à variabilidade fenotípica. Comparamos os dados de expressão de cada paciente à freqüência de nove sinais clínicos principais da STC, mas nenhuma correlação foi observada. Investigamos o padrão de metilação da ilha CpG do gene TCOF1 em pacientes e em controles, com o intuito de verificar se diferentes níveis de metilação inter-individual estariam associados à grande variação na expressão gênica. Demonstramos que a metilação da ilha CpG não é o mecanismo regulatório por trás dessa ampla variação de expressão do TCOF1
In the present study, we investigate two craniofacial mendelian disorders, resulting from abnormalities in the development of the first and second pharyngeal arches: the Treacher Collins Syndrome (TCS ) and the auriculo condylar syndrome (ACS). The identification of genes and molecular mechanisms associated to these conditions, in addition to contributing to the understanding of the development of structures derived from these pharyngeal arches, is fundamental for the development of molecular diagnostics, an important tool for differential diagnosis and genetic counseling. We contributed to a better clinical characterization of ACS with a description of a new family with 11 affected individuals. After excluding four candidate genes/regions for syndromes of the 1st and 2nd pharyngeal arches, we carried out linkage studies using polymorphic markers throughout the genome. We mapped the first locus associated to ACS, 1p21.1-q23.3 (lod score=3.0), and our data suggest genetic heterogeneity exists for this pathology. With respect to the study of TCS , we carried out an extensive review of the nomenclature for the pathogenic mutations described in the literature, in addition to investigating atypical mutation mechanisms in TCS , corroborating the hypothesis that mutations in the exons that undergo alternative splicing can result in the TCS phenotype. We continued the characterization of the mutation spectrum for TCOF1 and we investigated the genotype-phenotype correlation in a sample of 58 patients with TCS . The analysis of polymorphisms in the coding region allowed us to make inferences about the selective regime experienced by TCOF1 , and our results suggested that TCOF1 is under purifying selection, which acts upon weakly deleterious mutations. We also inferred the phase for a set of polymorphisms in the coding region, testing whether there was association between any haplotype and the severity of the phenotype or the susceptibility to the disease. Given the observation of no correlation between haplotype/genotype and phenotype, we tested the hypothesis that variation in the levels of expression of the normal allele could be responsible for the clinical variability observed in TCS patients. To do this, we started a functional study of the TCOF1 regulatory regions, including regions distant from the minimal promoter, predicted to be enhancers. We identified polymorphisms in the promoter region, one of which reduced the levels of transcription and affected the binding of the YY1 transcription factor to the TCOF1 promoter. Using an in vitro assay we characterized YY1 as a repressor. We also tested the hypothesis of haploinsufficiency as a mechanism associated to TCS . We quantified the levels of TCOF1 transcripts in normal and affected individuals and found a significant difference. Our study corroborates the haploinsufficiency hypothesis and for the first time shows that patients have transcript degradation. We also investigated the possibility that transcripts levels are correlated to phenotypic variability. We compared the expression data for each patient with the frequency of nine clinical signs of TCS , but no correlation was found. We investigated the pattern of methylation on the CpG island of TCOF1 in patients and controls, in order to test whether different levels of methylation among individuals were associated to the great variation in gene expression. We demonstrated that methylation of the CpG island is not the regulatory mechanisms underlying the broad variation in TCOF1 expression.

Orientador: João Roberto Gonçalves
Resumo: O espectro oculoauriculovertebral (EOAV), também conhecido como Síndrome de Goldenhar, afeta o desenvolvimento de estruturas dos 1º e 2º arcos branquiais que envolvem alterações mandibulares, oculares, vertebrais, auriculares e estruturas extracranianas. A maioria dos estudos sobre o EOAV são relatos clínicos e aqueles com populações significativas são descrições fenotípicas. Os estudos que avaliaram a morfologia tiveram seus resultados limitados ao incluir indivíduos com envolvimento unilateral, bilateral, leve, moderado e grave, na mesma amostra. Dessa forma, os objetivos do presente estudo foram de caracterizar a morfologia craniofacial e da via aérea e suas possíveis correlações em uma amostra homogênea (n = 18) composta apenas por indivíduos com EOAV unilateral grave. A análise da via aérea foi realizada por meio do Software Dolphin Imaging®. Para avaliar a morfologia craniofacial, sete medidas morfométricas foram realizadas com Software Materialize Mimics®. Para comparar as variáveis das vias aéreas e morfométricas, foi utilizado um grupo controle pareado por idade e sexo. Pelo teste de Shapiro-Wilk, observou-se que 13 das 35 variáveis não apresentaram distribuição normal. O teste t de Student foi aplicado para as variáveis de distribuição normal e Mann-Whitney para aquelas sem distribuição normal. Comparando os grupos Controle e OAVS para medidas craniofaciais, 16 das 26 variáveis foram estatisticamente significantes e, para as medidas das vias aéreas, todas foram esta... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The Oculoauriculovertebral spectrum (OAVS), also known as Goldenhar Syndrome, affects the development of structures of the 1st and 2nd branchial arches that involve mandibular, ocular, vertebral, auricular changes, as well as extracranial structures. Most OAVS studies are clinical reports, and those with significant populations are phenotypic description. Studies that evaluated morphology had their results limited by including individuals with unilateral, bilateral, mild, moderate and severe involvement in the same sample. The objectives of this study were to characterize the craniofacial and airway morphology and its possible correlations in a homogeneous sample (n = 18) composed only of unilateral severe OAVS individuals. Airway analysis was performed using Dolphin Imaging® software. To evaluate craniofacial morphology, seven morphometric measurements were performed by Materialize Mimics® Software. To compare airway and morphometric variables, a control group matched by age and sex was used. Through the Shapiro-Wilk test, it was observed that 13 of the 35 variables did not have normal distribution. Student's t-test was applied for the normal distribution variables and Mann-Whitney for those without normal distribution. Comparing the Control and OAVS groups for craniofacial measurements, 16 of the 26 variables were statistically significant, and for airway measurements all were statistically significant except for the RG Area variable. Pearson and Spearman's correlation coef... (Complete abstract click electronic access below)
Mestre

