RESUMO
OBJECTIVE: Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo-Auriculo-Dento-Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10+/- ) mutation at skeletal maturity. METHODS: Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10+/- mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro-computed tomography. Landmark-based linear dimensions were measured for the cranial vault, maxilla, mandible, and first molar teeth. Multivariate analysis of variance was performed to assess whether there were significant differences in the craniofacial and dental structures between genotypes and sexes. RESULTS: The craniomaxillary skeleton and the first molar teeth were smaller in the FGF10+/- mice (P < .05), but the mandible was unaffected. Sex did not have a significant effect on these structures (P > .05). Cranial sutural defects were noted in 5/22 (22.7%) mutant versus 2/18 (11.1%) wildtype mice, and cleft palate in only one (4.5%) mutant mouse. None of the mice displayed craniosynostosis, expansive bony lesions, bifid condyles, or impacted teeth. CONCLUSION: The FGF10+/- mutation was associated with craniomaxillary skeletal hypoplasia that probably arose from deficient (delayed) intramembranous ossification of the sutured bones. Overall, the skeletal and dental data suggest that the FGF10 gene plays an important role in the aetiology of craniofacial dysmorphology and malocclusion.
Assuntos
Fissura Palatina , Anormalidades Craniofaciais , Craniossinostoses , Camundongos , Masculino , Feminino , Animais , Fissura Palatina/genética , Microtomografia por Raio-X , Fator 10 de Crescimento de Fibroblastos/genética , Modelos Animais de Doenças , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/genética , Craniossinostoses/genética , Mutação/genéticaRESUMO
OBJECTIVE: Children and adolescents with orofacial clefts may experience ongoing psychosocial impacts due to the continuous nature of cleft treatments, facial and dental differences, and speech and hearing difficulties. The aim of this qualitative systematic review was to better understand the experiences of children and adolescents with orofacial clefts. DESIGN: A systematic search strategy using PubMed, Embase, Emcare, Scopus, and Web of Science databases was performed to identify relevant qualitative studies evaluating the lived experience of children and adolescents with orofacial clefts from inception through to June 2021. Eligible studies were critically appraised using the Joanna Briggs methodology and a meta-aggregative approach. RESULTS: The search identified 2466 studies, with 13 found to meet the inclusion criteria. Extraction of 155 findings resulted in 27 categories, which were meta-aggregated into 7 overarching synthesized findings. These 7 core findings included aspects of child experience and findings that enhanced or impeded child experience at the individual, family, and community levels. CONCLUSIONS: Factors that impeded child experience at the individual, family, and community levels were more pronounced than factors that enhanced their experience among children and adolescents with orofacial clefts. Further initiatives are needed to provide support to individuals, families, and school communities to enhance children's experience of orofacial cleft during the formative childhood and adolescent years.
Assuntos
Fenda Labial , Fissura Palatina , Criança , Adolescente , Humanos , Fenda Labial/psicologia , Fissura Palatina/psicologia , Face , Pesquisa QualitativaRESUMO
ABSTRACT: Metopic craniosynostosis is a condition in which the metopic suture is prematurely fused. Trigonocephaly and hypotelorism are the major abnormal findings associated with synostosis. Fronto-orbital advancement with cranial remodelling procedure is the widely practised method for correction of the deformities. Previously, a few studies have shown a low incidence of secondary raised intracranial pressure after the primary surgery. Thus, we reviewed our database to investigate the outcomes of metopic craniosynostosis treatment between 1999 and 2020 in Cleft and Craniofacial South Australia. One hundred twelve patients (77 males and 35 females) with metopic synostosis were operated. The mean age of primary surgery was 11.1âmonths (range 2.8-131.7âmonths). Ten patients (9%) who had secondary raised intracranial pressure underwent secondary surgery. Among those, the mean age of primary and secondary surgery were 5.4 and 57.1âmonths, respectively. Syndromic patients were significantly revealed to have a higher incidence of secondary raised intracranial pressure. There were three patients (2.7%) who had other secondary procedures (hardware removal and aesthetic contouring procedures). This cohort identified a higher incidence of secondary raised intracranial pressure requiring secondary surgery than previous studies. Syndromic patients were significantly related to secondary raised intracranial pressure. The patients who had raised intracranial pressure tended to have primary correction at younger age. Long-term multidisciplinary follow-up is mandatory. The demand for secondary surgery for metalwork complications or cosmetic contouring is uncommon.
