Tissue-nonspecific Alkaline Phosphatase Deficiency Causes Abnormal Craniofacial Bone Development in the Alpl−/− Mouse Model of Infantile Hypophosphatasia

PubMed Central

Liu, Jin; Nam, Hwa Kyung; Campbell, Cassie; Gasque, Kellen Cristina da Silva; Millán, José Luis; Hatch, Nan E.

2014-01-01

Tissue-nonspecific alkaline phosphatase (TNAP) is an enzyme present on the surface of mineralizing cells and their derived matrix vesicles that promotes hydroxyapatite crystal growth. Hypophosphatasia (HPP) is an inborn-error-of-metabolism that, dependent upon age of onset, features rickets or osteomalacia due to loss-of function mutations in the gene (Alpl) encoding TNAP. Craniosynostosis is prevalent in infants with HPP and other forms of rachitic disease but how craniosynostosis develops in these disorders is unknown. Objectives: Because craniosynostosis carries high morbidity, we are investigating craniofacial skeletal abnormalities in Alpl−/− mice to establish these mice as a model of HPP-associated craniosynostosis and determine mechanisms by which TNAP influences craniofacial skeletal development. Methods: Cranial bone, cranial suture and cranial base abnormalities were analyzed by micro-CT and histology. Craniofacial shape abnormalities were quantified using digital calipers. TNAP expression was suppressed in MC3T3E1(C4) calvarial cells by TNAP-specific shRNA. Cells were analyzed for changes in mineralization, gene expression, proliferation, apoptosis, matrix deposition and cell adhesion. Results: Alpl−/− mice feature craniofacial shape abnormalities suggestive of limited anterior-posterior growth. Craniosynostosis in the form of bony coronal suture fusion is present by three weeks after birth. Alpl−/− mice also exhibit marked histologic abnormalities of calvarial bones and the cranial base involving growth plates, cortical and trabecular bone within two weeks of birth. Analysis of calvarial cells in which TNAP expression was suppressed by shRNA indicates that TNAP deficiency promotes aberrant osteoblastic gene expression, diminished matrix deposition, diminished proliferation, increased apoptosis and increased cell adhesion. Conclusions: These findings demonstrate that Alpl−/− mice exhibit a craniofacial skeletal phenotype similar to that seen in infants with HPP, including true bony craniosynostosis in the context of severely diminished bone mineralization. Future studies will be required to determine if TNAP deficiency and other forms of rickets promote craniosynostosis directly through abnormal calvarial cell behavior, or indirectly due to deficient growth of the cranial base. PMID:25014884

Facial Phenotyping by Quantitative Photography Reflects Craniofacial Morphology Measured on Magnetic Resonance Imaging in Icelandic Sleep Apnea Patients

PubMed Central

Sutherland, Kate; Schwab, Richard J.; Maislin, Greg; Lee, Richard W.W.; Benedikstdsottir, Bryndis; Pack, Allan I.; Gislason, Thorarinn; Juliusson, Sigurdur; Cistulli, Peter A.

2014-01-01

Study Objectives: (1) To determine whether facial phenotype, measured by quantitative photography, relates to underlying craniofacial obstructive sleep apnea (OSA) risk factors, measured with magnetic resonance imaging (MRI); (2) To assess whether these associations are independent of body size and obesity. Design: Cross-sectional cohort. Setting: Landspitali, The National University Hospital, Iceland. Participants: One hundred forty patients (87.1% male) from the Icelandic Sleep Apnea Cohort who had both calibrated frontal and profile craniofacial photographs and upper airway MRI. Mean ± standard deviation age 56.1 ± 10.4 y, body mass index 33.5 ± 5.05 kg/m2, with on-average severe OSA (apnea-hypopnea index 45.4 ± 19.7 h-1). Interventions: N/A. Measurements and Results: Relationships between surface facial dimensions (photos) and facial bony dimensions and upper airway soft-tissue volumes (MRI) was assessed using canonical correlation analysis. Photo and MRI craniofacial datasets related in four significant canonical correlations, primarily driven by measurements of (1) maxillary-mandibular relationship (r = 0.8, P < 0.0001), (2) lower face height (r = 0.76, P < 0.0001), (3) mandibular length (r = 0.67, P < 0.0001), and (4) tongue volume (r = 0.52, P = 0.01). Correlations 1, 2, and 3 were unchanged when controlled for weight and neck and waist circumference. However, tongue volume was no longer significant, suggesting facial dimensions relate to tongue volume as a result of obesity. Conclusions: Significant associations were found between craniofacial variable sets from facial photography and MRI. This study confirms that facial photographic phenotype reflects underlying aspects of craniofacial skeletal abnormalities associated with OSA. Therefore, facial photographic phenotyping may be a useful tool to assess intermediate phenotypes for OSA, particularly in large-scale studies. Citation: Sutherland K, Schwab RJ, Maislin G, Lee RW, Benedikstdsottir B, Pack AI, Gislason T, Juliusson S, Cistulli PA. Facial phenotyping by quantitative photography reflects craniofacial morphology measured on magnetic resonance imaging in icelandic sleep apnea patients. SLEEP 2014;37(5):959-968. PMID:24790275

Ethnicity and skeletal Class III morphology: a pubertal growth analysis using thin-plate spline analysis.

PubMed

Alkhamrah, B; Terada, K; Yamaki, M; Ali, I M; Hanada, K

2001-01-01

A longitudinal retrospective study using thin-plate spline analysis was used to investigate skeletal Class III etiology in Japanese female adolescents. Headfilms of 40 subjects were chosen from the archives of the Orthodontic department at Niigata University Dental Hospital, and were traced at IIIB and IVA Hellman dental ages. Twenty-eight homologous landmarks, representing hard and soft tissue, were digitized. These were used to reproduce a consensus for the profilogram, craniomaxillary complex, mandible, and soft tissue for each age and skeletal group. Generalized least-square analysis revealed a significant shape difference between age-matched groups (P < .001), except for the craniomaxillary complex at stage IVA. T test for size analysis showed unequivocally increased mandibular size in skeletal Class III, which directly increased the craniofacial size collectively (P < .05). A deviant profilogram showed anisotropy displaying as maxillary deficiency, acute cranial base, and obtuse gonial angle in addition to increased facial height at stage IIIB. Maxillary retrusion decreased while the mandible showed excessive incremental growth and a forward position caused by deficient orthocephalization at stage IVA. Craniomaxillary complex total spline and partial warps (PW)3 and 2 showed a maxillary retrusion at stage IIIB opposite an acute cranial base at stage IVA. Mandibular total spline and PW4, 5 showed changes affecting most landmarks and their spatial interrelationship, especially a stretch along the articulare-pogonion axis. In soft tissue analysis, PW8 showed large and local changes which paralleled the underlying hard tissue components. Allometry of the mandible and anisotropy of the cranial base, the maxilla, and the mandible asserted the complexity of craniofacial growth and the difficulty of predicting its outcome.

In vivo bone strain and finite-element modeling of the craniofacial haft in catarrhine primates

PubMed Central

Ross, Callum F; Berthaume, Michael A; Dechow, Paul C; Iriarte-Diaz, Jose; Porro, Laura B; Richmond, Brian G; Spencer, Mark; Strait, David

2011-01-01

Hypotheses regarding patterns of stress, strain and deformation in the craniofacial skeleton are central to adaptive explanations for the evolution of primate craniofacial form. The complexity of craniofacial skeletal morphology makes it difficult to evaluate these hypotheses with in vivo bone strain data. In this paper, new in vivo bone strain data from the intraorbital surfaces of the supraorbital torus, postorbital bar and postorbital septum, the anterior surface of the postorbital bar, and the anterior root of the zygoma are combined with published data from the supraorbital region and zygomatic arch to evaluate the validity of a finite-element model (FEM) of a macaque cranium during mastication. The behavior of this model is then used to test hypotheses regarding the overall deformation regime in the craniofacial haft of macaques. This FEM constitutes a hypothesis regarding deformation of the facial skeleton during mastication. A simplified verbal description of the deformation regime in the macaque FEM is as follows. Inferior bending and twisting of the zygomatic arches about a rostrocaudal axis exerts inferolaterally directed tensile forces on the lateral orbital wall, bending the wall and the supraorbital torus in frontal planes and bending and shearing the infraorbital region and anterior zygoma root in frontal planes. Similar deformation regimes also characterize the crania of Homo and Gorilla under in vitro loading conditions and may be shared among extant catarrhines. Relatively high strain magnitudes in the anterior root of the zygoma suggest that the morphology of this region may be important for resisting forces generated during feeding. PMID:21105871

Neural crest apoptosis and the establishment of craniofacial pattern: an honorable death.

PubMed

Graham, A; Koentges, G; Lumsden, A

1996-01-01

During development of the vertebrate head neural crest cells emigrate from the hindbrain and populate the branchial arches, giving rise to distinct skeletal elements and muscle connective tissues in each arch. The production of neural crest from the hindbrain is discontinuous and crest cells destined for different arches, carrying different positional cues, are separated by regions of apoptosis centered on rhombomeres (r) 3 and r5. This cell death program is under the interactive control of the neighboring hindbrain segments. Both r3 and r5 produce large numbers of crest cells when freed from their flanking rhombomere, but when conjoined with their neighbor the cell death program is restored. Two key components of this program are Bmp 4 and msx-2, both of which are expressed in the apoptotic foci of r3 and r5 and which are also regulated by neighbor interactions. Importantly, the addition of recombinant Bmp 4 to isolated cultures of r3 and r5 induces the expression of Bmp 4 and msx-2 and restores the cell death program. This early neural crest segregation is maintained during development and it has profound effects upon the final craniofacial pattern. Even though crest cells from different axial origins will contribute to compound skeletal elements, these distinct populations do not intermingle. Furthermore head muscle connective tissues are exclusively anchored to skeletal domains arising from neural crest from the same axial level. Thus the discontinuous production of neural crest sculpts the crest into nonmixing streams and consequently ensures the fidelity of patterning.

A Biomechanical Analysis Of Craniofacial Form And Function

NASA Astrophysics Data System (ADS)

Oyen, Ordean J.

1989-04-01

In vivo measures of bite force and bone strain obtained in growing African green monkeys (Cercopeithecus aethiops) are being used to study skull biology and geometry. Strain values and distributional patterns seen in association with forceful jaw elevation are inconsistent with conventional explanations linking upper facial morphology with masticatory function and/or using beam models of craniofacial architecture. These results mandate careful use of notions about skeletal geometry based on static analyses that have not been experimentally verified using in vivo procedures.

Further Analysis of the Crouzon Mouse, Effects of the FGFR2C342Y Mutation are Cranial Bone Dependent

PubMed Central

Liu, Jin; Nam, Hwa Kyung; Wang, Estee; Hatch, Nan E.

2013-01-01

Crouzon syndrome is a debilitating congenital disorder involving abnormal craniofacial skeletal development caused by mutations in Fibroblast Growth Factor Receptor-2 (FGFR2). Phenotypic expression in humans exhibits an autosomal dominant pattern that commonly involves premature fusion of the coronal suture (craniosynostosis) and severe midface hypoplasia. To further investigate biologic mechanisms by which the Crouzon syndrome associated FGFR2C342Y mutation leads to abnormal craniofacial skeletal development we created congenic BALB/c FGFR2C342Y/+ mice. Here we show that BALB/c FGFR2C342Y/+ mice have a consistent craniofacial phenotype including partial fusion of the coronal and lambdoid sutures, intersphenoidal synchondrosis and multiple facial bones, with minimal fusion of other craniofacial sutures. This phenotype is similar to the classic and less severe form of Crouzon syndrome that involves significant midface hypoplasia with limited craniosynostosis. Linear and morphometric analyses demonstrate that FGFR2C342Y/+ mice on the BALB/c genetic background differ significantly in form and shape from their wild type littermates, and that in this genetic background the FGFR2C342Y mutation preferentially effects some craniofacial bones and sutures over others. Analysis of cranial bone cells indicates that the FGFR2C342Y mutation promotes aberrant osteoblast differentiation and increased apoptosis that is more severe in frontal than parietal bone cells. Additionally, FGFR2C342Y/+ frontal but not parietal bones exhibit significantly diminished bone volume and density compared to wild type mice. These results confirm that FGFR2-associated craniosynostosis occurs in association with diminished cranial bone tissue and may provide a potential biologic explanation for the clinical finding of phenotype consistency that exists between many Crouzon syndrome patients. PMID:23358860

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

PubMed

Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

Identification of novel craniofacial regulatory domains located far upstream of SOX9 and disrupted in Pierre Robin sequence

PubMed Central

Gordon, Christopher T.; Attanasio, Catia; Bhatia, Shipra; Benko, Sabina; Ansari, Morad; Tan, Tiong Y.; Munnich, Arnold; Pennacchio, Len A.; Abadie, Véronique; Temple, I. Karen; Goldenberg, Alice; van Heyningen, Veronica; Amiel, Jeanne; FitzPatrick, David; Kleinjan, Dirk A.; Visel, Axel; Lyonnet, Stanislas

2015-01-01

Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions and duplications within a ~2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ~1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harbouring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple non-coding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS. PMID:24934569

Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia.

