RESUMEN
Congenital craniofacial abnormalities are congenital anomalies of variable expressivity and severity with a recognizable set of abnormalities, which are derived from five identifiable primordial structures. They can occur unilaterally or bilaterally and include various malformations such as cleft lip with/without palate, craniosynostosis, and craniofacial microsomia. To date, the molecular etiology of craniofacial abnormalities is largely unknown. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, circular RNAs and PIWI-interacting RNAs, function as major regulators of cellular epigenetic hallmarks via regulation of various molecular and cellular processes. Recently, aberrant expression of ncRNAs has been implicated in many diseases, including craniofacial abnormalities. Consequently, this review focuses on the role and mechanism of ncRNAs in regulating craniofacial development in the hope of providing clues to identify potential therapeutic targets.
Asunto(s)
Anomalías Craneofaciales , Craneosinostosis , MicroARNs , ARN Largo no Codificante , Humanos , ARN no Traducido/genética , MicroARNs/genética , Anomalías Craneofaciales/genéticaRESUMEN
PURPOSE: To evaluate the role of anatomic alterations of the upper airway and facial skeleton in the evolution of obstructive sleep apnea (OSA) in a prospective population-based study with an 8-year follow-up. METHODS: This was a population-based, longitudinal, prospective study, which took place from 2007 to 2015 at the Instituto do Sono, Sao Paulo, Brazil. In 2007, type I polysomnography (PSG), otorhinolaryngological examination, and collection of anthropometric measurements of all volunteers were performed. Volunteers were classified according to their anatomical features of the upper airway and facial skeleton. After 8 years, volunteers were invited for reevaluation. The relationship between anatomical characteristics and polysomnographic evolution was evaluated. RESULTS: The study included 554 patients. After 8 years of follow-up, there was an increase in neck circumference and body mass index of the participants. There was a worsening in all polysomnographic parameters analyzed, with an increase in the apnea-hypopnea index, a decrease in minimum saturation values, and an increase in the percentage of sleep time with peripheral oxyhemoglobin saturation <90%. There was no statistical relationship between the anatomical findings considered unfavorable and the worsening of polysomnographic parameters. CONCLUSIONS: In a sample of the general population, after 8 years, we did not find any relationship between upper airway and facial skeleton characteristics and the progression of OSA.
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Apnea Obstructiva del Sueño , Humanos , Estudios Prospectivos , Estudios de Seguimiento , Brasil , Apnea Obstructiva del Sueño/diagnóstico , CaraRESUMEN
Cloverleaf skull deformity or Kleeblattschadel syndrome is a severe condition where multiple cranial sutures are absent and prematurely fused, leading to a trilobate head shape. The remaining open sutures or fontanelles compensate for rapid brain expansion, while the constricted fused calvarium restricts brain growth and results in increased intracranial pressure. Recent data show that early posterior cranial and foramen magnum decompression positively affects infants with cloverleaf skulls. However, long-term sequelae are still rarely discussed. We hereby report a child who developed secondary metopic craniosynostosis after posterior cranial decompression, which required a front-orbital advancement and cranial remodelling as a definitive procedure.
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Craneosinostosis , Descompresión Quirúrgica , Humanos , Craneosinostosis/cirugía , Craneosinostosis/complicaciones , Descompresión Quirúrgica/métodos , Lactante , Masculino , Discapacidad Intelectual/etiología , Discapacidad Intelectual/cirugía , Anomalías Craneofaciales/cirugía , Anomalías Craneofaciales/complicaciones , FemeninoRESUMEN
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.