Obstructive Sleep Apnoea/Hypopnoea Syndrome (OSAHS) syndrome is a relatively common condition caused by recurrent upper airway obstruction during sleep. At this time sleep laboratory overnight multi-channel polysomnography testing provides the ‘gold’ standard for OSAHS diagnosis and subsequent treatment. Evidence suggests that the discrepancy between demand and available resources is steadily widening. The development of alternative diagnostic methods would therefore appear to be a worthy goal, and indeed this subject has received a great deal of attention within the recent literature. Differences in cranio-cervico-facial morphology in the OSAHS subjects as compared to their ‘normal’ counterparts has been a consistent finding and more recent investigations have aimed to prove the existence of a relationship between cranio-cervico-facial morphology and severity of the OSAHS condition. Evidence has been equivocal, and although a number have been suggested a correlation, none have yet converted this into a tool of clinical diagnostic significance. In this present investigation, sixty five (65) lateral cephalometric radiographs of subjects who had been referred to Edinburgh Royal Infirmary Sleep Centre for polysomnographic testing were retrospectively selected at random. To determine the existence of any correlation between the cranio-cervico-facial morphology and OSAHS severity as measured by the Apnoea Hypopnoea Index (AHI), a number of anatomic reference planes and points were used.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
O objetivo dessa dissertação foi investigar as alterações temporomandibulares, craniofaciais e posturais associadas à respiração bucal, além de avaliar a relação entre sinais clínicos e sintomas de distúrbios respiratórios do sono (DRS) em escolares respiradores bucais, na faixa etária de 7 a 14 anos. Trata-se de um estudo caso-controle, com amostra de 147 escolares, sendo 73 com respiração bucal (RB) e 74 com respiração nasal (RN), avaliados através de anamnese, exame clínico e testes respiratórios. Os escolares diagnosticados como respiradores bucais responderam a um questionário sobre a autopercepção de sintomas de DRS na infância, com foco em problemas do sistema mastigatório, nasais e do sono. A presença de respiração bucal foi estatisticamente significativa para as seguintes alterações: ausência de selamento labial (OR= 29.70); desvio durante abertura da boca (OR= 24.63); palato atrésico (OR= 5.07); assimetria facial (OR= 5.06); índice de Mallampati III e IV (OR= 2.85); má oclusão Classe II (OR=2.67); hipertrofia de conchas nasais (OR= 2.19). Não houve diferença significativa entre os grupos para as alterações posturais. Nos escolares RB, problemas na ATM e acordar com dor de cabeça foram associados à má oclusão Classe II e à falta de selamento labial. Dor na nuca e torcicolo foram associados à sobremordida alterada e à anteriorização da cabeça. Problemas com o sono, sonolência diurna, acordar à noite, roncar e dormir de boca aberta foram associados à hipertrofia das tonsilas palatinas e ao índice de Mallampati obstrutivo. A chance de alterações temporomandibulares e craniofaciais ocorrerem em escolares com padrão de respiração bucal foi elevada. O aparecimento de sintomas de DRS na infância parece estar associado à persistência da respiração bucal e suas consequentes alterações craniofaciais, oclusais, posturais e nas vias aéreas superiores
The aim of this study was to investigate the temporomandibular, craniofacial and postural changes associated with mouth breathing and also evaluate the relationship between clinical signs and SDB symptoms in children 7 to 14 years of age. A case-control study with a sample of 147 children, 73 mouth breathers (MB) and 74 nasal breathers (NB), were evaluated by anamnesis, clinical examination and respiratory tests. The schoolchildren diagnosed as MB answered a questionnaire on self-perceived symptoms of SDB, focusing on the masticatory system, nasal and sleep problems. The presence of mouth breathing was statistically significant with the following changes: a lack of lip seal (OR=29.70), a deviation during the opening of the mouth (OR=24.63), an atresic palate (OR=5.07), a facial asymmetry (OR=5.06), an obstructive Mallampati scores (OR=2.85), a Class II malocclusion (OR=2.67) and a turbinate hypertrophy (OR=2.19). No significant difference in postural pattern was found between groups. In the MB group, TMJ problems and wake up with headache were associated with a Class II malocclusion and a lack of lip seal. Stiff neck or neck pain were associated with an altered overbite and a forward head position. Sleep problems, daytime sleepiness, waking at night, snoring and sleeping with the mouth open were associated with a tonsillar hypertrophy and obstructive Mallampati scores. The chances of occurrence of temporomandibular and craniofacial changes were high in the MB schoolchildren. The emergence of the SDB symptoms in childhood appears to be associated with the persistency of the mouth breathing and their consequent craniofacial, occlusal, postural and upper airway s abnormalities

Orofacial clefts are a heterogeneous group of craniofacial malformations that affect the lip and/or palate and represent the most common craniofacial birth defect in humans. In 30% of patients the cleft is accompanied by additional physical or cognitive abnormalities. Hundreds of these clefting syndromes have been described, many of which have Mendelian inheritance patterns. The most common of these is Van der Woude syndrome (VWS), caused by mutations in the transcription factor IRF6 (Kondo et al. 2002). The other 70% of patients lack additional features and are considered nonsyndromic. The etiology of nonsyndromic clefts is complex and involves the combined action of multiple genetic variants interacting with environmental factors. A common approach for identifying genetic risk factor for complex disorders such as nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the genome wide association study (GWAS). We pursued a locus on 1p22 shown to be associated with NSCL/P by Beaty et al. (2010). Through a combination of expression studies in a mouse model and mutation screening in NSCL/P patients, we identified ARHGAP29 as a novel gene for NSCL/P and the likely etiologic gene at this locus. We identified eight rare variants in NSCL/P patients absent in controls including a nonsense and a frameshift mutation. These rare variants are reminiscent of previous resequencing studies that reported rare coding mutations in 20 different candidate genes for NSCL/P. We reviewed these variants and compared them with variants found in over 7000 exomes from the 1000 Genomes Project (1kGP) and NHLBI Exome Sequencing Project (ESP) to identify the variants and genes most likely to contain etiologic rare variants. We found good support for a role for rare variants in NSCL/P, particularly for MSX1 and genes of the FGF signaling pathway. We next performed several studies to understand the genetic architecture of syndromic forms of clefting, focusing on VWS and popliteal pterygium syndrome (PPS), which is allelic to VWS. We compiled all of the nearly 300 published IRF6 mutations and compared the distribution of these mutations with IRF6 variants obtained from the 1kGP and ESP exomes. We found that mutations causing VWS were significantly over-represented in the DNA-binding domain and for the most part were absent from control exomes, indicating that they are likely to be truly causative for VWS or PPS. These mutations in VWS and PPS only account for 70% of VWS and 97% of PPS. We next hypothesized that mutations in RIPK4, which causes an autosomal recessive pterygia syndrome, could underlie the remaining VWS and/or PPS cases. We found novel homozygous mutations in RIPK4 in two PPS patients. This result has significant clinical ramifications, as counseling of recurrence risk is very different for PPS patients whose disease is caused by dominant IRF6 mutations compared to recessive RIPK4 mutations. Finally, to understand the variable expressivity of VWS and PPS we performed an association study to identify genetic modifiers. We also looked for genotype-phenotype correlations between the type and location of IRF6 mutations. Although we did not find strong evidence that the candidate genes we selected from GWAS of NSCL/P or other clefting syndromes are modifiers of the VWS or PPS phenotypes, several marginal associations suggest that members of the IRF6 gene regulatory network could act as modifiers. Finally, we found evidence of a larger genotype-phenotype correlation by demonstrating that mutation-negative VWS families have a deficiency of cleft lip phenotypes. Together this work has advanced our understanding of the genetic basis of this diverse set of cleft lip and palate disorders, informing both the biology of craniofacial development and the clinical care of patients affected by these disorders.