PubMed

Pehlivan, Davut; Karaca, Ender; Aydin, Hatip; Beck, Christine R; Gambin, Tomasz; Muzny, Donna M; Bilge Geckinli, B; Karaman, Ali; Jhangiani, Shalini N; Gibbs, Richard A; Lupski, James R

2014-09-01

Whole-exome sequencing (WES) is a type of disruptive technology that has tremendous influence on human and clinical genetics research. An efficient and cost-effective method, WES is now widely used as a diagnostic tool for identifying the molecular basis of genetic syndromes that are often challenging to diagnose. Here we report a patient with a clinical diagnosis of cerebro-facio-thoracic dysplasia (CFTD; MIM#213980) in whom we identified a homozygous splice-site mutation in the transmembrane and coiled-coil domains 1 (TMCO1) gene using WES. TMCO1 mutations cause craniofacial dysmorphism, skeletal anomalies characterized by multiple malformations of the vertebrae and ribs, and intellectual disability (MIM#614132). A retrospective review revealed that clinical manifestations of both syndromes are very similar and overlap remarkably. We propose that mutations of TMCO1 are not only responsible for craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome but also for CFTD.

Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia

PubMed Central

Pehlivan, Davut; Karaca, Ender; Aydin, Hatip; Beck, Christine R; Gambin, Tomasz; Muzny, Donna M; Bilge Geckinli, B; Karaman, Ali; Jhangiani, Shalini N; Gibbs, Richard A; Lupski, James R

2014-01-01

Whole-exome sequencing (WES) is a type of disruptive technology that has tremendous influence on human and clinical genetics research. An efficient and cost-effective method, WES is now widely used as a diagnostic tool for identifying the molecular basis of genetic syndromes that are often challenging to diagnose. Here we report a patient with a clinical diagnosis of cerebro-facio-thoracic dysplasia (CFTD; MIM#213980) in whom we identified a homozygous splice-site mutation in the transmembrane and coiled-coil domains 1 (TMCO1) gene using WES. TMCO1 mutations cause craniofacial dysmorphism, skeletal anomalies characterized by multiple malformations of the vertebrae and ribs, and intellectual disability (MIM#614132). A retrospective review revealed that clinical manifestations of both syndromes are very similar and overlap remarkably. We propose that mutations of TMCO1 are not only responsible for craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome but also for CFTD. PMID:24424126

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

PubMed Central

Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias. PMID:26488291

The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

PubMed

Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

2016-07-15

The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. Copyright © 2016 Elsevier Inc. All rights reserved.

Applications of Computer Technology in Complex Craniofacial Reconstruction.

PubMed

Day, Kristopher M; Gabrick, Kyle S; Sargent, Larry A

2018-03-01

To demonstrate our use of advanced 3-dimensional (3D) computer technology in the analysis, virtual surgical planning (VSP), 3D modeling (3DM), and treatment of complex congenital and acquired craniofacial deformities. We present a series of craniofacial defects treated at a tertiary craniofacial referral center utilizing state-of-the-art 3D computer technology. All patients treated at our center using computer-assisted VSP, prefabricated custom-designed 3DMs, and/or 3D printed custom implants (3DPCI) in the reconstruction of craniofacial defects were included in this analysis. We describe the use of 3D computer technology to precisely analyze, plan, and reconstruct 31 craniofacial deformities/syndromes caused by: Pierre-Robin (7), Treacher Collins (5), Apert's (2), Pfeiffer (2), Crouzon (1) Syndromes, craniosynostosis (6), hemifacial microsomia (2), micrognathia (2), multiple facial clefts (1), and trauma (3). In select cases where the available bone was insufficient for skeletal reconstruction, 3DPCIs were fabricated using 3D printing. We used VSP in 30, 3DMs in all 31, distraction osteogenesis in 16, and 3DPCIs in 13 cases. Utilizing these technologies, the above complex craniofacial defects were corrected without significant complications and with excellent aesthetic results. Modern 3D technology allows the surgeon to better analyze complex craniofacial deformities, precisely plan surgical correction with computer simulation of results, customize osteotomies, plan distractions, and print 3DPCI, as needed. The use of advanced 3D computer technology can be applied safely and potentially improve aesthetic and functional outcomes after complex craniofacial reconstruction. These techniques warrant further study and may be reproducible in various centers of care.

Craniofacial structures' development in prenatal period: An MRI study.

PubMed

Begnoni, G; Serrao, G; Musto, F; Pellegrini, G; Triulzi, F M; Dellavia, C

2018-05-01

The development of skeletal structures (cranial base, upper and lower) and upper airways spaces (oropharyngeal and nasopharyngeal) of the skull has always been an issue of great interest in orthodontics. Foetal MRI images obtained as screening exam during pregnancy can help to understand the development of these structures using a sample cephalometric analysis. A total of 28 MRI images in sagittal section of foetuses from 20th to 32th weeks of gestation were obtained to dispel doubts about the presence of skeletal malformations. Cephalometric measurements were performed on MRI T2-dependent images acquired with a 1.5 T scanner. The Software Osirix 5 permits to study sagittal and vertical dimensions of the skull analysing linear measurements, angles and areas of the skeletal structures. Vertical and sagittal dimension of cranial base, maxilla and mandible grow significantly (P < .01) between the second and third trimester of gestational period as well as nasopharyngeal and oropharyngeal spaces (P < .05). High correlation between the development of anterior cranial base and functional areas devoted to speech and swallow is demonstrated (r: .97). The development of craniofacial structures during foetal period seems to show a close correlation between skeletal features and functional spaces with a peak between the second and third trimester of gestation. MRI images result helpful for the clinician to detect with a sample cephalometric analysis anomalies of skeletal and functional structures during prenatal period. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Creation of three-dimensional craniofacial standards from CBCT images

NASA Astrophysics Data System (ADS)

Subramanyan, Krishna; Palomo, Martin; Hans, Mark

2006-03-01

Low-dose three-dimensional Cone Beam Computed Tomography (CBCT) is becoming increasingly popular in the clinical practice of dental medicine. Two-dimensional Bolton Standards of dentofacial development are routinely used to identify deviations from normal craniofacial anatomy. With the advent of CBCT three dimensional imaging, we propose a set of methods to extend these 2D Bolton Standards to anatomically correct surface based 3D standards to allow analysis of morphometric changes seen in craniofacial complex. To create 3D surface standards, we have implemented series of steps. 1) Converting bi-plane 2D tracings into set of splines 2) Converting the 2D splines curves from bi-plane projection into 3D space curves 3) Creating labeled template of facial and skeletal shapes and 4) Creating 3D average surface Bolton standards. We have used datasets from patients scanned with Hitachi MercuRay CBCT scanner providing high resolution and isotropic CT volume images, digitized Bolton Standards from age 3 to 18 years of lateral and frontal male, female and average tracings and converted them into facial and skeletal 3D space curves. This new 3D standard will help in assessing shape variations due to aging in young population and provide reference to correct facial anomalies in dental medicine.

Life-long protein malnutrition in the rat (Rattus norvegicus) results in altered patterns of craniofacial growth and smaller individuals

PubMed Central

Lobe, Shannon L; Bernstein, Marica C; German, Rebecca Z

2006-01-01

Dietary protein is a limiting factor in mammalian growth, significantly affecting the non-linear trajectories of skeletal growth. Young females may be particularly vulnerable to protein malnutrition if the restriction is not lifted before they become reproductive. With such early malnutrition, limited amino acids would be partitioned between two physiological objectives, successful reproduction vs. continued growth. Thus, the consequences of protein malnutrition could affect more than one generation. However, few studies have quantified these cross-generational effects. Our objective was to test for differences in skeletal growth in a second generation of malnourished rats compared with rats malnourished only post-weaning, the first generation and with controls. In this longitudinal study we modelled the growth of 22 craniofacial measurements with the logistic Gompertz equation, and tested for differences in the equation's parameters among the diet groups. The female offspring of post-weaning malnourished dams did not catch up in size to the first generation or to controls, although certain aspects of their craniofacial skeleton were less affected than others. The second generation's growth trajectories resembled the longer and slower growth of the first malnourished generation. There was a complex interaction between developmental processes and early nutritional environment, which affected variation of adult size. PMID:16761979

A novel osteogenic distraction device for the transversal correction of temporozygomatic hypoplasia.

PubMed

Pagnoni, Mario; Fadda, Maria Teresa; Cascone, Piero; Iannetti, Giorgio

2014-07-01

Hemifacial microsomia (HFM) is a congenital disorder characterized by craniofacial malformation of one or both sides of the lower face. Since these anomalies are associated with soft-tissue deficiencies, corrective surgery is often difficult. Bone grafts have typically been used for augmentation, but distraction osteogenesis now offers an alternative for many craniofacial deficiencies, but there are few if any appropriate distraction devices and surgical procedures for the augmentation of craniofacial transversal dimensions. The aim of this study was to evaluate a technique for guided augmentation of craniofacial transversal dimensions through distraction osteogenesis. We tested the efficacy of a prototype distractor, developed in collaboration with Medartis, using cadavers and demonstrated its application for the correction of the transverse dimension of the temporozygomatic region in a patient with Goldenhar syndrome. CT scans showed a 4-mm transverse augmentation of the bony surface after 9 days and a 10-mm increase after 30 days. Upon removal of the distractor (60 days after the first surgery) CT indicated good bony fusion and a stable result in the transverse plane. Six months after removal of the distractor, 3D computed tomography confirmed the success of the transverse augmentation, as it appeared to be stable and reliable. Distraction osteogenesis, using our device, can be used to correct the transverse dimension of the temporozygomatic region in HFM patients. It should also be considered for the correction of residual postsurgical skeletal deficiency due to surgical relapse or deficient growth, and unsatisfactory skeletal contour. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Nasal dermoid sinus cysts: an unusual presentation, computed tomographic scan findings, and surgical results.

PubMed

Posnick, J C; Bortoluzzi, P; Armstrong, D C

1994-05-01

Midline nasal dermoid cysts are congenital lesions resulting from aberrant embryological development. Accurate diagnosis and effective treatment are essential to avoid craniofacial skeletal deformations, cyst rupture, and infection that could cause cutaneous, ocular, or intracranial complications. We report an unusual case of congenital midline nasal dermoid cysts in which an 18-month-old child presented to a hospital emergency department with periorbital cellulitis. It resulted from multiple midline nasal dermoid cysts involving the nasal, forehead, and both orbital regions but without intracranial extension. The patient was successfully managed with a craniofacial approach.

Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

PubMed

Dantas, F P M; Medeiros, G X; Figueiredo, A P M; Thompson, K; Riet-Correa, F

2014-01-01

This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone fractures as indicators of intentional violence in the eastern Adriatic from the antique to the late medieval period (2nd-16th century AD).