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Fisura del Paladar , Anomalías Craneofaciales , Craneosinostosis , Ratones , Masculino , Femenino , Animales , Fisura del Paladar/genética , Microtomografía por Rayos X , Factor 10 de Crecimiento de Fibroblastos/genética , Modelos Animales de Enfermedad , Anomalías Craneofaciales/diagnóstico por imagen , Anomalías Craneofaciales/genética , Craneosinostosis/genética , Mutación/genéticaRESUMEN
BACKGROUND: Aiming to measure and compare asymmetry of facial hard and soft tissues in patients with HFM and isolated microtia, examining how it evolves. METHODS: This cross-sectional study assessed facial asymmetry in male East Asian patients aged 5-12 diagnosed with unilateral hemifacial microsomia (Pruzansky-Kaban types I and IIA) or isolated microtia. Using 3D imaging of computed tomography scans, it measured root-mean-square (RMS) values for surface deviations across facial regions. Statistical analyses explored differences between conditions and the relationship of age with facial asymmetry. RESULTS: A total of 120 patients were categorized into four groups by condition (HFM or isolated microtia) and age (5-7 and 8-12 years). Patients with HFM exhibited the greatest asymmetry in the lower cheek, while those with isolated microtia showed primarily upper face asymmetry. Significant differences, except in the forehead and nasal soft tissue, were noted between the groups across age categories. Notable distinctions in hard tissue were found between age groups in the nasal and mid-cheek areas for patients with HFM (median RMS (mm) 0.9 vs. 1.1, P = 0.02; 1.5 vs. 1.7, P = 0.03) and in the nasal and upper lip areas for patients with isolated microtia (median RMS (mm) 0.8 vs. 0.9, P = 0.002; 0.8 vs. 1.0, P = 0.002). Besides these areas for HFM, no significant age-asymmetry correlation was detected. CONCLUSIONS: Significant differences in facial asymmetry were observed between HFM and isolated microtia, with the asymmetry in specific area evolving over time. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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BACKGROUND: This paper aimed to explore the prevalence of temporomandibular disorders (TMDs) signs/symptoms, and to investigate the possible link between signs/symptoms of TMDs and mouth breathing (MB) by evaluating along with other risk factors, in a Turkish subpopulation of children and adolescence. METHODS: This study was conducted with the archival data of the patients who applied with orthodontic complaints. Data on demographic characteristics, family-related factors, systemic status, occlusion, breathing patterns, oral habits, and bruxism were retrieved from the archival records. RESULTS: Nine hundred forty-five children and adolescents with a mean age of 14.82 ± 2.06 years were included in the study. Of the participants, 66% were girls, 60.4% were delivered by C-section, 8.4% of the participants had at least one systemic disease, 9.2% of the participants had allergy, and 4.3% of the participants' parents were divorced, 18.7% have an oral habit, 6.6% have bruxism, 29.8% have malocclusion and 14.1% have MB. Eight-point-five percent of participants have signs/symptoms of TMD. Among them 2.9% have pain, 3.7% have joint sounds, 1.4% have deflection, and 3.9% have deviation. Evaluation of the risk factors revealed a significant relation between the signs/symptoms of TMD and bruxism (OR 8.07 95% CI 4.36-14.92), gender (OR 2.01 95% CI 1.13-3.59), marital status of parents (OR 2.62 95% CI 1.07-6.42), and MB (OR 3.26 95% CI 1.86-5.71). CONCLUSIONS: According to the study's findings, girls and those with bruxism, divorced parents, and MB behavior are more likely to have signs/symptoms of TMD. Age found to have significant effect on the occurrence of the signs/symptoms of TMD alone, but together with other factors the effect of the age is disappeared. Early screening and intervention of MB as well as the signs/symptoms of TMD can help to limit detrimental effects of these conditions on growth, and quality of life of children and adolescents.