Assuntos
Craniossinostoses , Hipertensão Intracraniana , Procedimentos de Cirurgia Plástica , Criança , Pré-Escolar , Craniossinostoses/cirurgia , Estética Dentária , Feminino , Humanos , Lactente , Hipertensão Intracraniana/cirurgia , Masculino , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Atenção Terciária à SaúdeRESUMO
INTRODUCTION: The mandible is one of the most common facial bones to be injured with great clinical variability across countries caused by assaults, road traffic accidents, and falls. METHODS: A retrospective review was conducted for adult mandibular fractures from January 2012 to January 2017 at the Royal Adelaide Hospital, Adelaide. Our aim was to describe epidemiological trends of mandibular fractures, differences for sex and age, and clinical outcomes. RESULTS: Five hundred sixty five adult patients presented with a mandibular fracture with a male predominance (4.5:1). The mean age was 34.2âyears with men 11.9âyears younger than females (32.0 versus 44.1âyears, P â < â0.001). Assaults represented 58.2% of cases. A quarter of the cohort reported alcohol use. Assaults commonly resulted in angle and symphyseal fractures, whereas almost all falls and road traffic accident resulted in condylar or coronoid fractures. Young men were 1.9 times more likely to have mandibular fractures compared to women, whereas elderly men were 11.8% less likely ( P â<â0.001). The most common fracture was the angle (33.6%) and the angle/symphyseal (14.2%). Men were 2.5 times more likely to have surgery. The complication rate was 10.8% and the re-operative rate was 5.0%. Women had a significantly longer admission of 1.6âdays compared to men (4.4 versus 2.8âdays, P â=â0.003). CONCLUSIONS: Young men are more likely to have mandibular fractures from assaults and have surgery. Young women and elderly females are more likely to have animal and fall-related injuries resulting including in condylar fractures with associated injuries and extended length of stay.
Assuntos
Fraturas Mandibulares , Acidentes de Trânsito , Ossos Faciais/lesões , Feminino , Humanos , Masculino , Fraturas Mandibulares/epidemiologia , Fraturas Mandibulares/cirurgia , Estudos Retrospectivos , Austrália do Sul/epidemiologiaRESUMO
BACKGROUND: The highly conserved Grainyhead-like (Grhl) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead-like 2 (Grhl2) leads to mid-gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning. RESULTS: Here, using four separate Cre-lox conditional deletion models, as well as one genetic epistasis approach (Grhl2+/- ;Edn1+/- double heterozygous mice) we have investigated tissue-specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the ShhCre driver) leads to low-penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx (NestinCre ) leads to small, albeit significant, differences in the proximal-distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm (Sox17-2aiCre ) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm-derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest (Wnt1Cre ) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1. CONCLUSION: Taken together, our study identifies a pharyngeal-epithelium intrinsic, non-cell-autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm-specific role for Grhl2 in the formation and establishment of the mammalian lung.