PubMed

Slaus, Mario; Novak, Mario; Bedić, Zeljka; Strinović, Davor

2012-09-01

To test the historically documented hypothesis of a general increase in deliberate violence in the eastern Adriatic from the antique (AN; 2nd-6th c.) through the early medieval (EM; 7th-11th c.) to the late-medieval period (LM; 12th-16th c.), an analysis of the frequency and patterning of bone trauma was conducted in three skeletal series from these time periods. A total of 1,125 adult skeletons-346 from the AN, 313 from the EM, and 466 from the LM series-were analyzed. To differentiate between intentional violence and accidental injuries, data for trauma frequencies were collected for the complete skeleton, individual long bones, and the craniofacial region as well as by type of injury (perimortem vs. antemortem). The results of our analyses show a significant temporal increase in total fracture frequencies when calculated by skeleton as well as of individuals exhibiting one skeletal indicator of deliberate violence (sharp force lesions, craniofacial injuries, "parry" fractures, or perimortem trauma). No significant temporal increases were, however, noted in the frequencies of craniofacial trauma, "parry" fractures, perimortem injuries, or of individuals exhibiting multiple skeletal indicators of intentional violence. Cumulatively, these data suggest that the temporal increase in total fracture frequencies recorded in the eastern Adriatic was caused by a combination of factors that included not only an increase of intentional violence but also a significant change in lifestyle that accompanied the transition from a relatively affluent AN urban lifestyle to a more primitive rural medieval way of life. Copyright © 2012 Wiley Periodicals, Inc.

Genetics and Hearing Loss: A Review of Stickler Syndrome.

ERIC Educational Resources Information Center

Nowak, Catherine Bearce

1998-01-01

Stickler syndrome is an autosomal dominant multisystem disease. The four most affected systems are craniofacial, skeletal, ocular, and auditory. The manifestations of Stickler syndrome vary considerably among affected individuals. Audiologists and speech-language pathologists should be familiar with the characteristics associated with Stickler…

The Ptch1DL mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome associated skeletal defects

PubMed Central

Feng, Weiguo; Choi, Irene; Clouthier, David E.; Niswander, Lee; Williams, Trevor

2013-01-01

Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. Employing an ENU-based screen for recessive mutations affecting craniofacial anatomy we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including defects in development of the limbs, scapula, ribcage, secondary palate, cranial base, and cranial vault. In humans, BCNS is often associated with mutations in the Hedgehog receptor PTCH1 and genetic mapping in DL identified a point mutation at a splice donor site in Ptch1. Using genetic complementation analysis we determined that DL is a hypomorphic allele of Ptch1, leading to increased Hedgehog signaling. Two aberrant transcripts are generated by the mutated Ptch1DL gene, which would be predicted to reduce significantly the levels of functional Patched1 protein. This new Ptch1 allele broadens the mouse genetic reagents available to study the Hedgehog pathway and provides a valuable means to study the underlying skeletal abnormalities in BCNS. In addition, these results strengthen the connection between elevated Hedgehog signaling and craniosynostosis. PMID:23897749

[Normal and pathologic mandible development: practical deductions in maxillo-dento-facial orthopedics].

PubMed

Salagnac, Jean-Michel

2016-09-01

The mandible consists of different segments, each of which possess its own specific characteristics regarding emergence, ossification during growth and pathologies. Orthodontists need to be very familiar with these developmental anomalies if they are to avoid failure in their orthopedic or orthodontic treatments and in order to understand the reasons for the lack of success of "conventional" treatments. Each segment must develop correctly if the mandible is to achieve optimal development and occupy a normal position within the cranio-facial complex. The position of the mandible in the cranio-facial block is also conditioned by its attachment to the base of the skull. Combining a detailed semiologic study and a three-dimensional architectural and structural radiologic analysis of clinical cases, this article investigates the various anomalies affecting the mandibular segments and their impact on the craniofacial structure as a whole. An understanding of these anomalies and this analytical method can enable clinicians to perform early diagnosis, avoid undertaking orthopedic and orthodontic treatments which are likely to fail, understand the reasons for unsuccessful "conventional" treatments, provide an orthopedic-surgical guide and make it possible to inform patients correctly. Anomalies affecting the growth of the mandible and its position on the cranial base and their impact on cranio-facial skeletal balance are clearly revealed by structural and architectural analysis, which pinpoints the different clinical elements in skeletal Class II et III cases. In maxilla-dento-facial orthopedics when confronted with a pathology of mandibular origin, it is essential to carefully study the radiographs of each segment of the mandible, to seek out the minor forms of the anomalies and to calculate the position of the mandible on the cranial base relative to the neighboring structures; the skull, the cervical vertebrae and the maxilla. © EDP Sciences, SFODF, 2016.

Lip line changes in Class III facial asymmetry patients after orthodontic camouflage treatment, one-jaw surgery, and two-jaw surgery: A preliminary study.

PubMed

Lee, Gung-Chol; Yoo, Jo-Kwang; Kim, Seong-Hun; Moon, Cheol-Hyun

2017-03-01

To evaluate the effects of orthodontic camouflage treatment (OCT), one-jaw surgery, and two-jaw surgery on the correction of lip line cant (LLC) and to examine factors affecting the correction of LLC in Class III craniofacial asymmetry patients. A sample of 30 Class III craniofacial asymmetry patients was divided into OCT (n = 10), one-jaw surgery (n = 10), and two-jaw surgery (n = 10) groups such that the pretreatment LLC was similar in each group. Pretreatment and posttreatment cone-beam computed tomography scans were used to measure dental and skeletal parameters and LLC. Pretreatment and posttreatment measurements were compared within groups and between groups. Pearson's correlation tests and multiple regression analyses were performed to investigate factors affecting the amount and rate of LLC correction. The average LLC correction was 1.00° in the one-jaw surgery group, and in the two-jaw surgery group, it was 1.71°. In the OCT group it was -0.04°, which differed statistically significantly from the LLC correction in the other two groups. The amount and rate of LLC correction could be explained by settling of skeletal discrepancies or LLC at pretreatment with goodness of fit percentages of approximately 82% and 41%, respectively. Orthognathic surgery resulted in significant correction of LLC in Class III craniofacial asymmetry patients, while OCT did not.

The Roles of RNA Polymerase I and III Subunits Polr1c and Polr1d in Craniofacial Development and in Zebrafish Models of Treacher Collins Syndrome

PubMed Central

Achilleos, Annita; Neben, Cynthia L.; Merrill, Amy E.; Trainor, Paul A.

2016-01-01

Ribosome biogenesis is a global process required for growth and proliferation of all cells, yet perturbation of ribosome biogenesis during human development often leads to tissue-specific defects termed ribosomopathies. Transcription of the ribosomal RNAs (rRNAs) by RNA polymerases (Pol) I and III, is considered a rate limiting step of ribosome biogenesis and mutations in the genes coding for RNA Pol I and III subunits, POLR1C and POLR1D cause Treacher Collins syndrome, a rare congenital craniofacial disorder. Our understanding of the functions of individual RNA polymerase subunits, however, remains poor. We discovered that polr1c and polr1d are dynamically expressed during zebrafish embryonic development, particularly in craniofacial tissues. Consistent with this pattern of activity, polr1c and polr1d homozygous mutant zebrafish exhibit cartilage hypoplasia and cranioskeletal anomalies characteristic of humans with Treacher Collins syndrome. Mechanistically, we discovered that polr1c and polr1d loss-of-function results in deficient ribosome biogenesis, Tp53-dependent neuroepithelial cell death and a deficiency of migrating neural crest cells, which are the primary progenitors of the craniofacial skeleton. More importantly, we show that genetic inhibition of tp53 can suppress neuroepithelial cell death and ameliorate the skeletal anomalies in polr1c and polr1d mutants, providing a potential avenue to prevent the pathogenesis of Treacher Collins syndrome. Our work therefore has uncovered tissue-specific roles for polr1c and polr1d in rRNA transcription, ribosome biogenesis, and neural crest and craniofacial development during embryogenesis. Furthermore, we have established polr1c and polr1d mutant zebrafish as models of Treacher Collins syndrome together with a unifying mechanism underlying its pathogenesis and possible prevention. PMID:27448281

Craniofacial Anomalies And Biostereometrics

NASA Astrophysics Data System (ADS)

Christiansen, Richard L.

1980-07-01

Man's oral-facial structures are vital for the functions of breathing, mastication, swallowing, vision, and communication. When defective development of these tissues occurs, function becomes impaired and the anatomic features of the afflicted individual will frequently deviate from the norm. This error of form and function will classify the individual as being physically and psychosocially handicapped. The successful habilitation regimen of the handicapped person depends on the accurate analysis of both craniofacial anatomy and physiology of these individuals, as well as psychological implications of the disfigurement. Biostereometrics can contribute to the establishment of operationally valid measures for assessing the severity of the handicapping conditions. The heterogeneous nature of diverse disfigurement suggest that an improved classification of malformations would be beneficial. Three-dimensional analysis may also have significant influence on the accuracy of the diagnosis, and the establishment of a biologically sound treatment plan. Biostereometrics will contribute more fully if the three-dimensional surface analysis can be coordinated with a study of 1) the underlying skeletal structures, and 2) the operational musculature. Increased communication between the stereometric experts and the biological scientists should accelerate the application of this technique to the health problem.

Sf3b4-depleted Xenopus embryos: a model to study the pathogenesis of craniofacial defects in Nager syndrome

PubMed Central

Devotta, Arun; Juraver-Geslin, Hugo; Gonzalez, Jose Antonio; Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

2016-01-01

Mandibulofacial dysostosis (MFD) is a human developmental disorder characterized by defects of the facial bones. It is the second most frequent craniofacial malformation after cleft lip and palate. Nager syndrome combines many features of MFD with a variety of limb defects. Mutations in SF3B4 (splicing factor 3b, subunit 4) gene, which encodes a component of the pre-mRNA spliceosomal complex, were recently identified as a cause for Nager syndrome, accounting for 60% of affected individuals. Nothing is known about the cellular pathogenesis underlying Nager type MFD. Here we describe the first animal model for Nager syndrome, generated by knocking down Sf3b4 function in Xenopus laevis embryos, using morpholino antisense oligonucleotides. Our results indicate that Sf3b4-depleted embryos show reduced expression of the neural crest genes sox10, snail2 and twist at the neural plate border, associated with a broadening of the neural plate. This phenotype can be rescued by injection of wild-type human SF3B4 mRNA but not by mRNAs carrying mutations that cause Nager syndrome. At the tailbud stage, morphant embryos had decreased sox10 and tfap2a expression in the pharyngeal arches, indicative of a reduced number of neural crest cells. Later in development, Sf3b4-depleted tadpoles exhibited hypoplasia of neural crest-derived craniofacial cartilages, phenocopying aspects of the craniofacial skeletal defects seen in Nager syndrome patients. With this animal model we are now poised to gain important insights into the etiology and pathogenesis of Nager type MFD, and to identify the molecular targets of Sf3b4. PMID:26874011

Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development.

PubMed

Maruyama, Takamitsu; Jiang, Ming; Abbott, Alycia; Yu, H-M Ivy; Huang, Qirong; Chrzanowska-Wodnicka, Magdalena; Chen, Emily I; Hsu, Wei

2017-09-01

Recent identification and isolation of suture stem cells capable of long-term self-renewal, clonal expanding, and differentiating demonstrate their essential role in calvarial bone development, homeostasis, and injury repair. These bona fide stem cells express a high level of Axin2 and are able to mediate bone regeneration and repair in a cell autonomous fashion. The importance of Axin2 is further demonstrated by its genetic inactivation in mice causing skeletal deformities resembling craniosynostosis in humans. The fate determination and subsequent differentiation of Axin2+ stem cells are highly orchestrated by a variety of evolutionary conserved signaling pathways including Wnt, FGF, and BMP. These signals are often antagonistic of each other and possess differential effects on osteogenic and chondrogenic cell types. However, the mechanisms underlying the interplay of these signaling transductions remain largely elusive. Here we identify Rap1b acting downstream of Axin2 as a signaling interrogator for FGF and BMP. Genetic analysis reveals that Rap1b is essential for development of craniofacial and body skeletons. Axin2 regulates Rap1b through modulation of canonical BMP signaling. The BMP-mediated activation of Rap1b promotes chondrogenic fate and chondrogenesis. Furthermore, by inhibiting MAPK signaling, Rap1b mediates the antagonizing effect of BMP on FGF to repress osteoblast differentiation. Disruption of Rap1b in mice not only enhances osteoblast differentiation but also impairs chondrocyte differentiation during intramembranous and endochondral ossifications, respectively, leading to severe defects in craniofacial and body skeletons. Our findings reveal a dual role of Rap1b in development of the skeletogenic cell types. Rap1b is critical for balancing the signaling effects of BMP and FGF during skeletal development and disease. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Fibroblast growth factor receptor signaling crosstalk in skeletogenesis.