Asunto(s)
Respiración por la Boca , Trastornos de la Articulación Temporomandibular , Humanos , Femenino , Adolescente , Masculino , Turquía/epidemiología , Estudios Transversales , Trastornos de la Articulación Temporomandibular/epidemiología , Niño , Respiración por la Boca/epidemiología , Respiración por la Boca/complicaciones , Factores de Riesgo , Prevalencia , Bruxismo/epidemiología , Bruxismo/complicaciones , Maloclusión/epidemiología , Maloclusión/complicaciones , Dolor Facial/epidemiología , Hipersensibilidad/epidemiología , Hipersensibilidad/complicacionesRESUMEN
BACKGROUND: Parameningeal rhabdomyosarcoma (PM-RMS) is a rare and aggressive soft tissue malignancy that primarily occurs in the head and neck region. The standard treatment approach for RMS involves a multimodal therapy regimen, which includes surgery, chemotherapy, and radiotherapy. However, the routine use of radiotherapy and chemotherapy in young patients with RMS in the head and neck region can lead to adverse effects on dental development and thereby, pose a challenge in planning dental intervention. CASE PRESENTATION: This case report outlines the dental and facial developmental consequences in a 13-year-old child, who received chemo-radiotherapeutic intervention at the age of 7 years for the management of PM-RMS. Following treatment, the child exhibited significant dental complications, including arrested root growth and restricted mouth opening. CONCLUSIONS: This case highlights the necessity for interdisciplinary collaboration between oncologists, dentists, and other healthcare professionals to mitigate the adverse effects on dental health and overall quality of life in patients undergoing chemo-radiotherapy for rhabdomyosarcoma.
Asunto(s)
Rabdomiosarcoma , Humanos , Adolescente , Rabdomiosarcoma/complicaciones , Rabdomiosarcoma/terapia , Masculino , Raíz del Diente/anomalías , Raíz del Diente/diagnóstico por imagen , Dentición PermanenteRESUMEN
PURPOSE: Data supporting treatment recommendations for congenital nasolacrimal duct obstruction (CNLDO) in patients with craniofacial abnormalities is scarce. This study reports the incidence, clinical features, and outcomes of patients with concomitant craniofacial abnormalities and CNLDO. METHODS: This multi-center, retrospective, population-based cohort study included all patients diagnosed with CNLDO before age 6 during a 10-year period in a single US county. RESULTS: Of the 17,713 live births during the study period, 1998 infants were diagnosed with CNLDO, among whom 41 (2.05%) had associated congenital craniofacial abnormalities, yielding a birth prevalence of 23.1 (95% CI 16.6-31.4) per 10,000 live births. Craniofacial patients were significantly older at time of diagnosis (6.2 months) compared to uncomplicated CNLDO (3.7 months; p = 0.035). There was no significant difference in mean age at spontaneous CNLDO resolution, but 31.7% of craniofacial patients required probing for CNLDO resolution, compared to 14.5% in the CNLDO group (OR 2.76 [95%CI 1.41-5.39] p = 0.003). All but two patients with craniofacial abnormalities had resolution of symptoms after initial probing. Intraoperative probing findings indicated that 8 of 13 craniofacial patients had complex obstructions. CONCLUSIONS: The similar age at spontaneous resolution indicates that watchful waiting until approximately one year of age is a reasonable approach even in patients with craniofacial abnormalities, though more of these patients may require surgical intervention.
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MN1 was originally identified as a tumor-suppressor gene. Knockout mouse studies have suggested that Mn1 is associated with craniofacial development. However, no MN1-related phenotypes have been established in humans. Here, we report on three individuals who have de novo MN1 variants that lead to a protein lacking the carboxyl (C) terminus and who presented with severe developmental delay, craniofacial abnormalities with specific facial features, and structural abnormalities in the brain. An in vitro study revealed that the deletion of the C-terminal region led to increased protein stability, an inhibitory effect on cell proliferation, and enhanced MN1 aggregation in nuclei compared to what occurred in the wild type, suggesting that a gain-of-function mechanism is involved in this disease. Considering that C-terminal deletion increases the fraction of intrinsically disordered regions of MN1, it is possible that altered phase separation could be involved in the mechanism underlying the disease. Our data indicate that MN1 participates in transcriptional regulation of target genes through interaction with the transcription factors PBX1, PKNOX1, and ZBTB24 and that mutant MN1 impairs the binding with ZBTB24 and RING1, which is an E3 ubiquitin ligase. On the basis of our findings, we propose the model that C-terminal deletion interferes with MN1's interaction molecules related to the ubiquitin-mediated proteasome pathway, including RING1, and increases the amount of the mutant protein; this increase leads to the dysregulation of MN1 target genes by inhibiting rapid MN1 protein turnover.