Assuntos
Epistasia Genética , Regulação da Expressão Gênica no Desenvolvimento , Crânio/embriologia , Fatores de Transcrição/genética , Animais , Camundongos , Crista Neural/metabolismo , Tubo Neural/metabolismo , Crânio/metabolismo , Fatores de Transcrição/metabolismoRESUMO
The highly-conserved Grainyhead-like (Grhl) transcription factors are critical regulators of embryogenesis that regulate cellular survival, proliferation, migration and epithelial integrity, especially during the formation of the craniofacial skeleton. Family member Grhl2 is expressed throughout epithelial tissues during development, and loss of Grhl2 function leads to significant defects in neurulation, abdominal wall closure, formation of the face and fusion of the maxilla/palate. Whereas numerous downstream target genes of Grhl2 have been identified, very little is known about how this crucial developmental transcription factor itself is regulated. Here, using in silico and in utero expression analyses and functional deletion in mice, we have identified a novel 2.4 âkb enhancer element (mm1286) that drives reporter gene expression in a pattern that strongly recapitulates endogenous Grhl2 in the craniofacial primordia, modulates Grhl2 expression in these tissues, and augments Grhl2-mediated closure of the secondary palate. Deletion of this genomic element, in the context of inactivation of one allele of Grhl2 (through generation of double heterozygous Grhl2+/-;mm1286+/- mice), results in a significant predisposition to palatal clefting at birth. Moreover, we found that a highly conserved 325 bp region of mm1286 is both necessary and sufficient for mediating the craniofacial-specific enhancer activity of this region, and that an extremely well-conserved 12-bp sequence within this element (CTGTCAAACAGGT) substantially determines full enhancer function. Together, these data provide valuable new insights into the upstream genomic regulatory landscape responsible for transcriptional control of Grhl2 during palatal closure.
Assuntos
Elementos Facilitadores Genéticos/genética , Loci Gênicos , Neurulação/genética , Palato/embriologia , Fatores de Transcrição/genética , Alelos , Animais , Feminino , Deleção de Genes , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tubo Neural/embriologia , Defeitos do Tubo Neural/genética , Fatores de Transcrição/metabolismoRESUMO
INTRODUCTION: Facial fractures of children are relatively infrequent compared to adults. There are variations in facial fractures depending on the socioeconomic, cultural, and educational factors of the country and time. Our aim is to describe epidemiological trends of facial fractures in the pediatric population, understand differences amongst the age groups, and the impact this has on clinical outcomes and management in South Australia. METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Women and Children's Hosptial, Adelaide. All facial fractures of children, aged 16âyears and below, that attended or were referred to the unit were included in this study. RESULTS: A total of 265 pediatric patients presented with a facial fracture with a male predominance. Some 49.1% occurred from a sports-related injury with bicycle motocross as the single most common type of sport. The mandible was the common fracture type with 21.9% of the total cohort having an associated injury. There were significant differences between boys and girls for age, age groups, mechanism of injury, and type of sport (Pâ<â0.05). Boys were 2.3 times more likely to have a sport-related facial fracture than girls. Early adolescence were 5.2 times more likely to have an orbitozygomatic fracture than children of early childhood (Pâ<â0.05). Age, associated injuries, and sport-related facial fractures were independently associated with increased length of stay (Pâ<â0.001). CONCLUSIONS: There are differences amongst boys and girls and an understanding of these differences can aid the diagnosis and management in a growing child's face.
Assuntos
Traumatismos em Atletas , Traumatismos Faciais , Fraturas Cranianas , Adolescente , Adulto , Traumatismos em Atletas/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Ossos Faciais/lesões , Traumatismos Faciais/epidemiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fraturas Cranianas/epidemiologia , Austrália do Sul/epidemiologiaRESUMO
Cleidocranial dysplasia (CCD) is a rare autosomal dominant disorder caused by mutations in the Runx2 gene. The CCD is characterized by frontal bossing, a patent anterior fontanelle, presence of Wormian bones, midface hypoplasia, multiple dental abnormalities, clavicular hypoplasia or aplasia, skeletal abnormalities, and short stature. The aims of this study are to report the phenotypic manifestations of all patients who presented with CCD and to review the multidisciplinary management of these patients. The longitudinal data of patients with a diagnosis of CCD treated at The Australian Craniofacial Unit from 1980 to 2019 were reviewed. Fourteen patients were identified for inclusion in this study. The age at referral to the unit ranged from 1 week old to 49 years old (mean 11.2 years old). All patients had clinical features of frontal bossing, a patent anterior fontanelle, multiple Wormian bones, midface hypoplasia, abnormal dentition, clavicular hypoplasia/aplasia, and normal intellect. Eleven patients had obstructive sleep apnea. Eight patients had positive family history. Speech issues were found in 6 patients and abnormal hearing was found in 4 patients. Seven patients who underwent skeletal survey were found to have skeletal abnormalities. All patients were evaluated and managed by the multidisciplinary team, which consisted of craniofacial surgeons, pediatric dentists, orthodontists, ENT surgeons, pediatricians, clinical geneticists, radiologists, orthopedic surgeons, and social workers. All patients were treated by dentists/orthodontists requiring multiple surgical interventions and orthodontic treatment. Seven patients who had recurrent ear infection underwent ventilation tube insertion. Seven of 11 patients who had obstructive sleep apnea underwent adenotonsillectomy. Four patients underwent orthognathic surgery to correct midface hypoplasia and malocclusion. Two patients had cranioplasty for correction of metopic depressions. The characteristic findings of patients with CCD involving multiple regions of the body should draw clinicians' attention to the need for multidisciplinary management of these patients.