PubMed

Miraoui, Hichem; Marie, Pierre J

2010-11-02

Fibroblast growth factors (FGFs) play important roles in the control of embryonic and postnatal skeletal development by activating signaling through FGF receptors (FGFRs). Germline gain-of-function mutations in FGFR constitutively activate FGFR signaling, causing chondrocyte and osteoblast dysfunctions that result in skeletal dysplasias. Crosstalk between the FGFR pathway and other signaling cascades controls skeletal precursor cell differentiation. Genetic analyses revealed that the interplay of WNT and FGFR1 determines the fate and differentiation of mesenchymal stem cells during mouse craniofacial skeletogenesis. Additionally, interactions between FGFR signaling and other receptor tyrosine kinase networks, such as those mediated by the epidermal growth factor receptor and platelet-derived growth factor receptor α, were associated with excessive osteoblast differentiation and bone formation in the human skeletal dysplasia called craniosynostosis, which is a disorder of skull development. We review the roles of FGFR signaling and its crosstalk with other pathways in controlling skeletal cell fate and discuss how this crosstalk could be pharmacologically targeted to correct the abnormal cell phenotype in skeletal dysplasias caused by aberrant FGFR signaling.

Osteoglophonic dwarfism in two generations.

PubMed Central

Kelley, R I; Borns, P F; Nichols, D; Zackai, E H

1983-01-01

A father and son, both affected by a skeletal dysplasia with severe craniofacial deformities, are reported and compared to three previously described isolated cases of the same dwarfism. The principal features are craniosynostosis, multiple lucent metaphyseal defects, flattening and anterior beaking of the vertebral bodies, and abnormal dentition. Autosomal dominant inheritance is suggested. Images PMID:6606709

Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder

ERIC Educational Resources Information Center

Günes, Serkan; Ekinci, Özalp; Ekinci, Nuran; Toros, Fevziye

2017-01-01

Deletion or duplication of the short arm of chromosome 9 may lead to a variety of clinical conditions including craniofacial and limb abnormalities, skeletal malformations, mental retardation, and autism spectrum disorder. Here, we present a case report of 5-year-old boy with 9p deletion syndrome and autism spectrum disorder.

WNT5A Mutations in Patients with Autosomal Dominant Robinow Syndrome

PubMed Central

Person, Anthony D.; Beiraghi, Soraya; Sieben, Christine M.; Hermanson, Spencer; Neumann, Ann N.; Robu, Mara E.; Schleiffarth, J. Robert; Billington, Charles J.; van Bokhoven, Hans; Hoogeboom, J.; Mazzeu, Juliana F.; Petryk, Anna; Schimmenti, Lisa A.; Brunner, Han G.; Ekker, Stephen C.; Lohr, Jamie L.

2014-01-01

Robinow syndrome is a skeletal dysplasia with both autosomal dominant and autosomal recessive inheritance patterns. It is characterized by short stature, limb shortening, genital hypoplasia and craniofacial abnormalities. The etiology of dominant Robinow syndrome is unknown, however the phenotypically more severe autosomal recessive form of Robinow syndrome has been associated with mutations in the orphan tyrosine kinase receptor, ROR2, which has recently been identified as a putative WNT5A receptor. Here we show that two different missense mutations in WNT5A, which result in amino acid substitutions of highly conserved cysteines, are associated with autosomal dominant Robinow syndrome. One mutation has been found in all living affected members of the original family described by Meinhard Robinow and another in a second unrelated patient. These missense mutations result in decreased WNT5A activity in functional assays of zebrafish and Xenopus development. This work suggests that a WNT5A/ROR2 signal transduction pathway is important in human craniofacial and skeletal development, and that proper formation and growth of these structures is sensitive to variations in WNT5A function. PMID:19918918

Effects of early activator treatment in patients with class II malocclusion evaluated by thin-plate spline analysis.

PubMed

Lux, C J; Rübel, J; Starke, J; Conradt, C; Stellzig, P A; Komposch, P G

2001-04-01

The aim of the present longitudinal cephalometric study was to evaluate the dentofacial shape changes induced by activator treatment between 9.5 and 11.5 years in male Class II patients. For a rigorous morphometric analysis, a thin-plate spline analysis was performed to assess and visualize dental and skeletal craniofacial changes. Twenty male patients with a skeletal Class II malrelationship and increased overjet who had been treated at the University of Heidelberg with a modified Andresen-Häupl-type activator were compared with a control group of 15 untreated male subjects of the Belfast Growth Study. The shape changes for each group were visualized on thin-plate splines with one spline comprising all 13 landmarks to show all the craniofacial shape changes, including skeletal and dento-alveolar reactions, and a second spline based on 7 landmarks to visualize only the skeletal changes. In the activator group, the grid deformation of the total spline pointed to a strong activator-induced reduction of the overjet that was caused both by a tipping of the incisors and by a moderation of sagittal discrepancies, particularly a slight advancement of the mandible. In contrast with this, in the control group, only slight localized shape changes could be detected. Both in the 7- and 13-landmark configurations, the shape changes between the groups differed significantly at P < .001. In the present study, the morphometric approach of thin-plate spline analysis turned out to be a useful morphometric supplement to conventional cephalometrics because the complex patterns of shape change could be suggestively visualized.

A study of cranial variations based on craniometric indices in a South Indian population.

PubMed

Kanchan, Tanuj; Krishan, Kewal; Gupta, Anadi; Acharya, Jenash

2014-09-01

Human skull has been the most extensively studied bone for establishing the taxonomies at evolutionary levels. Crania are also the most commonly used skeletal elements in population studies because they are known to be more genetically driven and less affected by environmental factors. The craniofacial indices are considered as clinical anthropometric parameters used in the investigation of craniofacial skeletal deformities and brain development. The present research is an attempt to study the cranial indices in the South Indian population. The sample for the study included 118 dry adult crania. All the osteometric measurements were taken using standard anthropometric instruments, and 3 indices, namely, cranial index, orbital index (OI), and index of foreman magnum (FMI), were calculated. Cranial index is calculated as (maximum cranial breadth / maximum cranial length) × 100, OI as (orbital height / orbital breadth) × 100, and FMI as (transverse diameter / anteroposterior diameter) × 100. The crania were further classified based on these indices. The cranial index ranged between 66.67 and 85.71 (mean, 78.57 [SD, 4.11]), the OI ranged between 68.89 and 102.63 (mean, 84.23 [SD, 6.64]), and the FMI ranged between 68.57 and 96.88 (mean, 79.71 [SD, 6.98]). Cranial index did not show any significant correlation with the OI (r = -0.162, P = 0.081) or the FMI (r = -0.045, P = 0.626). A statistically significant correlation was, however, observed between OI and FMI (r = -0.232, P = 0.012). The current study developed population-specific classification of crania using cranial indices. This craniometric baseline data pertaining to the craniofacial indices may be useful in presurgical planning and the postsurgical evaluation. It may also assist the forensic anthropologists in the categorization of human skulls, which may be an important component in identification of highly decomposed dead bodies and skeletal remains. More such studies need to be conducted to understand the effect of environment and genetics on the cranial shapes in different population groups.

Computer vision and soft computing for automatic skull-face overlay in craniofacial superimposition.

PubMed

Campomanes-Álvarez, B Rosario; Ibáñez, O; Navarro, F; Alemán, I; Botella, M; Damas, S; Cordón, O

2014-12-01

Craniofacial superimposition can provide evidence to support that some human skeletal remains belong or not to a missing person. It involves the process of overlaying a skull with a number of ante mortem images of an individual and the analysis of their morphological correspondence. Within the craniofacial superimposition process, the skull-face overlay stage just focuses on achieving the best possible overlay of the skull and a single ante mortem image of the suspect. Although craniofacial superimposition has been in use for over a century, skull-face overlay is still applied by means of a trial-and-error approach without an automatic method. Practitioners finish the process once they consider that a good enough overlay has been attained. Hence, skull-face overlay is a very challenging, subjective, error prone, and time consuming part of the whole process. Though the numerical assessment of the method quality has not been achieved yet, computer vision and soft computing arise as powerful tools to automate it, dramatically reducing the time taken by the expert and obtaining an unbiased overlay result. In this manuscript, we justify and analyze the use of these techniques to properly model the skull-face overlay problem. We also present the automatic technical procedure we have developed using these computational methods and show the four overlays obtained in two craniofacial superimposition cases. This automatic procedure can be thus considered as a tool to aid forensic anthropologists to develop the skull-face overlay, automating and avoiding subjectivity of the most tedious task within craniofacial superimposition. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

IN SITU RT-PCR DETECTION OF CYP1A MRNA IN PHARYNGEAL EPITHELIUM AND CHONDROID CELLS OF CHEMICALLY UNTREATED FISH: INVOLVEMENT IN CRANIOFACIAL SKELETAL DEVELOPMENT? (R827102)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Brain, Craniofacial, and Dental Lesions of a Free-ranging Gray Wolf (Canis lupus) Implicated in a Human Attack in Minnesota, USA.

PubMed

Schwabenlander, Marc; Stepaniuk, Kevin; Carstensen, Michelle; Armién, Aníbal G

2016-01-01

We describe significant brain, craniofacial, and dental lesions in a free-ranging wolf (Canis lupus) involved in a human attack. On postmortem examination, the wolf presented asymmetric atrophy and bone remodeling affecting the mandible, incisive, maxilla, lacrimal, palatine, frontal, and ethmoid bones. There was an asymmetrical skeletal malocclusion and dental abnormalities including rotated, malpositioned, partially erupted teeth, and an odontogenic cyst associated with an unerupted canine tooth. Brain changes were bilateral loss and atrophy of extensive cortex regions including olfactory bulb, peduncles, and tract, and the frontal lobe. We highlight the relevance of a thorough postmortem examination of wildlife to elucidate disease-based abnormal behavior as the reason for human-animal conflict.

Impact of facial form on the relationship between conventional or implant-assisted mandibular dentures and masticatory function.

PubMed

Ochiai, Kent T; Hojo, Satoru; Nakamura, Camille; Ikeda, Hideki; Garrett, Neal R

2011-04-01

It is not clear if the interaction of craniofacial form with type of prosthetic restoration (conventional or implant-assisted) is related to masticatory function in complete denture patients. The purpose of this study was to investigate the relationships among facial form, skeletal class, alveolar residual ridge heights and masticatory function in subjects treated with implant-assisted or conventional mandibular dentures with lateral cephalometric evaluation. Data from a previously reported randomized controlled clinical trial were accessed to compare treatment success rates, functional and perceptual outcomes, dietary intake, and craniofacial relationships between mandibular complete dentures and implant overdentures in edentulous diabetic subjects. Evaluation of the digitized post-insertion lateral cephalometric radiographs provided measures of facial form (mesocephalic "medium", brachycephalic "broad and square", dolichocephalic "vertical and long"), skeletal class (Class I, Class II, Class III), and alveolar ridge height (mm), which were compared to results of standardized masticatory tests as evaluated using MANOVA and REGW post-hoc evaluation (α=.05). Masticatory performance on the preferred side was slightly reduced in the dolichocephalic group, compared to brachycephalic and mesocephalic groups (P=.085). Swallowing threshold performance was significantly less in skeletal Class II subjects compared to Class I (P=.034). Maxillary residual alveolar ridge height was significantly less in the brachycephalic group compared to the dolichocephalic group (P<.001). No differences in mandibular ridge height were seen associated with facial form or skeletal class groups. Facial form may be related to masticatory function with conventional and implant-assisted mandibular dentures, but larger controlled studies are needed to confirm this relationship. Alveolar ridge height is reduced in edentulous subjects with a brachycephalic facial form. Copyright © 2011 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Embryonic development of Python sebae - I: Staging criteria and macroscopic skeletal morphogenesis of the head and limbs.