Asunto(s)
Encefalopatías/etiología , Anomalías Craneofaciales/etiología , Mutación con Ganancia de Función , Regulación de la Expresión Génica , Eliminación de Secuencia , Transactivadores/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Encefalopatías/patología , Proliferación Celular , Niño , Preescolar , Anomalías Craneofaciales/patología , Femenino , Células HeLa , Humanos , Masculino , Proteolisis , Síndrome , Transactivadores/metabolismo , Transcriptoma , Proteínas Supresoras de Tumor/metabolismoRESUMEN
PURPOSE: To evaluate craniofacial measurements on 3D-stereophotogrammetry and see if particular measurements are more typical in obstructive sleep apnea (OSA) and have a correlation with its severity. METHODS: Subjects included were adults undergoing a diagnostic polysomnography. Age, BMI, neck, abdominal and hip circumference (cm) were recorded. 3D-stereophotogrammetry was performed and landmarks were placed on the 3D-image. Different linear, angular and volume measurements were performed to gauge facial and neck anatomy. The relationship between these measurements and the severity of OSA, based on the obstructive apnea/hypopnea index (OAHI, events/h), was assessed by multiple linear regression, and adjusted for BMI and sex. RESULTS: Of 91 subjects included (61 male), mean age was 46 ± 12 years, BMI 30.1 ± 6.5 kg/m2, OAHI 19.3 ± 18.8/h. BMI was higher (p = 0.0145) in females (32.9 ± 7.7) than in males (28.6 ± 5.3). This was also true for hip circumference (118 ± 15 vs 107 ± 10, p = 0.0006), while the neck circumference was higher (p < 0.0001) in males (41 ± 4 vs 37 ± 4). The following parameters could predict the logOAHI (r2-adjusted = 0.51): sex (p < 0.0001), BMI (p = 0.0116), neck-depth/mandibular-length (p = 0.0002), mandibular-width angle (p = 0.0118), neck-depth euclidean distance/surface distance (E/S) (p = 0.0001) and the interaction terms between sex and neck-depth/mandibular-length (p = 0.0034), sex and neck-depth E/S (p = 0.0276) and BMI and neck-depth E/S (p = 0.0118). The interaction between sex and neck-depth/mandibular-length showed a steeper linear course in females. This is also true for the interaction term BMI with neck-depth E/S in patients with a higher BMI. With a same neck-depth ratio, the OAHI is larger in men. CONCLUSION: Measurements involving the width of the face and addressing the soft tissue in the upper neck were found to have a significant relation with OSA severity. We found remarkable differences between non-obese/obese subjects and between males and females.
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Apnea Obstructiva del Sueño , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Masa Corporal , Antropometría , Apnea Obstructiva del Sueño/diagnóstico , Polisomnografía , SueñoRESUMEN
Multisuture craniosynostosis is associated with a number of syndromes and underlying gene mutations. It is rarely caused by chromosome disorders. For the management, multisuture craniosynostosis raises concerns about abnormal head shape and risks of increased intracranial pressure in affected patients. Calvarial reconstruction to reshape the skull shape and expand the intracranial volume plays an essential role in correcting particular problems. Here, we report a 2-month-old female infant presenting with low birth weight, abnormal head shape, dysmorphic facies and pinnae, hypotonia, and feeding difficulty. Three-dimensional computed tomographic scans revealed left unicoronal and sagittal synostoses. Chromosome microarray analysis revealed de novo chromosome 14q32.12-q32.31 deletion. Among the deleted genes, YY1 and BCL11B are the most likely candidate genes causing craniosynostosis. Some clinical features of the patient are similar to Temple syndrome indicating that the deleted region is paternal in origin. In summary, this is a rare case of chromosome 14q32 deletion with multisuture craniosynostosis. We also report the multidisciplinary management and clinical outcomes after early cranial vault remodelling procedures.