Assuntos
Displasia Cleidocraniana/diagnóstico , Crânio , Adenoidectomia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Apneia Obstrutiva do Sono , Tonsilectomia , Adulto JovemRESUMO
Advances in molecular biology and nanomedicine based therapies hold promise to obviate the need of multiple surgical interventions (associated with current management) in craniosynostosis by preventing bone re-ossification. One such adjunctive therapy involves application of glypicans 1 and 3 (GPC1 and GPC3) that are BMP inhibitors implicated in downregulating the BMP2 activity in prematurely fusing sutures. Electrochemically anodized Titania nanotube (TNT) arrays have been recognized as a promising localized, long-term drug delivery platform for bone-related therapies. This study presents the application of nanoengineered TNT/Ti implants loaded with recombinant glypicans for craniosynostosis therapy. By using Dual luciferase Reporter assay, we tested the biofunctionality of eluted glypicans from the TNT/Ti implants for BMP2 bioactivity regulation in C2C12 murine myoblast cell line. BMP2 activity was inhibited significantly for up to 15days by the glypicans released from polymer-coated TNT/Ti implants, indicating their potential application in adjunctive craniosynostosis treatment.
Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Craniossinostoses/tratamento farmacológico , Liberação Controlada de Fármacos , Glipicanas/administração & dosagem , Mioblastos/efeitos dos fármacos , Próteses e Implantes , Titânio/química , Animais , Células Cultivadas , Craniossinostoses/metabolismo , Craniossinostoses/patologia , Sistemas de Liberação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Glipicanas/química , Camundongos , Mioblastos/citologia , Mioblastos/metabolismo , Polímeros/químicaRESUMO
INTRODUCTION: Nager syndrome is a rare condition characterized by craniofacial and upper limb abnormalities. It is commonly mistaken for Treacher Collins syndrome, with which it shares the same craniofacial phenotype. However, patients with Treacher Collins do not exhibit hand anomalies, which are seen in patients with Nager syndrome. This paper reviews the multidisciplinary management of patients with Nager syndrome who were treated at the Australian Craniofacial Unit, Adelaide and the Erasmus Medical Centre, Rotterdam. METHODS: The database of both units was scrutinized and the case-notes of the patients with Nager syndrome were reviewed. Data was collected on patient demographics, surgical management, complications, and outcome. RESULTS: Nine patients (6âM:3âF) were identified with Nager syndrome, with a mean age at presentation of 3.7 years (range 8 days to 11.8 years). The mean follow-up time was 2.2 years (2 months to 19 years). SF3B4 mutation was noted in 2 patients and 1 patient had an X:9 translocation. Seven (77.8%) had obstructive sleep apnoea, with 5 patients diagnosed as severe obstructive sleep apnoea. Four patients had pollicization of their index, 2 patients had excision of extra radial digits and 1 patient underwent thumb duplication correction. Craniofacial surgery included mandibular advancement in 5 patients, temporo-mandibular joint reconstruction in 2 patients, and a genioplasty in 1 patient. CONCLUSION: Nager syndrome is a rare acrofacial dysostosis syndrome that is best managed within the realms of a multidisciplinary team. The authors would advocate early pollicization in patients with thumb anomalies to prevent any impairment in manual dexterity.