Objetivo: O estudo avaliou, cefalometricamente, crianças na faixa etária de sete a dez anos, entre as diferentes estratificações da SAOS e o grupo controle, com relação às alterações esqueléticas e faciais e o posicionamento do osso hioide. Casuística e Método: Foram avaliadas 76 crianças, com idades entre sete e dez anos, em fase de dentição mista, sem histórico de tratamento ortodôntico, fonoaudiológico ou cirúrgico otorrinolaringológico. Todas as crianças foram submetidas à avaliação otorrinolaringológica e polissonográfica em laboratório do sono, além da realização do exame cefalométrico. Os participantes foram, também subdivididos em grupos, de acordo com a gravidade da SAOS. Das 76 crianças, 14 constituíram o grupo controle; 62 apresentavam SAOS, sendo 46 classificadas como SAOS leve e 16 SAOS moderada ou grave. Todas as crianças foram submetidas à cefalometria lateral para obtenção de medidas lineares craniofaciais e medidas específicas do osso hioide. Essas medidas foram comparadas entre si dentro dos diferentes grupos pelo teste t de Student (correlação de Welch) e correlacionadas com o valor do Índice de apneias obstrutivas + hiponeias (IAOH) do paciente por meio do teste de correlação de Pearson. O nível de significância estabelecido foi p<0,05. Resultados: Observouse maior distância do osso hioide em relação ao plano mandibular no grupo SAOS, quando comparado ao controle (p=0,03). Entre os dois subgrupos da SAOS, os pacientes com doença moderada ou grave apresentaram significativa menor distância horizontal entre o hioide e a parede posterior da faringe (p=0,03), quando comparados aos com SAOS leve. Na correlação entre as medidas cefalométricas e o IAOH, essas mesmas duas medidas apresentaram relação significativa, sendo a correlação positiva para distância do hioide para o plano mandibular (p=0,04) e negativa para distância horizontal do hioide com a faringe (p=0,006). Para as variáveis cefalométricas faciais, não se observou diferença significativa entre os grupos. Conclusão: A posição do osso hioide, em crianças de sete a dez anos, foi caracterizada pela inferiorização naquelas com a doença e posteriorização em pacientes com maior gravidade da SAOS. Para as medidas craniofaciais lineares não houve diferença estatística
Objective: The study evaluated cephalometric children aged 7-10 years between the different strata of OSA and control groups, with the skeletal and facial changes and the position of the hyoid bone. Casuistic and Method: This study included 76 children, aged between 7 and 10 years in mixed dentition phase, with no history of orthodontic treatment, speech therapy or surgical otorhinolaryngological. All children were submitted to otorhinolaryngological examination and polysomnography in a sleep laboratory, as well as holding the cephalometric examination. The participants were then divided into groups according to the severity of OSA. Of the 76 children of research, 14 constitute the control group; 62 children are affected of OSAS, 46 classified as mild OSA and 16 moderate or severe OSA. All children underwent lateral cephalometric, to obtain craniofacial linear measurements and specific measurements of the hyoid bone. The measurements were compared to each other within the different groups by Student\'s t-test (Welch correlation) and correlated with the OAHI value of the patient through the Pearson correlation test. The level of significance was set at p<0.05. Results: There was a greater distance from the hyoid bone to the mandibular plane in the OSA group when compared to control (p = 0.03). Between the two subgroups of OSAS, patients with moderate or severe impairment had significant lower horizontal distance between the hyoid and the posterior pharyngeal wall (p=0.03) when compared to patients with mild OSA. The correlation between the cephalometric and OAHI measures, these same two measures had a significant relationship with the positive correlation to distance from the hyoid to the mandibular plane (p=0.04) and negative for the horizontal distance from the hyoid to the throat (p=0.006). For facial cephalometric variables, there was no significant difference between groups. Conclusion: The position of the hyoid bone in children 7-10 years was characterized by inferiority in children with the disease and posteriorization in patients with more gravity of OSA. For craniofacial linear measurements showed no statistical difference

Le syndrome de Goldenhar ou OAVS est une maladie du développement impliquant les deux premiers arcs branchiaux. Très hétérogène, elle est caractérisée par des anomalies des oreilles,des yeux et des vertèbres ainsi que par une microsomie hémifaciale. Des causes environnementales (exposition à l’Acide Rétinoïque (AR) durant la grossesse) et des causes génétiques (anomalies chromosomiques) ont été évoquées, mais aucun gène n’était directement associé à ce spectre. L’objectif de ce projet est donc d’identifier des gènes impliqués dans le spectre OAV. Des approches pangénomiques par séquençage nouvelle génération (exome,panels de gènes ciblés) ont été utilisées pour identifier des gènes candidats. L’identification de mutations dans MYT1 et l’inactivation transitoire de son l’homologue myt1a chez le poisson zèbre ont confirmé son rôle dans le développement cranio-facial et son implication dans l’OAVS. La validation fonctionnelle de ces mutations a été réalisée in vitro. Cible de la voie de l’Acide Rétinoïque (AR), MYT1 agit également comme répresseur des Récepteurs de l’AR permettant son rétrocontrôle négatif. Une approche toxicologique (traitements à l’AR de souris gestantes pendant une période clef du développement embryonnaire) a permis l’identification de protéines et de voies de signalisation dérégulées chez les embryons traités. L’étude de ces protéines modulées et notamment de celles déjà impliquées dans le développement cranio-facial tend à renforcer le lien entre AR et OAVS et offre des pistes intéressantes quant à l’identification de nouveaux gènes candidats pour ce syndrome, ces protéines pouvant être codées par des gènes potentiellement mutés chez des patients OAVS
Goldenhar syndrome or Oculo-Auriculo-Vertebral Spectrum (OAVS) is a rare developmental disorder involving the first and the second pharyngeal arches. Extremely heterogeneous, it is characterized by hemifacial microsomia, asymmetric ears, ocular and vertebral abnormalities. Various etiologies have been suggested including environmental factors, especially embryonic Retinoic Acid (RA) exposure during pregnancy, and genetic causes (various chromosomal abnormalities). However, no gene had been formally implicated in this syndrome so far. The goal of this project is to identify genes involved in OAVS. Novel pangenomic approaches by Next generation Sequencing (Whole Exome Sequencing and Target genes Panel) were used to find new candidate genes. Identification of mutations in MYT1 and the transient knockdown experiments in zebrafish confirmed its implication in OAVS. Our in vitro studies provided functional characterization of these mutations and supported the link between MYT1 and RA signaling pathway. Thus, MYT1 is a target of RA but also acts as a repressor of RA Receptors and so, participates at the negative feedback. Toxicological approach was also performed by treatment of gestational mice by all-trans RA during a critical window of embryonic development. It led to a deregulation of proteins and to a modulation of cellular pathways in treated embryos. Studying the proteins whose expression is altered following the treatment, especially the proteins already involved in craniofacial development, could led to the identification of new candidate genes for OAVS and thus, may allow to better decipher the pathogenic mechanisms