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Craneosinostosis , Hipertensión Intracraneal , Lactante , Humanos , Femenino , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/genética , Craneosinostosis/cirugía , Cráneo/cirugía , Tomografía Computarizada por Rayos X , Hipertensión Intracraneal/etiología , Deleción Cromosómica , Cromosomas , Proteínas Represoras/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
The cloverleaf skull deformity remains among the most complicated craniofacial conditions to successfully manage. Many cases achieve largely unsatisfactory outcomes due to the requirement for frequent reoperation on the cranial vault and failure to deal with all the elements of the craniofaciostenosis in a timely fashion. Early cranial vault surgery without addressing the cranial base deformity and its attendant cerebrospinal fluid flow changes is invariably challenging and disappointing. A recent focus on the expansion of the posterior cranial vault as a primary procedure with the greater volume change allows a delay in fronto-orbital advancement and reduced need for repeat surgery. We herein describe three cases of complex multisuture craniosynostosis with cloverleaf skull deformity who underwent neonatal posterior cranial vault decompression along with foramen magnum decompression. Our report examines the safety and rationale for this pre-emptive surgical approach to simultaneously deal with the cranial vault and craniocervical junction abnormalities and thus change the early trajectory of these complex cases.
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Craneosinostosis , Recién Nacido , Humanos , Lactante , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Cráneo/diagnóstico por imagen , Cráneo/cirugía , ReoperaciónRESUMEN
BACKGROUND: Bone remodelling during development and growth is important for craniofacial integrity of offspring. The aim of this study was to investigate the changes in offspring adult skull morphology when the osteoclasts number was altered in utero, using three-dimensional (3D) geometric morphometric analysis (GMA). MATERIALS AND METHODS: We altered osteoclasts number in utero via two approaches. First, we generated heterozygous CtskCre ;DTAfl/+ (diphtheria toxin A) mice. Second, we altered Ctsk expression in vivo by injecting pregnant wild-type dams at embryonic day (E) 12.5 with in vivo siRNA specific for Ctsk. Mice were collected at 6 weeks and analysed using geometric morphometric analysis via computed tomography, histomorphometry and gene expression analysis. RESULTS: Altering osteoclasts number in utero affected the offspring adult skull morphology. Decreased Ctsk and osteoclast numbers were associated with a decrease in cranial vault height and an increase in mandibular body length. Changes in size and shape were observed with an increased number of osteoclasts in CtskCre ;DTAfl/+ mice, including an increase in cranial vault height, as well as a shortening of mandibular body length and ramus height. CONCLUSION: The findings of this study suggest that modulation of osteoclast numbers during pre- and post-natal development may be a previously unknown factor in the aetiology of skeletal malocclusions. An improved understanding of the factors affecting bone homeostasis during development and growth may help in the development of future therapies that would target the early intervention of skeletal malocclusion.
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Osteoclastos , Diente , Animales , Femenino , Ratones , Embarazo , Remodelación Ósea/genética , Osteoclastos/metabolismo , Cráneo/diagnóstico por imagenRESUMEN
Endocrine disrupting chemicals (EDCs) can interact with native hormone receptors to interfere with and disrupt hormone signalling that is necessary for a broad range of developmental pathways. EDCs are pervasive in our environment, in particular in our waterways, making aquatic wildlife especially vulnerable to their effects. Many of these EDCs are able to bind to and activate oestrogen receptors, causing aberrant oestrogen signalling. Craniofacial development is an oestrogen-sensitive process, with oestrogen receptors expressed in chondrocytes during critical periods of development. Previous studies have demonstrated a negative effect of high concentrations of oestrogen on early craniofacial patterning in the aquatic model organism, the zebrafish (Danio rerio). In order to determine the impacts of exposure to an oestrogenic EDC, we exposed zebrafish larvae and juveniles to either a high concentration to replicate previous studies, or a low, environmentally relevant concentration of the oestrogenic contaminant, 17α-ethinylestradiol. The prolonged / chronic exposure regimen was used to replicate that seen by many animals in natural waterways. We observed changes to craniofacial morphology in all treatments, and most strikingly in the larvae-juveniles exposed to a low concentration of EE2. In the present study, we have demonstrated that the developmental stage at which exposure occurs can greatly impact phenotypic outcomes, and these results allow us to understand the widespread impact of oestrogenic endocrine disruptors. Given the conservation of key craniofacial development pathways across vertebrates, our model can further be applied in defining the risks of EDCs on mammalian organisms.