PubMed

Boughner, Julia C; Buchtová, Marcela; Fu, Katherine; Diewert, Virginia; Hallgrímsson, Benedikt; Richman, Joy M

2007-01-01

This study explores the post-ovipositional craniofacial development of the African Rock Python (Python sebae). We first describe a staging system based on external characteristics and next use whole-mount skeletal staining supplemented with Computed tomography (CT) scanning to examine skeletal development. Our results show that python embryos are in early stages of organogenesis at the time of laying, with separate facial prominences and pharyngeal clefts still visible. Limb buds are also visible. By 11 days (stage 3), the chondrocranium is nearly fully formed; however, few intramembranous bones can be detected. One week later (stage 4), many of the intramembranous upper and lower jaw bones are visible but the calvaria are not present. Skeletal elements in the limbs also begin to form. Between stages 4 (day 18) and 7 (day 44), the complete set of intramembranous bones in the jaws and calvaria develops. Hindlimb development does not progress beyond stage 6 (33 days) and remains rudimentary throughout adult life. In contrast to other reptiles, there are two rows of teeth in the upper jaw. The outer tooth row is attached to the maxillary and premaxillary bones, whereas the inner row is attached to the pterygoid and palatine bones. Erupted teeth can be seen in whole-mount stage 10 specimens and are present in an unerupted, mineralized state at stage 7. Micro-CT analysis reveals that all the young membranous bones can be recognized even out of the context of the skull. These data demonstrate intrinsic patterning of the intramembranous bones, even though they form without a cartilaginous template. In addition, intramembranous bone morphology is established prior to muscle function, which can influence bone shape through differential force application. After careful staging, we conclude that python skeletal development occurs slowly enough to observe in good detail the early stages of craniofacial skeletogenesis. Thus, reptilian animal models will offer unique opportunities for understanding the early influences that contribute to perinatal bone shape.

Hedgehog signaling mediates adaptive variation in a dynamic functional system in the cichlid feeding apparatus.

PubMed

Hu, Yinan; Albertson, R Craig

2014-06-10

Adaptive variation in the craniofacial skeleton is a key component of resource specialization and habitat divergence in vertebrates, but the proximate genetic mechanisms that underlie complex patterns of craniofacial variation are largely unknown. Here we demonstrate that the Hedgehog (Hh) signaling pathway mediates widespread variation across a complex functional system that affects the kinematics of lower jaw depression--the opercular four-bar linkage apparatus--among Lake Malawi cichlids. By using a combined quantitative trait locus mapping and population genetics approach, we show that allelic variation in the Hh receptor, ptch1, affects the development of distinct bony elements in the head that represent two of three movable links in this functional system. The evolutionarily derived allele is found in species that feed from the water column, and is associated with shifts in anatomy that translate to a four-bar system capable of faster jaw rotation. Alternatively, the ancestral allele is found in species that feed on attached algae, and is associated with the development of a four-bar system that predicts slower jaw movement. Experimental manipulation of the Hh pathway during cichlid development recapitulates functionally salient natural variation in craniofacial geometry. In all, these results significantly extend our understanding of the mechanisms that fine-tune the craniofacial skeletal complex during adaptation to new foraging niches.

PubMed Central

Paolantonio, E.G.; Antonini, G.; Saulle, R.; La Torre, G.; Deli, R.

2016-01-01

SUMMARY The ratio of bad habits, mouth breathing and malocclusion is an important issue in view of prevention and early treatment of disorders of the craniofacial growth. While bad habits can interfere with the position of the teeth and normal pattern of skeletal growth, on the other hand obstruction of the upper airway, resulting in mouth breathing, changes the pattern of craniofacial growth causing malocclusion. Our crosssectional study, carried out on 3017 children using the ROMA index, was developed to verify if there was a significant correlation between bad habits/mouth breathing and malocclusion. The results showed that an increase in the degree of the index increases the prevalence of bad habits and mouth breathing, meaning that these factors are associated with more severe malocclusions. Moreover, we found a significant association of bad habits with increased overjet and openbite, while no association was found with crossbite. Additionally, we found that mouth breathing is closely related to increased overjet, reduced overjet, anterior or posterior crossbite, openbite and displacement of contact points. Therefore, it is necessary to intervene early on these aetiological factors of malocclusion to prevent its development or worsening and, if already developed, correct it by early orthodontic treatment to promote eugnatic skeletal growth. PMID:27958599

Upper Airway Changes after Orthodontic Extraction Treatment in Adults: A Preliminary Study using Cone Beam Computed Tomography

PubMed Central

Zhang, Jingjing; Chen, Gui; Li, Weiran; Xu, Tianmin; Gao, Xuemei

2015-01-01

Objective Whether the orthodontic treatment with premolar extraction and maximum anchorage in adults will lead to a narrowed upper airway remains under debated. The study aims to investigate the airway changes after orthodontic extraction treatment in adult patients with Class II and hyperdivergent skeletal malocclusion. Materials and Methods This retrospective study enrolled 18 adults with Class II and hyperdivergent skeletal malocclusion (5 males and 13 females, 24.1 ± 3.8 years of age, BMI 20.33 ± 1.77 kg/m2). And 18 untreated controls were matched 1:1 with the treated patients for age, sex, BMI, and skeletal pattern. CBCT images before and after treatment were obtained. DOLPHIN 11.7 software was used to reconstruct and measure the airway size, hyoid position, and craniofacial structures. Changes in the airway and craniofacial parameters from pre to post treatment were assessed by Wilcoxon signed rank test. Mann-Whitney U test was used in comparisons of the airway parameters between the treated patients and the untreated controls. Significant level was set at 0.05. Results The upper and lower incisors retracted 7.87 mm and 6.10 mm based on the measurement of U1-VRL and L1-VRL (P < 0.01), while the positions of the upper and lower molars (U6-VRL, and L6-VRL) remained stable. Volume, height, and cross-sectional area of the airway were not significantly changed after treatment, while the sagittal dimensions of SPP-SPPW, U-MPW, PAS, and V-LPW were significantly decreased (P < 0.05), and the morphology of the cross sections passing through SPP-SPPW, U-MPW, PAS, and V-LPW became anteroposteriorly compressed (P <0.001). No significant differences in the airway volume, height, and cross-sectional area were found between the treated patients and untreated controls. Conclusions The airway changes after orthodontic treatment with premolar extraction and maximum anchorage in adults are mainly morphological changes with anteroposterior dimension compressed in airway cross sections, rather than a decrease in size. PMID:26588714

Engineering craniofacial structures: facing the challenge.

PubMed

Zaky, S H; Cancedda, R

2009-12-01

The human innate regenerative ability is known to be limited by the intensity of the insult together with the availability of progenitor cells, which may cause certain irreparable damage. It is only recently that the paradigm of tissue engineering found its way to the treatment of irreversibly affected body structures with the challenge of reconstructing the lost part. In the current review, we underline recent trials that target engineering of human craniofacial structures, mainly bone, cartilage, and teeth. We analyze the applied engineering strategies relative to the selection of cell types to lay down a specific targeted tissue, together with their association with an escorting scaffold for a particular engineered site, and discuss their necessity to be sustained by growth factors. Challenges and expectations for facial skeletal engineering are discussed in the context of future treatment.

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

Tenorio, Jair; Arias, Pedro; Martínez-Glez, Víctor; Santos, Fernando; García-Miñaur, Sixto; Nevado, Julián; Lapunzina, Pablo

2014-09-20

Simpson-Golabi-Behmel syndrome (SGBS) is a rare overgrowth syndrome clinically characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Abnormalities of the skeletal system, heart, central nervous system, kidney, and gastrointestinal tract may also be observed. Intellectual disability, early motor milestones and speech delay are sometimes present; however, there are a considerable number of individuals with normal intelligence.

Computer-assisted midface reconstruction in Treacher Collins syndrome part 1: skeletal reconstruction.

PubMed

Herlin, Christian; Doucet, Jean Charles; Bigorre, Michèle; Khelifa, Hatem Cheikh; Captier, Guillaume

2013-10-01

Treacher Collins syndrome (TCS) is a severe and complex craniofacial malformation affecting the facial skeleton and soft tissues. The palate as well as the external and middle ear are also affected, but his prognosis is mainly related to neonatal airway management. Methods of zygomatico-orbital reconstruction are numerous and currently use primarily autologous bone, lyophilized cartilage, alloplastic implants, or even free flaps. This work developed a reliable "customized" method of zygomatico-orbital bony reconstruction using a generic reference model tailored to each patient. From a standard computed tomography (CT) acquisition, we studied qualitatively and quantitatively the skeleton of four individuals with TCS whose age was between 6 and 20 years. In parallel, we studied 40 controls at the same age to obtain a morphometric database of reference. Surgical simulation was carried out using validated software used in craniofacial surgery. The zygomatic hypoplasia was very important quantitatively and morphologically in all TCS individuals. Orbital involvement was mainly morphological, with volumes comparable to the controls of the same age. The control database was used to create three-dimensional computer models to be used in the manufacture of cutting guides for autologous cranial bone grafts or alloplastic implants perfectly adapted to each patient's morphology. Presurgical simulation was also used to fabricate custom positioning guides permitting a simple and reliable surgical procedure. The use of a virtual database allowed us to design a reliable and reproducible skeletal reconstruction method for this rare and complex syndrome. The use of presurgical simulation tools seem essential in this type of craniofacial malformation to increase the reliability of these uncommon and complex surgical procedures, and to ensure stable results over time. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Postnatal changes in the growth dynamics of the human face revealed from bone modelling patterns.

PubMed

Martinez-Maza, Cayetana; Rosas, Antonio; Nieto-Díaz, Manuel

2013-09-01

Human skull morphology results from complex processes that involve the coordinated growth and interaction of its skeletal components to keep a functional and structural balance. Previous histological works have studied the growth of different craniofacial regions and their relationship to functional spaces in humans up to 14 years old. Nevertheless, how the growth dynamics of the facial skeleton and the mandible are related and how this relationship changes through the late ontogeny remain poorly understood. To approach these two questions, we have compared the bone modelling activities of the craniofacial skeleton from a sample of subadult and adult humans. In this study, we have established for the first time the bone modelling pattern of the face and the mandible from adult humans. Our analyses reveal a patchy distribution of the bone modelling fields (overemphasized by the presence of surface islands with no histological information) reflecting the complex growth dynamics associated to the individual morphology. Subadult and adult specimens show important differences in the bone modelling patterns of the anterior region of the facial skeleton and the posterior region of the mandible. These differences indicate developmental changes in the growth directions of the whole craniofacial complex, from a predominantly downward growth in subadults that turns to a forward growth observed in the adult craniofacial skeleton. We hypothesize that these ontogenetic changes would respond to the physiological and physical requirements to enlarge the oral and nasal cavities once maturation of the brain and the closure of the cranial sutures have taken place during craniofacial development. © 2013 Anatomical Society.

Elastic properties of external cortical bone in the craniofacial skeleton of the rhesus monkey.

PubMed

Wang, Qian; Dechow, Paul C

2006-11-01

Knowledge of elastic properties and of their variation in the cortical bone of the craniofacial skeleton is indispensable for creating accurate finite-element models to explore the biomechanics and adaptation of the skull in primates. In this study, we measured elastic properties of the external cortex of the rhesus monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight cylindrical cortical specimens were removed from each of six craniofacial skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal and transverse ultrasonic velocities were measured on each specimen to allow calculation of the elastic properties in three dimensions, according to equations derived from Newton's second law and Hooke's law. The axes of maximum stiffness were determined by fitting longitudinal velocities measured along the perimeter of each cortical specimen to a sinusoidal function. Results showed significant differences in elastic properties between different functional areas of the rhesus cranium, and that many sites have a consistent orientation of maximum stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull can be modeled as orthotropic in many regions, and as transversely isotropic in some regions, e.g., the supraorbital region. There are differences from human crania, suggesting that structural differences in skeletal form relate to differences in cortical material properties across species. These differences also suggest that we require more comparative data on elastic properties in primate craniofacial skeletons to explore effectively the functional significance of these differences, especially when these differences are elucidated through modeling approaches, such as finite-element modeling. (c) 2006 Wiley-Liss, Inc.

A correlative study of dental age and skeletal maturation.