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A síndrome da apnéia e hipopnéia obstrutiva do sono (SAHOS) caracteriza-se pela obstrução completa ou parcial das vias aéreas superiores durante o sono sendo comum em indivíduos portadores de Síndrome de Down (SD). O objetivo neste estudo é comparar, por meio da análise em radiografias cefalométricas, em norma lateral, características anatômicas craniofaciais associadas às vias aéreas superiores entre indivíduos portadores de SD, indivíduos portadores de SAHOS e indivíduos não sindrômicos e sem alterações craniofaciais. Além disso, verificar a existência de dimorfismo sexual em relação a essas características nos grupos estudados. Foram realizadas análises computadorizadas em 43 radiografias cefalométricas laterais de indivíduos portadores de SD com idades entre 18 e 34 anos, 26 de indivíduos portadores da SAHOS com idades entre 20 e 70 anos e 29 radiografias cefalométricas de indivíduos não portadores de SD e sem características clínicas de SAHOS com idades entre 18 e 35 anos. Foram avaliadas 14 medidas lineares por meio do software Radiocef Studio 2. Os dados obtidos foram comparados e submetidos à análise de variância (ANOVA) e teste post-hoc de Tukey. Concluimos que existem alterações craniofaciais significantes entre indivíduos portadores de SAHOS e indivíduos não sindrômicos tais como: menor comprimento maxilar e mandibular, naso, oro e hipofaringe com dimensões reduzidas, maior comprimento do palato mole, espaço retropalatal estreitado e osso hióide posicionado mais inferior e anteriormentemente. Dentre as alterações relacionadas à SAHOS, foram encontrados nos indivíduos portadores de SD, menor comprimento da base do crânio, menor comprimento maxilar e mandibular, naso e hipofaringe reduzidas, palato mole aumentado, espaço retropalatal reduzido e osso hióide posicionado mais inferior e anteriormentemente...
Obstructive sleep apnea syndrome is characterized by complete or partial obstruction of the upper airway during sleep, being common in individuals with Down syndrome. The aim of this study is to compare, through analysis of cephalometric radiographs in lateral norm, craniofacial morphology associated with upper airway between individuals with Down syndrome, individuals with obstructive sleep apnea syndrome and non syndromic individuals. Moreover, verify if there is sexual dimorphism in relation to changes in these groups. Computer analysis were performed in 43 lateral cephalometric radiographs of individuals with Down syndrome aged between 18 and 34 years, 26 patients of obstructive sleep apnea syndrome with ages between 20 and 70 years and 29 cephalometric radiographs of non syndromic individuals aged 18 and 35 years old. The analyses were performed using the software Radiocef Studio 2. The data were compared and submitted to analysis of variance (ANOVA) and post-hoc test of Tukey. It was concluded that there are significant craniofacial changes between individuals with and without obstructive sleep apnea syndrome on the lower maxillar and mandibular length, naso, oro and hypopharynx with reduced dimensions, increased length of the soft palate, post-palatal region closer, inferiorly and anteriorly positioned hyoid bone. Among the changes related to obstructive sleep apnea syndrome, that were found in individuals with Down syndrome, the lower length of the base of the skull, lower jaw and mandibular length, reduced nasal and hypo pharynx, longer soft palate, post-palatal region reduced and inferiorly and anteriorly positioned hyoid bone. There is also sexual dimorphism in some factors analyzed: larger anterior skull base, greater length of the maxilla and mandible were found in males in all groups.

Resumo: A síndrome da apnéia e hipopnéia obstrutiva do sono (SAHOS) caracteriza-se pela obstrução completa ou parcial das vias aéreas superiores durante o sono sendo comum em indivíduos portadores de Síndrome de Down (SD). O objetivo neste estudo é comparar, por meio da análise em radiografias cefalométricas, em norma lateral, características anatômicas craniofaciais associadas às vias aéreas superiores entre indivíduos portadores de SD, indivíduos portadores de SAHOS e indivíduos não sindrômicos e sem alterações craniofaciais. Além disso, verificar a existência de dimorfismo sexual em relação a essas características nos grupos estudados. Foram realizadas análises computadorizadas em 43 radiografias cefalométricas laterais de indivíduos portadores de SD com idades entre 18 e 34 anos, 26 de indivíduos portadores da SAHOS com idades entre 20 e 70 anos e 29 radiografias cefalométricas de indivíduos não portadores de SD e sem características clínicas de SAHOS com idades entre 18 e 35 anos. Foram avaliadas 14 medidas lineares por meio do software Radiocef Studio 2. Os dados obtidos foram comparados e submetidos à análise de variância (ANOVA) e teste post-hoc de Tukey. Concluimos que existem alterações craniofaciais significantes entre indivíduos portadores de SAHOS e indivíduos não sindrômicos tais como: menor comprimento maxilar e mandibular, naso, oro e hipofaringe com dimensões reduzidas, maior comprimento do palato mole, espaço retropalatal estreitado e osso hióide posicionado mais inferior e anteriormentemente. Dentre as alterações relacionadas à SAHOS, foram encontrados nos indivíduos portadores de SD, menor comprimento da base do crânio, menor comprimento maxilar e mandibular, naso e hipofaringe reduzidas, palato mole aumentado, espaço retropalatal reduzido e osso hióide posicionado mais inferior e anteriormentemente... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Obstructive sleep apnea syndrome is characterized by complete or partial obstruction of the upper airway during sleep, being common in individuals with Down syndrome. The aim of this study is to compare, through analysis of cephalometric radiographs in lateral norm, craniofacial morphology associated with upper airway between individuals with Down syndrome, individuals with obstructive sleep apnea syndrome and non syndromic individuals. Moreover, verify if there is sexual dimorphism in relation to changes in these groups. Computer analysis were performed in 43 lateral cephalometric radiographs of individuals with Down syndrome aged between 18 and 34 years, 26 patients of obstructive sleep apnea syndrome with ages between 20 and 70 years and 29 cephalometric radiographs of non syndromic individuals aged 18 and 35 years old. The analyses were performed using the software Radiocef Studio 2. The data were compared and submitted to analysis of variance (ANOVA) and post-hoc test of Tukey. It was concluded that there are significant craniofacial changes between individuals with and without obstructive sleep apnea syndrome on the lower maxillar and mandibular length, naso, oro and hypopharynx with reduced dimensions, increased length of the soft palate, post-palatal region closer, inferiorly and anteriorly positioned hyoid bone. Among the changes related to obstructive sleep apnea syndrome, that were found in individuals with Down syndrome, the lower length of the base of the skull, lower jaw and mandibular length, reduced nasal and hypo pharynx, longer soft palate, post-palatal region reduced and inferiorly and anteriorly positioned hyoid bone. There is also sexual dimorphism in some factors analyzed: larger anterior skull base, greater length of the maxilla and mandible were found in males in all groups.
Orientador: Luiz Cesar de Moraes
Coorientador: João Carlos da Rocha
Banca: Jefferson Luis Oshiro Tanaka
Banca: Edmundo Medici Filho
Mestre