Assuntos
Avanço Mandibular , Disostose Mandibulofacial/cirurgia , Articulação Temporomandibular/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Comunicação Interdisciplinar , Colaboração Intersetorial , Masculino , Apneia Obstrutiva do Sono/cirurgia , Austrália do Sul , Adulto JovemRESUMO
OBJECTIVE: Our aims were to assess the prevalence of hypodontia in unilateral hemifacial microsomia (HFM), and to compare tooth (crown) size between affected and unaffected sides. DESIGN: In a retrospective cross-sectional study of South Australians, computed tomography (CT) scans were used to assess hypodontia and crown size (mesiodistal length, buccolingual width and crown height). The inclusion criteria were the absence of other congenital anomalies and the availability of CT scans. The exclusion criteria were the lack of extraction history or reproducible landmarks for morphometric assessment. The final sample comprised 41 participants in both dentitions, including 32 children and 9 adults (median age 13.9 years, range 0.4 - 47.6 years; 19 males and 22 females). Hypodontia was assessed in all participants, and the permanent crown size in 30 (73.2%) participants. Linear mixed-effects models were performed to determine if crown size was significantly different between the two sides, controlling for sex, HFM severity, and tooth and jaw type. RESULTS: Hypodontia occurred in none of the participants in the primary dentition, but in 6/30 (20%) participants in the permanent dentition (3/30 each on the affected and unaffected sides). There was no significant difference in the mean crown dimensions between the two sides, but the crown size was larger in males (p < 0.05), except for mesiodistal length, and became progressively smaller with increased HFM severity (p < 0.05). CONCLUSIONS: Hypodontia spared the primary dentition but featured prominently in the permanent dentition. The permanent crown dimensions were unaltered between the two sides.
Assuntos
Anodontia , Síndrome de Goldenhar , Masculino , Criança , Adulto , Feminino , Humanos , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Anodontia/diagnóstico por imagem , Anodontia/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Austrália , Coroa do Dente/diagnóstico por imagem , Odontometria , Coroas , TomografiaRESUMO
BACKGROUND: Achieving efficient introduction of plasmid DNA into primary cultures of mammalian cells is a common problem in biomedical research. Human primary cranial suture cells are derived from the connective mesenchymal tissue between the bone forming regions at the edges of the calvarial plates of the skull. Typically they are referred to as suture mesenchymal cells and are a heterogeneous population responsible for driving the rapid skull growth that occurs in utero and postnatally. To better understand the molecular mechanisms involved in skull growth, and in abnormal growth conditions, such as craniosynostosis, caused by premature bony fusion, it is essential to be able to easily introduce genes into primary bone forming cells to study their function. RESULTS: A comparison of several lipid-based techniques with two electroporation-based techniques demonstrated that the electroporation method known as nucleofection produced the best transfection efficiency. The parameters of nucleofection, including cell number, amount of DNA and nucleofection program, were optimized for transfection efficiency and cell survival. Two different genes and two promoter reporter vectors were used to validate the nucleofection method and the responses of human primary suture mesenchymal cells by fluorescence microscopy, RT-PCR and the dual luciferase assay. Quantification of bone morphogenetic protein (BMP) signalling using luciferase reporters demonstrated robust responses of the cells to both osteogenic BMP2 and to the anti-osteogenic BMP3. CONCLUSIONS: A nucleofection protocol has been developed that provides a simple and efficient, non-viral alternative method for in vitro studies of gene and protein function in human skull growth. Human primary suture mesenchymal cells exhibit robust responses to BMP2 and BMP3, and thus nucleofection can be a valuable method for studying the potential competing action of these two bone growth factors in a model system of cranial bone growth.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 3/farmacologia , Suturas Cranianas/citologia , Células-Tronco Mesenquimais/citologia , Transfecção/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Genes Reporter , Glipicanas/genética , Glipicanas/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Lipossomos/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Plasmídeos/genética , Plasmídeos/metabolismoRESUMO
Craniofacial phenomics has opened up numerous opportunities to correlate genetic and epigenetic factors to craniofacial phenotypes in order to improve our understanding of growth and development in health and disease. Three-dimensional (3D) imaging has played a key role in advancing craniofacial phenomics by facilitating highly sensitive and specific characterizations of craniofacial and dental morphology. Here we describe the use of micro-computed tomography (micro-CT) to image the murine craniofacial complex, followed by surface reconstruction for traditional morphometric analyses. We also describe the application of geometric morphometrics, based on Generalized Procrustes Analysis, for use in human premolars. These principles are interchangeable between various vertebrate species, and between various surface imaging techniques (including micro-CT and 3D surface scanners), offering a high level of versatility and precision for extensive phenotyping of the entire craniofacial complex.