PubMed

Sachan, Kiran; Sharma, Vijay Prakash; Tandon, Pradeep

2011-01-01

Skeletal age had been assessed by comparison between maturation of hand-wrist with stages of cervical vertebrae or canine calcification stages in past and this had been closely related to craniofacial growth. The importance of pubertal growth spurt in various types of orthodontic therapies is already established. Hence, this study was aimed to evaluate the relationship of skeletal maturity by hand-wrist with cervical vertebral maturation indicators and canine calcification stages. The study consisted of randomly selected 90 children from Lucknow population with 45 males (age range 10-13 years) and 45 females (age range 9-12 years). Lateral Cephalogram, hand-wrist x-ray, and periapical x-rays of maxillary and mandibular right canines were taken. Mean, standard deviation was calculated of different groups. Correlation was made among cervical vertebral maturation, hand wrist maturation, and canine calcification stages at various age groups. There was strong correlation between skeletal maturation indicator and cervical vertebral maturation indicator for both male (0.849) and female (0.932), whereas correlation between skeletal maturation indicator and canine calcification was good for both male and female (0.635, 0.891). It was concluded that cervical vertebral maturation indicator and canine calcification stages can also be used for assessing skeletal maturity.

Sexual dimorphism in America: geometric morphometric analysis of the craniofacial region.

PubMed

Kimmerle, Erin H; Ross, Ann; Slice, Dennis

2008-01-01

One of the four pillars of the anthropological protocol is the estimation of sex. The protocol generally consists of linear metric analysis or visually assessing individual skeletal traits on the skull and pelvis based on an ordinal scale of 1-5, ranging from very masculine to very feminine. The morphologic traits are then some how averaged by the investigator to estimate sex. Some skulls may be misclassified because of apparent morphologic features that appear more or less robust due to size differences among individuals. The question of misclassification may be further exemplified in light of comparisons across populations that may differ not only in cranial robusticity but also in stature and general physique. The purpose of this study is to further examine the effect of size and sex on craniofacial shape among American populations to better understand the allometric foundation of skeletal traits currently used for sex estimation. Three-dimensional coordinates of 16 standard craniofacial landmarks were collected using a Microscribe-3DX digitizer. Data were collected for 118 American White and Black males and females from the W.M. Bass Donated Collection and the Forensic Data Bank. The MANCOVA procedure tested shape differences as a function of sex and size. Sex had a significant influence on shape for both American Whites (F = 2.90; d.f. = 19, 39; p > F = 0.0024) and Blacks (F = 2.81; d.f. = 19, 37; p > F = 0.0035), whereas size did not have a significant influence on shape in either Whites (F = 1.69; d.f. = 19, 39; p > F = 0.08) or Blacks (F = 1.09; d.f. = 19, 37; p > F = 0.40). Therefore, for each sex, individuals of various sizes were statistically the same shape. In other words, while significant differences were present between the size of males and females (males on average were larger), there was no size effect beyond that accounted for by sex differences in size. Moreover, the consistency between American groups is interesting as it suggests that population differences in sexual dimorphism may result more from human variation in size than allometric variation in craniofacial morphology.

Dissection and Flat-mounting of the Threespine Stickleback Branchial Skeleton

PubMed Central

Ellis, Nicholas A.; Miller, Craig T.

2016-01-01

The posterior pharyngeal segments of the vertebrate head give rise to the branchial skeleton, the primary site of food processing in fish. The morphology of the fish branchial skeleton is matched to a species' diet. Threespine stickleback fish (Gasterosteus aculeatus) have emerged as a model system to study the genetic and developmental basis of evolved differences in a variety of traits. Marine populations of sticklebacks have repeatedly colonized countless new freshwater lakes and creeks. Adaptation to the new diet in these freshwater environments likely underlies a series of craniofacial changes that have evolved repeatedly in independently derived freshwater populations. These include three major patterning changes to the branchial skeleton: reductions in the number and length of gill raker bones, increases in pharyngeal tooth number, and increased branchial bone lengths. Here we describe a detailed protocol to dissect and flat-mount the internal branchial skeleton in threespine stickleback fish. Dissection of the entire three-dimensional branchial skeleton and mounting it flat into a largely two-dimensional prep allows for the easy visualization and quantification of branchial skeleton morphology. This dissection method is inexpensive, fast, relatively easy, and applicable to a wide variety of fish species. In sticklebacks, this efficient method allows the quantification of skeletal morphology in genetic crosses to map genomic regions controlling craniofacial patterning. PMID:27213248

Dissection and Flat-mounting of the Threespine Stickleback Branchial Skeleton.

PubMed

Ellis, Nicholas A; Miller, Craig T

2016-05-07

The posterior pharyngeal segments of the vertebrate head give rise to the branchial skeleton, the primary site of food processing in fish. The morphology of the fish branchial skeleton is matched to a species' diet. Threespine stickleback fish (Gasterosteus aculeatus) have emerged as a model system to study the genetic and developmental basis of evolved differences in a variety of traits. Marine populations of sticklebacks have repeatedly colonized countless new freshwater lakes and creeks. Adaptation to the new diet in these freshwater environments likely underlies a series of craniofacial changes that have evolved repeatedly in independently derived freshwater populations. These include three major patterning changes to the branchial skeleton: reductions in the number and length of gill raker bones, increases in pharyngeal tooth number, and increased branchial bone lengths. Here we describe a detailed protocol to dissect and flat-mount the internal branchial skeleton in threespine stickleback fish. Dissection of the entire three-dimensional branchial skeleton and mounting it flat into a largely two-dimensional prep allows for the easy visualization and quantification of branchial skeleton morphology. This dissection method is inexpensive, fast, relatively easy, and applicable to a wide variety of fish species. In sticklebacks, this efficient method allows the quantification of skeletal morphology in genetic crosses to map genomic regions controlling craniofacial patterning.

An integrated genomic approach for the study of mandibular prognathism in the European seabass (Dicentrarchus labrax).

PubMed

Babbucci, Massimiliano; Ferraresso, Serena; Pauletto, Marianna; Franch, Rafaella; Papetti, Chiara; Patarnello, Tomaso; Carnier, Paolo; Bargelloni, Luca

2016-12-08

Skeletal anomalies in farmed fish are a relevant issue affecting animal welfare and health and causing significant economic losses. Here, a high-density genetic map of European seabass for QTL mapping of jaw deformity was constructed and a genome-wide association study (GWAS) was carried out on a total of 298 juveniles, 148 of which belonged to four full-sib families. Out of 298 fish, 107 were affected by mandibular prognathism (MP). Three significant QTLs and two candidate SNPs associated with MP were identified. The two GWAS candidate markers were located on ChrX and Chr17, both in close proximity with the peaks of the two most significant QTLs. Notably, the SNP marker on Chr17 was positioned within the Sobp gene coding region, which plays a pivotal role in craniofacial development. The analysis of differentially expressed genes in jaw-deformed animals highlighted the "nervous system development" as a crucial pathway in MP. In particular, Zic2, a key gene for craniofacial morphogenesis in model species, was significantly down-regulated in MP-affected animals. Gene expression data revealed also a significant down-regulation of Sobp in deformed larvae. Our analyses, integrating transcriptomic and GWA methods, provide evidence for putative mechanisms underlying seabass jaw deformity.

An integrated genomic approach for the study of mandibular prognathism in the European seabass (Dicentrarchus labrax)

PubMed Central

Babbucci, Massimiliano; Ferraresso, Serena; Pauletto, Marianna; Franch, Rafaella; Papetti, Chiara; Patarnello, Tomaso; Carnier, Paolo; Bargelloni, Luca

2016-01-01

Skeletal anomalies in farmed fish are a relevant issue affecting animal welfare and health and causing significant economic losses. Here, a high-density genetic map of European seabass for QTL mapping of jaw deformity was constructed and a genome-wide association study (GWAS) was carried out on a total of 298 juveniles, 148 of which belonged to four full-sib families. Out of 298 fish, 107 were affected by mandibular prognathism (MP). Three significant QTLs and two candidate SNPs associated with MP were identified. The two GWAS candidate markers were located on ChrX and Chr17, both in close proximity with the peaks of the two most significant QTLs. Notably, the SNP marker on Chr17 was positioned within the Sobp gene coding region, which plays a pivotal role in craniofacial development. The analysis of differentially expressed genes in jaw-deformed animals highlighted the “nervous system development” as a crucial pathway in MP. In particular, Zic2, a key gene for craniofacial morphogenesis in model species, was significantly down-regulated in MP-affected animals. Gene expression data revealed also a significant down-regulation of Sobp in deformed larvae. Our analyses, integrating transcriptomic and GWA methods, provide evidence for putative mechanisms underlying seabass jaw deformity. PMID:27929136

Association between oral habits, mouth breathing and malocclusion.

PubMed

Grippaudo, C; Paolantonio, E G; Antonini, G; Saulle, R; La Torre, G; Deli, R

2016-10-01

The ratio of bad habits, mouth breathing and malocclusion is an important issue in view of prevention and early treatment of disorders of the craniofacial growth. While bad habits can interfere with the position of the teeth and normal pattern of skeletal growth, on the other hand obstruction of the upper airway, resulting in mouth breathing, changes the pattern of craniofacial growth causing malocclusion. Our crosssectional study, carried out on 3017 children using the ROMA index, was developed to verify if there was a significant correlation between bad habits/mouth breathing and malocclusion. The results showed that an increase in the degree of the index increases the prevalence of bad habits and mouth breathing, meaning that these factors are associated with more severe malocclusions. Moreover, we found a significant association of bad habits with increased overjet and openbite, while no association was found with crossbite. Additionally, we found that mouth breathing is closely related to increased overjet, reduced overjet, anterior or posterior crossbite, openbite and displacement of contact points. Therefore, it is necessary to intervene early on these aetiological factors of malocclusion to prevent its development or worsening and, if already developed, correct it by early orthodontic treatment to promote eugnatic skeletal growth. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

Dental and craniofacial findings in eight miniature schnauzer dogs affected by myotonia congenita: preliminary results.

PubMed

Gracis, M; Keith, D; Vite, C H

2000-09-01

Myotonia is a clinical sign characterized by the delay of skeletal muscle relaxation following the cessation of a voluntary activity or the termination of an electrical or mechanical stimulus. Recently, Miniature Schnauzers with myotonia congenita associated with defective chloride ion conductance across the skeletal muscle membrane were identified. Congenital myotonia in these dogs appears to follow an autosomal recessive mode of inheritance. Craniofacial and dental findings of eight Miniature Schnauzer dogs with myotonia congenita are described in the present paper. These findings include: delayed dental eruption of both deciduous and permanent dentition: persistent deciduous dentition; unerupted or partially erupted permanent teeth: crowding and rotation of premolar and or incisor teeth: missing teeth: increased interproximal space between the maxillary fourth premolar and first molar teeth: decreased interproximal space between the maxillary canine and lateral incisor teeth: inability to fully close the mouth due to malocclusion: distoclusion: and, decreased mandibular range of motion. A long narrow skull with a flattened zygomatic arch and greater mandibular body curvature were also consistent findings in the affected dogs. The small number of dogs studied prevents conclusive statements about the origin of these abnormalities, however it is interesting that only 1 of 45 unaffected Miniature Schnauzer dogs showed similar traits.

Assessment of the dental and skeletal effects of fan-type rapid maxillary expansion screw and Hyrax screw on craniofacial structures.

PubMed

Gopalakrishnan, Umarevathi; Sridhar, Premkumar

2017-01-01

The purpose of the study was to assess the skeletal and dental effects of fan-type rapid maxillary expansion (RME) appliance and Hyrax RME appliance on the craniofacial structures. The sample of the study included 12 patients with constricted maxillary arches. Acrylic bonded type of attachment was used for both groups. Changes in sagittal, vertical, and transverse relationship were assessed with lateral and frontal cephalograms, respectively. Intercanine and intermolar widths were measured with stone models. Pre- and immediate post-treatment records were statistically analyzed with Wilcoxon signed-rank test. The differences between the groups were evaluated using Mann-Whitney U-test. Since the data pertaining to intercanine width and intermolar width were normally distributed, parametric test of significance (unpaired t -test) was used to compare them. Results showed that Hyrax presented with significantly greater increments for both nasal cavity width and maxillary width when compared to fan-type RME. Both groups had retroclination of incisors. The increase in the intercanine width was almost similar in both groups. Fan-type RME caused only minimal expansion of the intermolar width when compared to the Hyrax. The ratio between the intercanine and intermolar width expansion was nearly 4:1 in the fan-type RME and 0.75:1 in Hyrax.