INTRODUÇÃO: Pacientes com deficiência de GH e síndrome de Turner, associados a baixa estatura, são beneficiados com o tratamento com GH. Há controvérsias sobre a atuação deletéria do GH no crescimento craniofacial, porém a maioria dos trabalhos é retrospectiva. Nosso objetivo foi realizar estudo prospectivo para avaliar o crescimento craniofacial de pacientes em tratamento com GH e o possível desenvolvimento de traços acromegálicos. CASUÍSTICA: 30 pacientes com idade cronológica de 4,6 a 23 anos e idade óssea de 1,5 a 13 anos divididos em 3 grupos baseados no diagnóstico e uso de GH: grupo 1- pacientes virgem de tratamento com GH portadores de hipopituitarismo e deficiência isolada (n=6); grupo 2: pacientes já em tratamento com GH: portadores de hipopituitarismo e deficiência isolada (n=16); grupo 3: pacientes com síndrome de Turner em tratamento com GH (n=8). A dose do GH utilizada foi de 0.1 a 0.15 U/kg/dia, via subcutânea, à noite, por 2 a 11 anos. MÉTODOS: medidas antropométricas (altura, pés e mãos), radiografia panorâmica, telerradiografia seguida pela análise cefalométrica de Ricketts e medidas lineares da base do crânio, altura facial, terço inferior da face, mandíbula e maxila, e fotografia facial de frente e perfil anualmente, por no mínimo 3 anos. As medidas lineares citadas foram comparadas com a média da população brasileira e entre si para avaliar o desenvolvimento craniofacial individual. As medidas de mãos e pés foram comparadas com atlas de morfometria e consideradas alteradas quando >P97. Os níveis de IGF1 e IGFBP3 foram mensurados a cada 6 meses para adequação da dose de GH. Os resultados foram analisados estatisticamente tomando-se como significantes valores de p<0,05. RESULTADOS: grupos 1 e 2 (deficiência isolada de GH ou hipopituitarismo): 3 pacientes com perfil desarmonioso obtiveram harmonia, 2 pacientes devido ao crescimento mandibular e um paciente devido ao crescimento maxilar, nenhum paciente desenvolveu desarmonia facial; observamos aumento significante da base posterior do crânio, mandíbula e terço inferior da face (p<0,05). Grupo 3 (síndrome de Turner): 2 pacientes com face desarmoniosa obtiveram harmonia, devido ao crescimento mandibular e nenhuma paciente desenvolveu desarmonia facial. Todos os pacientes, quando comparadas a análise cefalométrica de Ricketts inicial e final, mantiveram o mesmo padrão de crescimento facial. Observamos aumento das mãos em 2 pacientes (1 do sexo masculino com deficiência de GH e outra com síndrome de Turner), enquanto que o aumento dos pés foi observado em 50% das pacientes com síndrome de Turner e em 32% dos pacientes com deficiência de GH. CONCLUSÕES: A comparação das medidas cefalométricas do grupo de pacientes com deficiência de GH, virgem de tratamento, demonstrou maior atuação do GH no crescimento da base posterior do crânio e mandíbula; todos os pacientes mantiveram o mesmo padrão de crescimento craniofacial durante o acompanhamento; não houve correlação estatisticamente significante entre as medidas cefalométricas e a harmonia da face, portanto a associação dos métodos de cefalometria e análise facial por fotografia é necessária para avaliar a atuação do GH no crescimento craniofacial, houve melhora da harmonia facial em 28% dos pacientes retrognatas, devido ao crescimento mandibular, portanto pacientes retrognatas podem ser beneficiados com o tratamento com GH; não observamos desenvolvimento de desproporções faciais e nenhum paciente desenvolveu desarmonia facial no decorrer do tratamento com doses padronizadas de GH. Observamos, no entanto, aumento das extremidades, principalmente dos pés.
INTRODUCTION: Patients with GH deficiency and Turner syndrome, associated to short stature can benefit from GH treatment. There are controversies on the deleterious effect of GH on craniofacial growth; however, most of the studies are retrospective. Our objective was to carry out a prospective study to evaluate the craniofacial growth of patients in treatment with GH and the possible development of acromegalic features. PATIENTS: 30 patients with chronological age of 4.6 to 23 years and bone age of 1.5 to 13 years divided in 3 groups based on the diagnosis and GH use: group 1- patients with hypopituitarism and isolated GH deficiency naïve to GH treatment (n=6); group 2: patients with hypopituitarism and isolated GH deficiency (n=16) and group 3: patients with Turner syndrome, both already on GH treatment (n=8). GH treatment (0.1 to 0.15 U/kg/day, subcutaneously) was carried out at the night for 2 to 11 years. METHODS: Anthropometrical (height, hands and feet) measurements, panoramic x-ray, teleradiography followed by cephalometric analysis according to Ricketts and linear measurements of the skull base, facial height, lower third of the face, lower jaw and maxilla, and frontal and profile analysis of face by photography were made annually, for at least 3 years. The mentioned linear measurements were compared with the average Brazilian population and among themselves to evaluate the individual craniofacial development. The hand and foot size measurements were compared with a morphometric atlas and were considered increased when >P97. The levels of IGF1 and IGFBP3 were measured each 6 months for GH dose adequacy. The results were analyzed statistically and p values < 0.05 were considered statistically significant. RESULTS: Group 1 and 2 with isolated GH deficiency or hypopituitarism: 3 patients with disharmonious profile attained harmony, 2 due to the mandibular growth and 1 patient due to maxillary growth; no patient developed facial disharmony; we observed a significant increase of the posterior skull base, inferior jaw and lower third of the face (P<0.05). Group 3 with Turner syndrome: 2 patients with facial disharmony obtained harmony due to the mandibular growth and no patient developed facial disharmony. All of the patients maintained the same pattern of facial growth when the initial and final cephalometric analyses according to Ricketts were compared. Hand size increase was observed in 2 patients (1 with GH deficiency and another with Turner syndrome); foot size increase was observed in 50% of the patients with Turner syndrome and in 32% of the patients with GH deficiency. CONCLUSIONS: The comparison of the cephalometric measurements of the group with GH deficiency naïve to GH treatment, demonstrated a greater GH effect on the growth of the posterior skull base and jaw; all of the patients had kept the same craniofacial growth pattern during the follow-up; there was no statistically significant correlation between the cephalometric measurements and facial harmony; therefore, the association of the methods of cephalometric and facial analysis through photography is mandatory to evaluate the effect of GH on craniofacial growth. There was an improvement in the facial harmony in 28% of the retrognathic patients due to mandibular growth; therefore, patients with mandibular retrognathism can benefit from GH treatment. None of the patients treated with standardized doses of GH developed facial disharmony during treatment. We observed however, an increase of the extremities, mainly of the feet.