Assuntos
Fenômica , Crânio , Animais , Humanos , Imageamento Tridimensional , Camundongos , Fenótipo , Crânio/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
OBJECTIVE: EFNB1 mutation causes craniofrontonasal dysplasia (CFND), a congenital syndrome associated with craniomaxillofacial anomalies characterised by coronal craniosynostosis, orbital hypertelorism, and midface dysplasia. The aim of this murine study was to investigate the effect of the EfnB1 conditional gene deletion in osteoprogenitor cells on the craniomaxillofacial skeletal morphology. DESIGN: The skulls of male and female mice, in which EfnB1 was deleted by Cre (a site-specific DNA recombinase) under the control of the Osterix (Osx) promoter (EfnB1OB-/-), were compared to those without EfnB1 deletion (Osx:Cre control) at two ages (4 and 8 weeks; n = 6 per group). The three-dimensional micro-computed tomography reconstructions were prepared to calculate 17 linear measurements in the cranial vault (brain box), midface and mandible. Coronal and sagittal sutures from the 8-week-old mice were also subjected to histological examination. RESULTS: EfnB1OB-/- mice displayed significantly larger cranial height, larger interorbital and nasal widths, smaller maxillary width than controls by 8 weeks (p < 0.05), but mandibular size was not significantly different (p > 0.05). Binomial testing showed significantly smaller EfnB1OB-/- skulls at 4 weeks but larger at 8 weeks (p < 0.05). Histological examination revealed increased bony fusion and fibrous connective tissue deposition at the coronal suture of EfnB1OB-/- mice compared with controls. CONCLUSIONS: Craniofacial phenotype of the murine model of EfnB1 deletion in osteoprogenitor cells partially represents the human CFND phenotype, with implications for better understanding mechanisms involved in skeletal morphogenesis and malocclusion.
Assuntos
Efrina-B1 , Desenvolvimento Maxilofacial , Crânio , Animais , Suturas Cranianas/diagnóstico por imagem , Modelos Animais de Doenças , Efrina-B1/genética , Face , Feminino , Masculino , Desenvolvimento Maxilofacial/genética , Camundongos , Fenótipo , Crânio/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
PURPOSE: Chordomas are rare slow growing, locally destructive tumours originating from remnants of the primitive notocord and are found most commonly in the clivus and saccrococcygeal region. These tumours usually present in early adult life but on occasion can present in childhood. The combination of the skull base location and paediatric patient size makes access to these tumours particularly challenging. METHODS AND RESULTS: We report a multidisciplinary technique used in two cases in children where a modified extended palatal split was undertaken to allow greater access for tumour excision. CONCLUSION: This approach allows for good access to the skull base region to allow for maximal tumour resection. This technique also appears to have minimal impact on palatal function and no adverse effects on the upper airway management.