Thin-plate spline analysis of the effects of face mask treatment in children with maxillary retrognathism.

PubMed

Chang, Jenny Zwei-Chieng; Liu, Pao-Hsin; Chen, Yi-Jane; Yao, Jane Chung-Chen; Chang, Hong-Po; Chang, Chih-Han; Chang, Frank Hsin-Fu

2006-02-01

Face mask therapy is indicated for growing patients who suffer from maxillary retrognathia. Most previous studies used conventional cephalometric analysis to evaluate the effects of face mask treatment. Cephalometric analysis has been shown to be insufficient for complex craniofacial configurations. The purpose of this study was to investigate changes in the craniofacial structure of children with maxillary retrognathism following face mask treatment by means of thin-plate spline analysis. Thirty children with skeletal Class III malocclusions who had been treated with face masks were compared with a group of 30 untreated gender-matched, age-matched, observation period-matched, and craniofacial configuration-matched subjects. Average geometries, scaled to an equivalent size, were generated by means of Procrustes analysis. Thin-plate spline analysis was then performed for localization of the shape changes. Face mask treatment induced a forward displacement of the maxilla, a counterclockwise rotation of the palatal plane, a horizontal compression of the anterior border of the symphysis and the condylar region, and a downward deformation of the menton. The cranial base exhibited a counterclockwise deformation as a whole. We conclude that thin-plate spline analysis is a valuable supplement to conventional cephalometric analysis.

Heritability of mandibular cephalometric variables in twins with completed craniofacial growth.

PubMed

Šidlauskas, Mantas; Šalomskienė, Loreta; Andriuškevičiūtė, Irena; Šidlauskienė, Monika; Labanauskas, Žygimantas; Vasiliauskas, Arūnas; Kupčinskas, Limas; Juzėnas, Simonas; Šidlauskas, Antanas

2016-10-01

To determine genetic and environmental impact on mandibular morphology using lateral cephalometric analysis of twins with completed mandibular growth and deoxyribonucleic acid (DNA) based zygosity determination. The 39 cephalometric variables of 141 same gender adult pair of twins were analysed. Zygosity was determined using 15 specific DNA markers and cervical vertebral maturation method was used to assess completion of the mandibular growth. A genetic analysis was performed using maximum likelihood genetic structural equation modelling (GSEM). The genetic heritability estimates of angular variables describing horizontal mandibular position in relationship to cranial base and maxilla were considerably higher than in those describing vertical position. The mandibular skeletal cephalometric variables also showed high heritability estimates with angular measurements being considerably higher than linear ones. Results of this study indicate that the angular measurements representing mandibular skeletal morphology (mandibular form) have greater genetic determination than the linear measurements (mandibular size). The shape and sagittal position of the mandible is under stronger genetic control, than is its size and vertical relationship to cranial base. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Molecular cloning, expression of rat Msx-1 and Msx-2 during early embryo genesis and roles for mandibular chondrogenesis].

PubMed

Ishiguro, S

1999-03-01

Quail-chick chimera experiments have shown a contribution of carnial neural crest cells to the craniofacial skeletal elements. Moreover, tissue interactions between epithelial-mesenchymal interaction during early facial process development are required for both skeletal differentiation and morphogenesis. In this study, it was observed that Msx homeobox containing genes expressed in the facial process were important molecules of cartilage morphogenesis. Rat cDNAs were isolated and encoded by Msx-1 and -2, and then the expression patterns using in situ hybridization were investigated during early rat face development. These genes were correlatively expressed in the cranial neural crest forming area (E 9.5 dpc) and the facial process (E 12.5 dpc). Antisence inhibition of Msx genes in the E 12.5 mandibular process exhibited the alteration of their gene expression and cartilage patterns. Antisence inhibition of Msx-1 induced lack of the medial portion of cartilage, and antisence inhibition of Msx-2 enhanced chondrogenesis of mandibular process under the organ culture condition. Thus it was concluded that expression of Msx genes during mandibular process development comprises important signals of chondrogenesis.

Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

PubMed

Brancati, Francesco; Castori, Marco; Mingarelli, Rita; Dallapiccola, Bruno

2005-12-15

We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients. 2005 Wiley-Liss, Inc.

Craniofacial structure variations in patients with palatal anomalies and velopharyngeal dysfunction.

PubMed

Nachmani, Ariela; Aizenbud, Dror; Nageris, Ben; Emodi, Omri; Kassem, Firas

2017-02-01

Cephalometric evaluation of craniofacial and craniopharyngeal morphology is important for understanding the factors affecting velopharyngeal dysfunction (VPD) in patients with palatal anomalies. In this study, 366 patients with VPD were retrospectively stratified into cleft lip and palate (CLP), cleft palate (CP), submucous cleft palate (SMCP), occult submucous cleft palate (OSMCP), and non-CP groups. Lateral cephalometrics were used to assess craniofacial, craniopharyngeal, and velopharyngeal anatomy. The average craniofacial morphology in patients with VPD differed significantly according to the type of palatal anomaly. The non-CP and OSMCP groups differed from the CLP, CP, and SMCP groups in nasopharyngeal size and shape as depicted by a larger ANS-Ptm-Ve angle, a smaller S-N-Ba and NBa-PP angles, and a shorter linear value of S-Ar in the non-CP group. The CLP and CP groups had shorter ANS-Ptm, shorter Ptm-P, and smaller SNA and SNB angles. VPD patients with overt clefts have different skeletal and nasopharyngeal shapes compared to non-CP and OSMCP. Velopharyngeal function assessment should include the size and shape of the nasopharyngeal space in addition to the size and the activity of the velum and posterior and lateral walls of the nasopharynx. This should enable a more precise understanding of VPD pathology, and lead to improvements in the posterior pharyngeal flap technique in order to obtain better postoperative speech outcomes after surgical management of velopharyngeal dysfunction. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Total anomalous pulmonary venous connection and a constellation of craniofacial, skeletal, and urogenital anomalies in a newborn and similar features in his 36-year-old father.

PubMed

Pierson, D M; Taboada, E M; Lofland, G K; Begleiter, M L; Smith, G S; Hall, F; Butler, M G

2001-04-01

We report on a newborn male born to non-consanguineous parents with total anomalous pulmonary venous connection (TAPVC) and additional findings of malformed ears, hypertelorism, brachyphalangy in the hands, pterygium of the elbows, knees, and wrists, complex lower limb pre-axial polydactyly, tibial shortening, clubfeet, horseshoe kidney and a micropenis. He had a 46,XY karyotype. His 36-year-old father had similar craniofacial and limb anomalies suggesting an autosomal dominant syndrome with variable expression. Our patients may represent the 3rd and 4th examples of a newly-described syndrome by Baraitser et al. [(1997) Clin Dysmorphol 6:111-121] which is distinguished by malformed ears, complex pre-axial polydactyly and tibial aplasia in the lower limbs, severe brachyphalangy in the hands, and a micropenis.

Regulation of Facial Morphogenesis by Endothelin Signaling: Insights from Mice and Fish

PubMed Central

Clouthier, David E.; Garcia, Elvin; Schilling, Thomas F.

2010-01-01

Craniofacial morphogenesis is accomplished through a complex set of developmental events, most of which are initiated in neural crest cells within the pharyngeal arches. Local patterning cues from the surrounding environment induce gene expression within neural crest cells, leading to formation of a diverse set of skeletal elements. Endothelin-1 (Edn1) is one of the primary signals that establish the identities of neural crest cells within the mandibular portion of the first pharyngeal arch. Signaling through its cognate receptor, the endothelin-A receptor, is critical for patterning the ventral/distal portion of the arch (lower jaw) and also participates with Hox genes in patterning more posterior arches. Edn1/Ednra signaling is highly conserved between mouse and zebrafish, and genetic analyses in these two species have provided complementary insights into the patterning cues responsible for establishing the craniofacial complex as well as the genetic basis of facial birth defect syndromes. PMID:20684004

Craniofacial morphology of orthodontically untreated patients living in Saxony, Germany.

PubMed

Reich, U; Dannhauer, K H

1996-08-01

The subject of this study is an analysis of the possible specific ethnic characteristics of the craniofacial morphology within the Saxon population. For this purpose we analyzed, in a cephalometric cross-sectional study, lateral cephalometric radiographs taken between 1992 and 1994 of 10,047 orthodontically untreated native Saxon patients. The cephalometric analysis used was a synthesis of several classic procedures as applied at Leipzig University. Among the sagittal parameters there was a relatively high prevalence of mandibular retrognathism and skeletal distal jaw relationship. The vertical parameters displayed a relatively good balance between vertical and horizontal growth patterns. With respect to sexual dimorphism, the differences in the angular parameters and in the indices of relationship were only moderate and so almost irrelevant in clinical terms. Among the age-related changes, the focus is on the increase in the degree of prognathism of both jaws and the anterior rotation of the mandible.

Craniofacial imaging informatics and technology development.

PubMed

Vannier, M W

2003-01-01

'Craniofacial imaging informatics' refers to image and related scientific data from the dentomaxillofacial complex, and application of 'informatics techniques' (derived from disciplines such as applied mathematics, computer science and statistics) to understand and organize the information associated with the data. Major trends in information technology determine the progress made in craniofacial imaging and informatics. These trends include industry consolidation, disruptive technologies, Moore's law, electronic atlases and on-line databases. Each of these trends is explained and documented, relative to their influence on craniofacial imaging. Craniofacial imaging is influenced by major trends that affect all medical imaging and related informatics applications. The introduction of cone beam craniofacial computed tomography scanners is an example of a disruptive technology entering the field. An important opportunity lies in the integration of biologic knowledge repositories with craniofacial images. The progress of craniofacial imaging will continue subject to limitations imposed by the underlying technologies, especially imaging informatics. Disruptive technologies will play a major role in the evolution of this field.

Correlation between frontal sinus dimensions and cephalometric indices: A cross-sectional study

PubMed Central

Tehranchi, Azita; Motamedian, Saeed Reza; Saedi, Sara; Kabiri, Sattar; Shidfar, Shireen

2017-01-01

Objective: Growth prediction plays a significant role in accurate diagnosis and treatment planning of orthodontics patients. It was hypothesized that the unique pattern of pneumatization of the frontal sinus as a component of craniofacial structure would influence the skeletal growth pattern and may be used as a growth predictor. Materials and Methods: A total of 144 subjects (78 females and 66 males) with a mean age of 19.26 ± 4.66 years were included in this retrospective study. Posterior-anterior and lateral cephalograms (LCs) were used to measure the frontal sinus dimensions. The skeletal growth pattern and relations of craniofacial structures were analyzed on LC using variables for sagittal and vertical analyses. Correlation between the frontal sinus dimensions and cephalometric indices was assessed by the Pearson's correlation coefficient. Results: The SN-FH and SNA angles had significant associations with frontal sinus dimensions in all enrolled subjects (P < 0.05). In males, the SN-FH, sum of posterior angles, Pal-SN, and Jarabak index were significantly associated with the size of frontal sinus (P < 0.05). In females, the associations of SN-FH and gonial angles with frontal sinus dimensions were significant (P < 0.05). Conclusion: The results show that larger size of frontal sinus was associated with reduced inclination of the anterior cranial base, increased anterior facial height (in males), and increased gonial angle (in females) in the study population. PMID:28435368

Evolution of Class III treatment in orthodontics.