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
Introdução: As anomalias congénitas abrangem alterações de estrutura, função e metabolismo da criança. Resultantes de alterações físicas e /ou mentais, podendo estar presentes logo no nascimento ou manifestar-se mais tardiamente. Estima-se que 7,6 milhões de crianças ao nascimento sejam portadoras de uma anomalia congénita. Qualquer alteração no desenvolvimento embrionário pode originar anomalias congénitas que podem variar desde pequenas assimetrias até defeitos com maiores comprometimentos estéticos e funcionais. Objetivo: O objetivo do presente trabalho é dar a conhecer a existência de algumas anomalias congénitas com grande envolvimento da cavidade oral provocando más oclusões devido a erupções dentárias alteradas e alterações no crescimento dos ossos da face. Algumas dessas anomalias são: Fenda Lábio-Palatina, Disostose Cleidocraniana, Disostose Craniofacial entre outras. Materiais e Métodos: Pesquisou-se em duas bases de dados a literatura relevante quanto à temática proposta, com limite temporal dos últimos dez anos e com as seguintes palavras-chaves: anomalias congénitas com manifestações orais, fenda Lábiopalatina, Disostose Cleidocraniana, Disostose Crâniofacial, Disostose Mandíbulo- Facial, Torcicolo, Sífilis Congénita, Toxoplasmose Congénita, Paralisia Cerebral, Síndrome Incontinência Pigmentar, Paralisia Facial, Displasia Ectodérmica, Síndrome de Rieger, Síndrome de Pierre-Robin, Síndrome de Hallerman-Streiff. Os artigos foram selecionados segundo o seu rigor científico e interesse para o tema. Conclusões: A etiologia das anomalias congénitas é multifatorial sendo idêntica em quase todas as anomalias. As anomalias craniofaciais têm um número significativo dentro das anomalias congénitas sendo por isso muito diversificadas e complexas. A fenda Lábio-palatina é das anomalias craniofaciais mais frequente e conclui-se que as manifestações orais são idênticas em cada anomalia congénita estudada. Introduction: Congenital anomalies include changes in structure, function and metabolism of the child. Resulting from physical and / or mental abnormalities that can be presented at birth or may manifest themselves later. It is estimated that 7.6 million children are born with a congenital anomaly. Any change in embryonic development can cause birth defects which may vary from small asymmetries to defects with higher aesthetic and functional impairment. Objective: This work intends to shed some light on the existence of some congenital anomalies with great involvement on the oral cavity causing malocclusion due to altered dental eruptions and changes in facial bones' growth. Some of these anomalies are: Cleft Lip and Palate, cleidocranial dysostosis, Craniofacial dysostosis among others. Materials and Methods: Two databases on relevant literature regarding the proposed theme were searched. The search time span was comprised in the last ten years and keywords like congenital anomalies with oral manifestations, cleft lip and palate, cleidocranial dysostosis, craniofacial dysostosis, mandibular-facial dysostosis, Torticollis, Congenital Syphilis, Congenital Toxoplasmosis, Cerebral Palsy, Incontinence Pigmentosa Syndrome, Facial Paralysis, Ectodermal Dysplasia, Rieger Syndrome, Pierre -Robin syndrome, Hallerman-Streiff were used. Articles were selected according to their scientific rigor and relevance to the theme. Conclusions: The etiology of congenital abnormalities is multifactorial, being identical in almost all anomalies. Craniofacial anomalies are predominant within congenital anomalies, being diverse and complex. The cleft lip and palate are the most common craniofacial anomalies. Thus, it was concluded that oral manifestations are identical in each study congenital anomaly.

This thesis further delineates the molecular genetic basis of a relatively common craniofacial condition, coronal craniosynostosis. It used whole-exome sequencing to identify novel disease genes in patients with non-syndromic coronal synostosis and negative genetic testing. Initially, 2 patients were identified with damaging, frameshift mutations in a gene not previously linked with craniosynostosis – Transcription Factor 12 (TCF12). A further intronic mutation was identified in a third patient. This gene encodes a transcription factor that dimerises with TWIST1, mutations of which cause Saethre-Chotzen syndrome, also associated with coronal synostosis. Screening 344 undiagnosed patients identified 35 further mutations, all with coronal synostosis with 14 cases arising de novo. This work was published and testing for TCF12-related craniosynostosis was translated clinically. Significant non-penetrance (60%) was identified in mutation-positive relatives and the genetic background was investigated. Firstly, analysis of parental origins of de novo mutations identified 6 of paternal origin and helped refine haplotype assignment. Secondly, haplotype analysis of TCF12-mutation carriers revealed modest correlation with phenotypic status, but this was insufficient to be useful in clinical testing. Thirdly, TCF12 haplotypes were analysed for association with non-syndromic coronal synostosis, but no significant association was found. Further exome sequencing revealed a de novo frameshift mutation in Transcription Factor 20 (TCF20) in a patient with coronal synostosis and autism, although the mutation only correlated with the latter phenotype. Analysis of 5 trios revealed a novel variant in myosin heavy chain 4 (MYH4) in 1 family, although its role in suture development is uncertain. Reviewing pooled exome data from 19 mutation-negative patients revealed no further disease genes. In summary, this thesis describes novel gene discovery, defines a new clinical entity and investigates genetic background of penetrant and non-penetrant individuals. Further exome sequencing identified another disease gene, a de novo mutation and compiled lists of damaging variants to allow future work.

Background Mandibular distraction osteogenesis (MDO) is becoming increasingly commonly used as the primary surgical option for neonates and infants with upper airway obstruction secondary to micrognathia or to facilitate decannulation for tracheostomy dependent children. Objectives The objective of this review was to identify and synthesize the best available evidence on the effectiveness of MDO on airway patency, feeding, gastro-esophageal reflux (GORD) and long-term development in children born with upper airway obstruction secondary to micrognathia. This review also aims to determine the ideal rate of distraction, and compare outcomes of external and internal distractors in this patient group. Inclusion criteria The inclusion criterion included studies in children with clinical evidence of micrognathia/Pierre Robin Sequence (PRS) who have failed conservative treatments, including both syndromic (sMicro) and non-syndromic isolated PRS (iPRS) patients. The intervention is patients who have undergone bilateral distraction osteogenesis to prevent a tracheostomy or to facilitate decannulation. The comparator intervention is patients who underwent a tracheostomy alone. The outcomes of interest include relief of airway obstruction with MDO, decannulation of tracheostomy dependent patients, feeding and reflux changes, surgical outcomes such as comparison of rate of distraction and type of distractor. All study designs were included. Methods The databases searched included PubMed, Embase, Scopus, Web of Knowledge and grey literature sources. Of the 4815 studies found in the initial search, only 66 were included after critical appraisal. Due to the nature of the studies included, a meta-analysis was not possible. The data was pooled by calculating weighted means. Results Primary MDO for the relief of upper airway obstruction was successful in 95% of cases in the literature. Syndromic (sMicro) patients had odds of failure that were four times higher than those of iPRS patients. The most common causes of failure are previously undiagnosed lower airway obstruction, central apnoea, undiagnosed neurological abnormalities and complex multiorgan anomalies. Mandibular distraction osteogenesis (MDO) was less effective (80.3% success rate) at facilitating decannulation of tracheostomy dependent children. Failure in these patients was most commonly due to severe preoperative gastro-oesophageal reflux disease (GORD), swallowing dysfunction and tracheostomy related complications. The failure rate was higher when MDO was performed at an age of ≥24 months for this group of patients. Approximately 84% of children can be exclusively oral fed after MDO. The odds of needing feeding adjuncts were five times higher in syndromic children. There was a trend towards a growth decline in the first six weeks after surgery. MDO relieves GORD in the majority of patients. Patients who were tracheostomy dependent with severe GORD were at higher risk of failure to decannulate after MDO. There was no difference in success rate when comparing a distraction rate of 1mm/day with 2mm/day. External distractors were associated with a higher rate of failure and complications compared to internal distractors. Overall, there was a paucity of long-term results in the literature. Recurrence of airway distress may occur due to a relapse of retrognathia or TMJ ankylosis. Conclusion Mandibular distraction osteogenesis is an effective technique for preventing tracheostomy in children with airway obstruction secondary to micrognathia (Level 4 evidence). Thorough airway evaluation and sleep study pre-MDO is necessary to exclude multilevel airway obstruction and central apnoea. Mandibular distraction osteogenesis has a slightly lower success rate at facilitating decannulation. Thorough airway evaluation, assessment for reflux and swallowing dysfunction are necessary prior to surgery. Mandibular distraction osteogenesis is effective at alleviating feeding problems and reflux symptoms in these children. Care needs to be taken to avoid a general growth decline that has been reported in the first six weeks after surgery. Distracting at a rate of 1mm/day or 2mm/day below the age of 12 months is safe. Internal distractors have a higher success rate and a lower rate of complications than external distractors. More studies are needed to evaluate the long-term implications of MDO on facial development and long-term complications.
Thesis (M.Clin.Sc.) -- University of Adelaide, School of Translational Health Science, 2015