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Disruptores Endocrinos , Contaminantes Químicos del Agua , Animales , Etinilestradiol/toxicidad , Pez Cebra , Receptores de Estrógenos , Estrógenos , Estrona , Disruptores Endocrinos/toxicidad , Contaminantes Químicos del Agua/toxicidad , MamíferosRESUMEN
Proboscis lateralis is a rare craniofacial anomaly in which a rudimentary nasal appendage arises at the medial canthal area. The severity depends on organ involvement, including eyes, nose, cleft lip/palate, and/or concomitant intracranial anomalies. Here, we present a child with proboscis lateralis and associated trans-ethmoidal encephalocele. We suggest doing the preoperative CT and/or MRI to rule out associated intracranial anomalies and reliably preoperative planning tools. Moreover, we proposed an alternative nasal reconstructive technique using a composite graft from the proboscis mass at the same time as encephalocele repair with promising results.
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Anomalías Múltiples , Labio Leporino , Fisura del Paladar , Enfermedades Nasales , Anomalías del Sistema Respiratorio , Niño , Humanos , Anomalías Múltiples/cirugía , Labio Leporino/diagnóstico por imagen , Labio Leporino/cirugía , Labio Leporino/complicaciones , Fisura del Paladar/cirugía , Encefalocele/diagnóstico por imagen , Encefalocele/cirugía , Encefalocele/complicaciones , Nariz/diagnóstico por imagen , Nariz/cirugía , Nariz/anomalíasRESUMEN
INTRODUCTION: The concept of "overcorrection" for trigonocephaly has been reported to achieve both anterior cranial fossa expansion and normalization of craniofacial form. The purpose of this study is to describe in detail a standardized technique to fronto-orbital advancement utilizing the concept of "overcorrection" and objectively evaluate intermediate results. METHODS: This retrospective study included patients with isolated metopic synostosis who underwent surgery via the proposed surgical technique and age and sex-matched unaffected controls. Craniofacial morphometric analysis was performed on pre-, immediate post-, and intermediate postoperative (>2 years) three-dimensional (3D)-rendered computed tomographic (CT) scans and photographs. Key CT-based measurements included interzygomaticofrontal suture distance (IZFS), endocranial bifrontal angle (ECA), and temporal expansion. 3D photogrammetry was performed using established measurements and associated Z-scores converted. A Paired t-test and analysis of variance were performed when appropriate. RESULTS: Forty-one patients were included. A comparison of pre- and immediate postoperative CT scans demonstrated statistically significant increases in all measurements. Subset analysis of 12 patients with intermediate follow-up (age: 39.6 ± 3.6 months) demonstrated significant differences from preoperative values except for IZFS, which decreased from immediate postoperative values and was smaller than age- and sex-matched controls. 3D photogrammetry demonstrated a mean Z-score above the norm for frontal breath. 3D photogrammetry is also positively correlated with CT-based measurements. CONCLUSIONS: This standardized "overcorrection" approach for trigonocephaly can provide the appropriate changes to maintain a normal ECA despite a reduction in bifrontal width over time. 3D photogrammetry positively correlated with CT-based measurements and may provide useful information when following patients clinically. Long-term follow-up assessment to determine the necessary degree of overcorrection at skeletal mature is needed.
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Craneosinostosis , Imagenología Tridimensional , Procedimientos de Cirugía Plástica , Preescolar , Humanos , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The developmental disorder Burn-McKeown Syndrome (BMKS) is characterised by choanal atresia and specific craniofacial features. BMKS is caused by biallelic variants in the pre-messenger RNA splicing factor TXNL4A. Most patients have a loss-of-function variant in trans with a 34-base pair (bp) deletion (type 1 Δ34) in the promoter region. Here, we identified two patients with BMKS. One individual has a TXNL4A c.93_94delCC, p.His32Argfs *21 variant combined with a type 1 Δ34 promoter deletion. The other has an intronic TXNL4A splice site variant (c.258-3C>G) and a type 1 Δ34 promoter deletion. We show the c.258-3C>G variant and a previously reported c.258-2A>G variant, cause skipping of the final exon of TXNL4A in a minigene splicing assay. Furthermore, we identify putative transcription factor binding sites within the 56 bp of the TXNL4A promoter affected by the type 1 and type 2 Δ34 and use dual luciferase assays to identify a 22 bp repeated motif essential for TXNL4A expression within this promoter region. We propose that additional variants affecting critical transcription factor binding nucleotides within the 22 bp repeated motif could be relevant to BMKS aetiology. Finally, our data emphasises the need to analyse the non-coding sequence in individuals where a single likely pathogenic coding variant is identified in an autosomal recessive disorder consistent with the clinical presentation.