Assuntos
Cordoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Palato/cirurgia , Neoplasias da Base do Crânio/cirurgia , Criança , Cordoma/patologia , Humanos , Lactente , Palato/patologia , Base do Crânio/patologia , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/patologiaRESUMO
BACKGROUND: : Management of patients with Treacher Collins syndrome is complicated and involves multiple disciplines working in concert to achieve a common outcome. This article reviews the experience at the Australian Craniofacial Unit and describes the protocol for management. METHODS: : Fifty patients were treated during the last 30 years. The records of these patients were reviewed to establish what interventions they required and how these fit into a protocol for management. RESULTS: : The protocol for management of Treacher Collins syndrome can be divided into 3 epochs. In the first epoch from birth to age 2, airway and feeding problems were the main focus. Four patients required tracheostomy. Of these, 1 died and the others received mandibular distraction. Hearing is evaluated and addressed early. Eleven patients (23%) required repair of a cleft palate. In the second epoch (aged 2-12 y), speech therapy is critical as is a focus on integrating into the education system. During this epoch, reconstruction of the upper face was performed either with bone grafts or with vascularized bone flaps. Both required repeat bone grafts later. In the third epoch (aged 13-18 y), orthognathic surgery was performed. Revision surgery and further bone grafting were performed again at around age 18. Patients reported being generally happy with their appearance and with few exceptions were able to complete education, gain employment, and feel socially accepted. CONCLUSIONS: : Management of patients with Treacher Collins syndrome should be through a multidisciplinary protocol to achieve good results while minimizing confusion and unnecessary surgery.
Assuntos
Disostose Mandibulofacial/terapia , Adolescente , Austrália , Criança , Pré-Escolar , Protocolos Clínicos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Equipe de Assistência ao Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: Saethre-Chotzen Syndrome (SCS) is an autosomal dominant syndrome that occurs due to a mutation or deletion of the Twist1 gene at chromosome 7p21. Our aim was to conduct a morphometric analysis of the craniofacial features in the mouse associated with a Twist1+/- mutation. METHODS: Micro-computed imaging was conducted for the skulls of forty skeletally mature mice, equally distributed by sex (male and female) and two genotypes (Twist1+/- or murine model of SCS; and Twist1+/+ or wild-type). A morphometric analysis was carried out for eight parameters for the maxillary-zygomatico-temporal region, 10 parameters for the mandible and three parameters for teeth from three-dimensional reconstructions. RESULTS: Compared with wild-type, the murine model of SCS showed these trends: (1) maxillary-zygomatico-temporal region, significantly shorter length and width posteriorly (p<0.05), (2) mandible, significantly reduced height and width (p<0.05), and (3) teeth, significantly shorter height, shorter mesio-distal width but longer bucco-lingual width (p<0.05). In the murine model of SCS, the key morphological variations included incomplete ossification of the temporal bone and zygomatic arch, twisting and/or incomplete ossification of the palatal process of the maxilla, premaxilla and the ventral nasal concha, as well as bifid coronoid processes. CONCLUSIONS: The skeletal and dental alterations in the height, length and width provide a foundation for large-scale phenomics studies, which will improve existing knowledge of the Twist1 signalling cascade. This is relevant given the predicted shift towards minimally invasive molecular medical treatment for craniosynostosis.
Assuntos
Acrocefalossindactilia/patologia , Anormalidades Craniofaciais/genética , Proteína 1 Relacionada a Twist/genética , Acrocefalossindactilia/genética , Animais , Anormalidades Craniofaciais/patologia , Feminino , Deleção de Genes , Masculino , Camundongos , MutaçãoRESUMO
OBJECTIVES: Fibroblast growth factor receptor 2 (FGFR2) C342Y/+ mutation is a known cause of Crouzon syndrome that is characterised by craniosynostosis and midfacial hypoplasia. Our aim was to conduct extensive phenotyping of the maxillary, mandibular and dental morphology associated with this mutation. MATERIALS AND METHODS: Morphometric data were obtained from 40 mice, representing two genotypes (Crouzon and wild-type) and two sexes (males and females) (n=10 in each group). Dental analysis further categorised the first molars into the two jaws (maxillary and mandibular) (n=20 in each group). Maxillary, mandibular and dental morphology was compared by analysing 23 linear landmark-based dimensions in three-dimensional micro-computed tomography reconstructions. RESULTS: Compared with wild-type, Crouzon (FGFR2C342Y/+) maxillae were significantly shorter in maximum height, anterior and posterior lengths and middle width, but larger in posterior width (p<0.05 for height; p<0.001 for other comparisons). In the Crouzon mandible, the ascending and descending heights, effective and mandibular lengths, and intercoronoid and intercondylar widths were significantly shorter, whereas intergonial width was larger (p<0.01 for intercondylar width; p<0.001 for other comparisons). Crouzon teeth were significantly smaller mesiodistally, but larger in crown height (p<0.001 for each comparison). All Crouzon mice presented with bifid mandibular condyles and a quarter presented with expansive bone lesions in the mandibular incisor alveolus. CONCLUSIONS: Our findings of hypoplasia in all three planes in Crouzon maxillae and mandibles, together with the presence of bifid mandibular condyles and expansive bone lesions, may be relevant to maxillofacial surgery and orthodontics. Beyond skeletal effects, the FGFR2C342Y/+ mutation is now implicated in affecting tooth development. This study's skeletal phenomics data also provides baseline data against which the effect of various treatments can now be assessed.