Indiana University-Purdue University Indianapolis (IUPUI)
Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and occurs in ~1 of every 700 live births. Individuals with DS present craniofacial abnormalities, specifically an undersized, dysmorphic mandible which may lead to difficulty with eating, breathing, and speech. Using the Ts65Dn DS mouse model, which mirrors these phenotypes and contains three copies of ~50% Hsa21 homologues, our lab has traced the mandibular deficit to a neural crest cell (NCC) deficiency in the first pharyngeal arch (PA1 or mandibular precursor) at embryonic day 9.5 (E9.5). At E9.5, the PA1 is reduced in size and contains fewer cells due to fewer NCC populating the PA1 from the neural tube (NT) as well as reduced cellular proliferation in the PA1. We hypothesize that both the deficits in NCC migration and proliferation may cause the reduction in size of the PA1. To identify potential genetic mechanisms responsible for trisomic PA1 deficits, we generated RNA-sequence (RNA-seq) data from euploid and trisomic E9.25 NT and E9.5 PA1 (time points occurring before and after observed deficits) using a next-generation sequencing platform. Analysis of RNA-seq data revealed differential trisomic expression of 53 genes from E9.25 NT and 364 genes from E9.5 PA1, five of which are present in three copies in Ts65Dn. We also further analyzed the data to find that fewer alternative splicing events occur in trisomic tissues compared to euploid tissues and in PA1 tissue compared to NT tissue. In a subsequent study, to test gene-specific treatments to rescue PA1 deficits, we targeted Dyrk1A, an overexpressed DS candidate gene implicated in many DS phenotypes and predicted to cause the NCC and PA1 deficiencies. We hypothesize that treatment of pregnant Ts65Dn mothers with Epigallocatechin gallate (EGCG), a known Dyrk1A inhibitor, will correct NCC deficits and rescue the undersized PA1 in trisomic E9.5 embryos. To test our hypothesis, we treated pregnant Ts65Dn mothers with EGCG from either gestational day 7 (G7) to G8 or G0 to G9.5. Our study found an increase in PA1 volume and NCC number in trisomic E9.5 embryos after treatment on G7 and G8, but observed no significant improvements in NCC deficits following G0-G9.5 treatment. We also observed a developmental delay of embryos from trisomic mothers treated with EGCG from G0-G9.5. Together, these data show that timing and sufficient dosage of EGCG treatment is most effective during the developmental window the few days before NCC deficits arise, during G7 and G8, and may be ineffective or harmful when administered at earlier developmental time points. Together, the findings of both studies offer a better understanding of potential mechanisms altered by trisomy as well as preclinical evidence for EGCG as a potential prenatal therapy for craniofacial disorders linked to DS.

碩士
長庚大學
顱顏口腔醫學研究所
98
Purpose: The purpose of the study is to investigate the treatment effect and stability of patients with syndromic craniosynostosis (SCS). Design: Serial case study. Setting: Consecutive patients with SCS who were treated by DO in Chang Gung Craniofacial Center, Taipei, Taiwan from 1988 to 2003. Patients and intervention: A total of 8 patients of SCS with average age of 9.2 year at the time of surgery were included. Five patients recieved Monobloc DO and three received Le Fort III DO. Methods of Measurements: Clinical charts were reviewed, serial cephalometric radiographs were superimposed and measured to evaluate the treatment and post-treatment changes. The three-dimensional computerized tomographs (3D CT) were used to observe the alteration of intracranial volumn, orbital protrusion and upper airway space. The mean follow up period was 2 years. Results: The midface complex moved forward by 15 mm in average with counterclockwise rotation . The midface had no further sagittal forward growth after DO. The supraorbital region showed forward expansion in cases with Monobloc DO. The 3D CT revealed an increase of intracranial and upper airway volume, and decrease of eye globe protrusion. Conclusion: DO is an effective treatment for patients with SCS. The midface demonstrated mild vertical growth but no sagittal growth after DO. The frontal bone remodeling continued after Monobloc DO. The potential of solving vital problems, such as increase ICP, proptosis and airway obstruction was achieved.