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Atresia de las Coanas/diagnóstico , Atresia de las Coanas/genética , Sordera/congénito , Genotipo , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Mutación , Ribonucleoproteína Nuclear Pequeña U5/genética , Alelos , Sitios de Unión , Sordera/diagnóstico , Sordera/genética , Facies , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Linaje , Fenotipo , Regiones Promotoras Genéticas , Unión Proteica , Empalme del ARN , Ribonucleoproteína Nuclear Pequeña U5/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Tessier number 3 craniofacial clefts are a rare congenital deformity of the oronasoocular region with variable severity, most often with serious impacts on appearance and function due to involvement of the bone and soft tissue. However, they can occasionally manifest mildly as a skin-colored congenital facial papule present with subtle anatomic anomalies and signs of deeper involvement, such as crusting and oozing. Recognizing that a congenital facial papule, including non-midline lesions, may be the presenting sign of an underlying developmental anomaly is important to avoid missing the diagnosis of a more extensive underlying congenital defect. We present a rare case of a forme fruste variant of a Tessier number 3 craniofacial cleft to raise awareness of its presentation and advise initial management in hopes of improving outcomes.
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Anomalías Craneofaciales , Anomalías Cutáneas , Humanos , Anomalías Craneofaciales/diagnóstico , Cara/anomalíasRESUMEN
OBJECTIVE: To evaluate the association between orofacial clefts (OFC) and tooth abnormalities (TA). METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Library, LILACS, and BBO, and in the gray literature and selected observational studies that evaluated the association between TA and OFC. The risk of bias was analyzed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed comparing the presence and absence of OFC, cleft type-cleft palate (CP) and cleft lip with or without palate (CL/P)-and cleft laterality-unilateral and bilateral. The certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 99 studies were included in the qualitative analysis, and 37 were included in the meta-analysis. Only four studies were classified as low risk of bias. Significant associations were observed between the presence of OFC and tooth agenesis (OR = 19.46; 95%CI = 4.99-75.96), supernumerary teeth (OR = 4.04; 95%CI = 1.26-12.99), developmental defects of enamel (OR = 3.15; 95%CI = 1.28-7.80), microdontia (OR = 15.57; 95%CI = 1.06-228.51), and taurodontism (OR = 1.74; 95%CI = 1.74-2.86). Individuals with CP had a lower frequency of supernumerary teeth (OR = 0.22; 95%CI = 0.08-0.64), peg-shaped tooth (OR = 0.31; 95%CI = 0.12-0.80), and morphological TA (OR = 0.13; 95%CI = 0.04-0.45) than individuals with CL/P. No TA was significantly associated with cleft laterality (p > 0.05). The quality of the evidence was very low in all analyses. CONCLUSION: Individuals with OFC had a higher frequency of TA than those without OFC. Individuals with CP had a lower frequency of TA than individuals with CL/P. No TA was associated to cleft laterality. CLINICAL RELEVANCE: Help to identify the treatment needs of individuals affected by OFC, improving the services provided to this population.
Asunto(s)
Labio Leporino , Fisura del Paladar , Anomalías Dentarias , Diente Supernumerario , Labio Leporino/complicaciones , Labio Leporino/epidemiología , Fisura del Paladar/complicaciones , Fisura del Paladar/epidemiología , Humanos , Anomalías Dentarias/complicaciones , Anomalías Dentarias/epidemiología , Diente Supernumerario/complicacionesRESUMEN
Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.