Assuntos
Disostose Craniofacial/patologia , Mandíbula/patologia , Maxila/patologia , Animais , Disostose Craniofacial/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Genótipo , Imageamento Tridimensional , Masculino , Mandíbula/diagnóstico por imagem , Maxila/diagnóstico por imagem , Camundongos , Fenótipo , Microtomografia por Raio-XRESUMO
Titania nanotubes (TNTs) engineered on titanium (Ti) surfaces (i.e. TNT/Ti) and loaded with specific drugs have been recognised as a promising solution for localised therapeutic delivery to address several medical problems not feasible with conventional drug administration. We propose the use of TNT/Ti protein-releasing implants to treat paediatric craniofacial abnormality in craniosynostosis caused by premature fusion of cranial sutures. In this study, we have analysed the biological response of human suture mesenchymal cells (SMCs), extracted from two different patients undergoing craniofacial reconstruction surgery, at the TNT/Ti implant surface. The experimental groups included large-diameter TNT/Ti implants, with and without biopolymer surface coating (Chitosan and Pluronic-F127) while the controls comprised of flat Ti disc and tissue culture plastic. The non-loaded implant surfaces and the cellular interactions at the implant-cell interface were characterised using scanning electron microscopy (SEM). The SMC adhesion, viability and proliferation were determined by MTT assay and manual cell counting at day 1 and day 3 of cell incubation. SEM showed significant reduction in initial attachment and adhesion of SMCs at TNT-cell biointerface compared with the control Ti discs. Subsequent cell proliferation results also revealed a decrease in the number of viable cells on the TNT surfaces. The nanotopography and structural features along with the surface chemistry dictated the cellular response, with nanotubular surfaces (with and without polymer coating) impeding cell adhesion and proliferation. Our findings hold promise for the use of TNT-based cranial implants as a delivery system to prevent sutural bone growth for advanced craniosynostosis therapy.
Assuntos
Técnicas de Cultura de Células , Suturas Cranianas/cirurgia , Craniossinostoses/terapia , Células-Tronco Mesenquimais/citologia , Nanotubos/química , Titânio/química , Adesão Celular , Linhagem da Célula , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Humanos , Lactente , Teste de Materiais , Microscopia Eletrônica de Varredura , Polímeros/química , Próteses e Implantes , Propriedades de SuperfícieRESUMO
BACKGROUND: The potential problem of growth anomalies affecting a mandible following a fracture of a mandibular condyle in childhood is well established. However, there have been no previous reports of this phenomenon affecting other fracture sites in the mandible. PATIENTS: Two patients who had parasymphyseal fractures treated in childhood presented at skeletal maturity with hyperostosis at the fracture site, producing chin asymmetry in their teens. RESULTS: In both cases the hyperostosis produced significant chin asymmetry without disturbance of the occlusion. Both patients were managed with corrective genioplasty. CONCLUSION: These cases reinforce the previous recommendations regarding the need for long-term follow-up of children who sustain facial fractures of the mandible, and that the protocol should be expanded to include parasymphyseal fractures as well as fractures of the condyle.