Indiana University-Purdue University Indianapolis (IUPUI)
Trisomy 21 occurs in approximately 1 out of 750 live births and causes brachycephaly, a small oral cavity, a shortened mid-face, and mental impairments in individuals with Down syndrome (DS). Craniofacial dysmorphology occurs in essentially all individuals with trisomy 21 and causes functional difficulties. Mouse models are commonly used to study the etiology of human disorders because of the conserved phenotypes between species. The Ts65Dn Down syndrome mouse model has triplicated homologues for approximately half the genes on human chromosome 21 and exhibits many phenotypes that parallel those found in individuals with DS. Specifically, newborn and adult Ts65Dn mice display similar craniofacial defects as humans with DS. Ts65Dn embryos also exhibit smaller mandibular precursors than their euploid littermates at embryonic day 9.5 (E9.5). Furthermore, Ts65Dn mice exhibit reduced birth weight which suggests a possible generalized delay in overall embryonic growth. Based on previous research at E9.5, it was hypothesized that Ts65Dn E13.5 embryos would have reduced mandibular precursors with altered gene expression. It was also hypothesized that other neural crest derived structures would be reduced in trisomic embryos. Using morphological measurements it was determined that the mandible, Meckel’s cartilage, and hyoid cartilage were significantly reduced in E13.5 trisomic embryos. The tongue was of similar size in trisomic and euploid embryos while cardiac and brain tissue volumes were not significantly different between genotypes. Analysis of total embryonic size at E9.5 and E13.5 revealed smaller trisomic embryos with developmental attenuation that was not related to maternal trisomy. A microarray analysis performed on the mandibular precursor revealed 155 differentially expressed non-trisomic genes. Sox9 was of particular interest for its role in cartilage condensation and endochondral ossification. It was hypothesized that the overexpression of Sox9 in the developing mandible would be localized to Meckel’s and hyoid cartilages. Immunohistochemistry performed on the mandibular precursor confirmed an overexpression of Sox9 in both Meckel’s and the hyoid cartilages. This research provides further insight into the development of trisomic tissues, both neural crest and non-neural crest-derived, and also the specific molecular mechanisms that negatively affect mandibular development in Ts65Dn mice and presumably individuals with Down syndrome.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
A síndrome de apneia obstrutiva do sono (SAOS) é definida pela obstrução das vias aéreas superiores, com repercussões na ventilação pulmonar durante o sono. Com uma prevalência de até 5% na população pediátrica, esta implica a sobreutilização dos cuidados de saúde e constitui uma causa de morbilidade na infância. Neste grupo etário, a etiologia mais frequente é a hipertrofia das tonsilas palatinas e/ou faríngeas. A sintomatologia é pouco específica, sendo a roncopatia a manifestação mais frequente. No entanto, tem impacto na qualidade de vida da criança, com possíveis consequências futuras. Existe evidência de causalidade entre a SAOS e determinadas alterações craniofaciais, mas este tópico ainda é alvo de controvérsia. O desenvolvimento craniofacial é um fenómeno complexo, provavelmente influenciado por fatores genéticos e adquiridos. O objetivo desta revisão sistemática é avaliar a existência de anomalias do desenvolvimento craniofacial em crianças diagnosticadas com SAOS, comparando-as com crianças sem SAOS. O estudo deste tema permitirá uma melhor prestação de cuidados, com tratamento mais precoce e melhor prognóstico. A pesquisa bibliográfica recorreu às bases de dados eletrónicas PubMed e EMBASE. Os critérios de inclusão foram: (1) artigos publicados entre 2010 e a data da pesquisa bibliográfica; (2) estudos randomizados e controlados, estudos de caso-controlo, estudos de coorte e revisões sistemáticas; (3) participantes em idade pediátrica; (4) estudo da correlação da SAOS com o desenvolvimento craniofacial; (5) SAOS diagnosticada por anamnese, questionários, exame físico e/ou polissonografia (PSG); (6) avaliação craniofacial clínica ou por cefalometria.A colheita de dados abrangeu: (1) características sociodemográficas da população em estudo (idade, sexo e raça); (2) características clínicas (diagnóstico, sintomatologia, escalas de avaliação e exame físico); (3) dados da PSG; (4) dados cefalométricos. A presente revisão incluiu 9 artigos. A intervenção foi o diagnóstico de SAOS, realizado por métodos válidos, em todos os artigos. Para a análise craniofacial, todos os autores recorreram a radiografia cefalométrica, associando ou não um exame clínico. A análise incluiu 13 variáveis, divididas pelos planos ântero-posterior/sagital, vertical e transversal. Os resultados foram alvo de uma interpretação sistematizada e qualitativa. As alterações na estrutura craniofacial em crianças com SAOS foram mais acentuadas a nível do retrognatismo mandibular, padrão de crescimento vertical, arcadas mandibulares estreitas e presença de mordida cruzada. As alterações sagitais da base do crânio foram as menos significativas. Nas limitações, destaca-se a heterogeneidade entre estudos e alguns potenciais fatores confundidores, tais como a idade, sexo, raça e gravidade da patologia. Apesar das limitações e falta de evidência estatística em alguns casos, verificamos certas tendências no desenvolvimento, com possível impacto na qualidade de vida destes doentes, a nível clínico. Em conclusão, não obtivemos uma relação causal entre a SAOS e as alterações craniofaciais. No entanto, a avaliação craniofacial poderá ser um instrumento adjuvante no diagnóstico. De facto, se um doente apresentar alterações faciais típicas, tais como maloclusão de classe II, fácies alongada e arcadas mandibulares estreitas, deve levantar a suspeita de SAOS e ser referenciado a consulta de Otorrinolaringologia (ORL), para investigação precoce.
Obstructive sleep apnea syndrome (OSAS) is defined by obstruction of the upper airways, with repercussions on pulmonary ventilation during sleep. With a prevalence up to 5% of the paediatric population, it is a common cause of childhood morbidity, and it implicates an overuse of health-related care. In children, the main etiology of OSAS is tonsil and adenoid hypertrophy. The symptoms are nonspecific, and snoring is the most frequent manifestation. However, this disease has an impact on the patients’ quality of life, with future consequences.Evidence suggests that a causal relationship exists, between OSAS and certain craniofacial anomalies. However, this topic remains controversial. Craniofacial development is a complex process. It is probably influenced by both genetic and acquired factors. This systematic review aims to evaluate the presence of craniofacial development anomalies in children diagnosed with OSAS, comparatively to children without OSAS. The study of this topic will improve patient care, with early treatment and better prognosis.Our bibliographic research included PubMed and EMBASE electronic databases. The inclusion criteria were: (1) publications between 2010 and the date of bibliographic research; (2) randomized controlled trials, case-control studies, cohort studies and systematic reviews; (3) participants in paediatric age; (4) study of the correlation between OSAS and craniofacial development; (5) OSAS diagnosed by medical history, questionnaires, physical exam and/or polissonography (PSG); (6) clinical or cephalometric craniofacial evaluation.The data collection included: (1) sociodemographic features of study population (age, sex and race); (2) clinical features (diagnosis, symptoms, evaluation scales and physical examination); (3) PSG data; (4) cephalometric data. This review included 9 articles. The intervention was the diagnosis of OSAS, which was done by valid methods in all articles. The craniofacial evaluation was done with cephalometric radiography and some studies also included a clinical assessment. The results comprised 13 variables, which were divided by three planes: sagittal, vertical and lateral.We performed a systematic and qualitative interpretation of the results. The main differences were found regarding mandibular retrognatia, vertical growth pattern, narrow jaws and crossbite. The sagittal cranial base measures revealed the least differences between groups.Our study revealed some limitations. We highlight the heterogeneity between studies and some cofounding factors, namely the participants’ age, sex, race and disease severity. Despite the limitations and lack of statistic evidence of some results, we found a tendency to a certain growth pattern. This pattern may have clinical impact on the patients’ quality of life. In conclusion, we did not find a causal relationship between OSAS and craniofacial development. However, the craniofacial evaluation can be useful as an adjuvant tool on the diagnosis of OSAS. In fact, if a patient presents typical facial features (class II maloclusion, long face and narrow jaws) it should be a red flag for OSAS. Therefore, this patient should be referred to an Otolaryngologist (ENT) consult for early evaluation.

"July 2005"
Bibliography: leaves 113-122.
[12], 122 leaves : ill. (some col.), plates (some col.) ; 30 cm.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Thesis (Ph.D.)--University of Adelaide, Dental School and School of Molecular and Biomedical Science, Discipline of Physiology, 2005

"July 2005"
Bibliography: leaves 113-122.
[12], 122 leaves : ill. (some col.), plates (some col.) ; 30 cm.
Thesis (Ph.D.)--University of Adelaide, Dental School and School of Molecular and Biomedical Science, Discipline of Physiology, 2005

Este trabalho tem como objetivo enfatizar as manifestações bucais das síndromes de Apert e Crouzon e apontar informações importantes para o plano de tratamento destes doentes. Foi realizada uma busca nas bases de dados PubMed, Scielo e BVS-Bireme, com o intuito de revisar a literatura científica a cerca do tema. Das craniossinostoses sindrômicas, as mais frequentes são a Síndrome de Apert e a Síndrome de Crouzon, ambas acontecem devido a mutações no gene que codifica o recetor do Fator de Crescimento de Fibroblastos, isto resulta num fechamento precoce das suturas cranianas, podendo por sua vez ocasionar uma hipertensão intracraniana. O tratamento destes pacientes, deve ser realizado em ordem inter e multidisciplinar, e o diagnóstico precoce é de extrema importância para melhorar a qualidade de vida dos portadores e dos seus familiares.
This work aims to emphasize the oral manifestations of the Apert and Crouzon syndromes and to point out important information for the treatment of these patients. A search was made in the databases PubMed, Scielo and BVS-Bireme, with the intention of reviewing the scientific literature on the subject. Among the syndromic craniosynostoses, the most frequent are Apert Syndrome and Crouzon Syndrome, both occur due to mutations in the gene encoding the Fibroblast Growth Factor receptor, this results in an early closure of the cranial sutures, which can cause an intracranial hypertension. The treatment of these patients must be performed in an inter and multidisciplinary order, and early diagnosis is extremely important to improve the quality of life of these patients and their families.