PubMed

Ngan, Peter; Moon, Won

2015-07-01

Angle, Tweed, and Moyers classified Class III malocclusions into 3 types: pseudo, dentoalveolar, and skeletal. Clinicians have been trying to identify the best timing to intercept a Class III malocclusion that develops as early as the deciduous dentition. With microimplants as skeletal anchorage, orthopedic growth modification became more effective, and it also increased the scope of camouflage orthodontic treatment for patients who were not eligible for orthognathic surgery. However, orthodontic treatment combined with orthognathic surgery remains the only option for patients with a severe skeletal Class III malocclusion or a craniofacial anomaly. Distraction osteogenesis can now be performed intraorally at an earlier age. The surgery-first approach can minimize the length of time that the malocclusion needs to worsen before orthognathic surgery. Finally, the use of computed tomography scans for 3-dimensional diagnosis and treatment planning together with advances in imaging technology can improve the accuracy of surgical movements and the esthetic outcomes for these patients. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Juvenile idiopathic arthritis-and now?: a systematic literature review of changes in craniofacial morphology.

PubMed

von Bremen, Julia; Ruf, Sabine

2012-08-01

To conduct a systematic literature review on the impact of juvenile idiopathic arthritis (JIA) on craniofacial morphology. Several electronic databases (PubMed, Medpilot, Web of Science, DIMDI) were systematically searched for studies that were published up to and including May 2011. In addition, a manual search of the orthodontic and rheumatologic literature was conducted, and reference lists of the selected articles were checked for relevant publications. The identified articles were independently assessed by two investigators and selected according to a three-step process (title/abstract/full text). After completion of the selection procedure, 19 articles were identified possessing great heterogeneity. In most of them, no differentiated analysis of the various JIA subtypes was performed, and type-specific analyses according to mandibular joint effects were seldom. Additional factors such as patient age, disease duration, medication, previous orthodontic treatment as well as the inclusion of a control group were also highly inhomogeneous, which made a meta-analysis of the data impossible. Nevertheless, it appears as if JIA patients tend to develop a hyperdivergent vertical jaw base relationship and a skeletal Class II pattern. Due to the heterogeneous patient samples, it is currently not possible to draw a differentiated conclusion on the influence of various types of JIA on craniofacial morphology.

Hard to Swallow: Developmental Biological Insights into Pediatric Dysphagia

PubMed Central

LaMantia, Anthony-Samuel; Moody, Sally A.; Maynard, Thomas M.; Karpinski, Beverly A.; Zohn, Irene E.; Mendelowitz, David; Lee, Norman H.; Popratiloff, Anastas

2015-01-01

Pediatric dysphagia—feeding and swallowing difficulties that begin at birth, last throughout childhood, and continue into maturity—is one of the most common, least understood complications in children with developmental disorders. We argue that a major cause of pediatric dysphagia is altered hindbrain patterning during pre-natal development. Such changes can compromise craniofacial structures including oropharyngeal muscles and skeletal elements as well as motor and sensory circuits necessary for normal feeding and swallowing. Animal models of developmental disorders that include pediatric dysphagia in their phenotypic spectrum can provide mechanistic insight into pathogenesis of feeding and swallowing difficulties. A fairly common human genetic developmental disorder, DiGeorge/22q11.2 Deletion Syndrome (22q11DS) includes a substantial incidence of pediatric dysphagia in its phenotypic spectrum. Infant mice carrying a parallel deletion to 22q11DS patients have feeding and swallowing difficulties. Altered hindbrain patterning, neural crest migration, craniofacial malformations, and changes in cranial nerve growth prefigure these difficulties. Thus, in addition to craniofacial and pharyngeal anomalies that arise independently of altered neural development, pediatric dysphagia may reflect disrupted hindbrain patterning and its impact on neural circuit development critical for feeding and swallowing. The mechanisms that disrupt hindbrain patterning and circuitry may provide a foundation to develop novel therapeutic approaches for improved clinical management of pediatric dysphagia. PMID:26554723

Craniofacial morphology in children with van der Woude syndrome and isolated cleft palate.

PubMed

Heliövaara, Arja; Karhulahti, Rekina; Rautio, Jorma

2015-01-01

To compare cephalometrically 6-year-old children with van der Woude syndrome and cleft palate (VWS) to children with isolated cleft palate alone (CP). A retrospective case-control study. Forty-four children with VWS were compared to 73 children with CP using lateral cephalograms. The mean age of the children with VWS was 6.6 years (range = 5.9-8.2) and that of the children with CP, 6.2 years (range = 5.7-6.7). Palatal closure had been done at a mean age of 1.4 years (range = 0.8-2.2), mostly with the Veau-Wardill-Killner or the Cronin pushback surgical techniques. The data was collected over a 30-year period. Linear and angular measurements were obtained from lateral cephalograms. A Student's t-test was used in the statistical analysis. The craniofacial morphology in children with VWS and CP was similar, but those with VWS had slightly smaller diameters of the lower pharyngeal airway. The maxilla and mandible were well related to each other, although a little retrusive in relation to the cranial base. The soft tissue profile reflected the skeletal relationships, no significant protrusion of the lower lip was noted. Six-year-old children with VWS and CP have similar craniofacial morphology.

MEPE Localization in the Craniofacial Complex and Function in Tooth Dentin Formation.

PubMed

Gullard, Angela; Gluhak-Heinrich, Jelica; Papagerakis, Silvana; Sohn, Philip; Unterbrink, Aaron; Chen, Shuo; MacDougall, Mary

2016-04-01

Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein found in dental and skeletal tissues. Although information regarding the role of MEPE in bone and disorders of phosphate metabolism is emerging, the role of MEPE in dental tissues remains unclear. We performed RNA in situ hybridization and immunohistochemistry analyses to delineate the expression pattern of MEPE during embryonic and postnatal development in craniofacial mineralizing tissues. Mepe RNA expression was seen within teeth from cap through root formation in association with odontoblasts and cellular cementoblasts. More intense expression was seen in the alveolar bone within the osteoblasts and osteocytes. MEPE immunohistochemistry showed biphasic dentin staining in incisors and more intense staining in alveolar bone matrix and in forming cartilage. Analysis of Mepe null mouse molars showed overall mineralized tooth volume and density of enamel and dentin comparable with that of wild-type samples. However, Mepe(-/-) molars exhibited increased thickness of predentin, dentin, and enamel over controls and decreased gene expression of Enam, Bsp, Dmp1, Dspp, and Opnby RT-PCR. In vitro Mepe overexpression in odontoblasts led to significant reductions in Dspp reporter activity. These data suggest MEPE may be instrumental in craniofacial and dental matrix maturation, potentially functioning in the maintenance of non-mineralized matrix. © 2016 The Histochemical Society.

An unusual case of KBG syndrome with unique oral findings

PubMed Central

Hafiz, Abdul; Mufeed, Abdulla; Ismael, Mohamad; Alam, Mheboob

2015-01-01

KBG syndrome is a condition characterised by macrodontia, neurological disturbance, short stature, a distinct cranio-facial appearance, and skeletal anomalies. The authors describe what appears to be the first case of KBG syndrome reported from the Indian subcontinent. Meticulous evaluation of the dental findings helps to identify such cases which may otherwise remain undiagnosed. Further research is warranted to determine the classic and variant presentations of this condition, with follow-up data providing valuable insights into its natural history and long-term prognosis. PMID:26187867

Effectiveness of interceptive treatment of class III malocclusions with skeletal anchorage: A systematic review and meta-analysis.

PubMed

Rodríguez de Guzmán-Barrera, Jorge; Sáez Martínez, Carla; Boronat-Catalá, Montserrat; Montiel-Company, Jose María; Paredes-Gallardo, Vanessa; Gandía-Franco, José Luís; Almerich-Silla, José Manuel; Bellot-Arcís, Carlos

2017-01-01

Recently, new strategies for treating class III malocclusions have appeared. Skeletal anchorage appears to reduce the dentoalveolar effects while maximising the orthopaedic effect in growing patients. The purpose of this systematic review and meta-analysis is to examine the effectiveness of bone anchorage devices for interceptive treatment of skeletal class III malocclusions. Searches were made in the Pubmed, Embase, Scopus and Cochrane databases, as well as in a grey literature database, and were complemented by hand-searching. The criteria for eligibility were: patients who had undergone orthodontic treatment with skeletal anchorage (miniplates and miniscrews). Patients with syndromes or craniofacial deformities or who had undergone maxillofacial surgery were excluded. The following variables were recorded for each article: author, year of publication, type of study, sample size, dropouts, demographic variables, treatment carried out, radiographic study (2D or 3D), follow-up time, and quality of the articles on the Newcastle-Ottawa Scale. The means and confidence intervals of the following variables were employed: Wits, overjet, ANB, SNA and SNB. Initially, 239 articles were identified. After removing the duplicates and applying the selection criteria, 9 were included in the qualitative synthesis and 7 in the quantitative synthesis (meta-analysis). It may be concluded that skeletal anchorage is an effective treatment for improving skeletal Class III malocclusion, but when compared with other traditional treatments such as disjunction and face mask, there is no clear evidence that skeletal anchorage improves the results.

Effectiveness of interceptive treatment of class III malocclusions with skeletal anchorage: A systematic review and meta-analysis

PubMed Central

Rodríguez de Guzmán-Barrera, Jorge; Sáez Martínez, Carla; Boronat-Catalá, Montserrat; Montiel-Company, Jose María; Paredes-Gallardo, Vanessa; Gandía-Franco, José Luís; Almerich-Silla, José Manuel; Bellot-Arcís, Carlos

2017-01-01

Recently, new strategies for treating class III malocclusions have appeared. Skeletal anchorage appears to reduce the dentoalveolar effects while maximising the orthopaedic effect in growing patients. The purpose of this systematic review and meta-analysis is to examine the effectiveness of bone anchorage devices for interceptive treatment of skeletal class III malocclusions. Searches were made in the Pubmed, Embase, Scopus and Cochrane databases, as well as in a grey literature database, and were complemented by hand-searching. The criteria for eligibility were: patients who had undergone orthodontic treatment with skeletal anchorage (miniplates and miniscrews). Patients with syndromes or craniofacial deformities or who had undergone maxillofacial surgery were excluded. The following variables were recorded for each article: author, year of publication, type of study, sample size, dropouts, demographic variables, treatment carried out, radiographic study (2D or 3D), follow-up time, and quality of the articles on the Newcastle-Ottawa Scale. The means and confidence intervals of the following variables were employed: Wits, overjet, ANB, SNA and SNB. Initially, 239 articles were identified. After removing the duplicates and applying the selection criteria, 9 were included in the qualitative synthesis and 7 in the quantitative synthesis (meta-analysis). It may be concluded that skeletal anchorage is an effective treatment for improving skeletal Class III malocclusion, but when compared with other traditional treatments such as disjunction and face mask, there is no clear evidence that skeletal anchorage improves the results. PMID:28328995

Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development.

PubMed

Bonilla-Claudio, Margarita; Wang, Jun; Bai, Yan; Klysik, Elzbieta; Selever, Jennifer; Martin, James F

2012-02-01

We performed an in depth analysis of Bmp4, a critical regulator of development, disease, and evolution, in cranial neural crest (CNC). Conditional Bmp4 overexpression, using a tetracycline-regulated Bmp4 gain-of-function allele, resulted in facial skeletal changes that were most dramatic after an E10.5 Bmp4 induction. Expression profiling uncovered a signature of Bmp4-induced genes (BIG) composed predominantly of transcriptional regulators that control self-renewal, osteoblast differentiation and negative Bmp autoregulation. The complimentary experiment, CNC inactivation of Bmp2, Bmp4 and Bmp7, resulted in complete or partial loss of multiple CNC-derived skeletal elements, revealing a crucial requirement for Bmp signaling in membranous bone and cartilage development. Importantly, the BIG signature was reduced in Bmp loss-of-function mutants, indicating Bmp-regulated target genes are modulated by Bmp dose. Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation. These data support the hypothesis that Bmp signaling regulates craniofacial skeletal development by balancing self-renewal and differentiation pathways in CNC progenitors.

The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development

PubMed Central

Kirchmaier, Bettina C.; Poon, Kar Lai; Schwerte, Thorsten; Huisken, Jan; Winkler, Christoph; Jungblut, Benno; Stainier, Didier Y.; Brand, Thomas

2013-01-01

The Popeye domain containing (Popdc) genes encode a family of transmembrane proteins with an evolutionary conserved Popeye domain. These genes are abundantly expressed in striated muscle tissue, however their function is not well understood. In this study we have investigated the role of the popdc2 gene in zebrafish. Popdc2 transcripts were detected in the embryonic myocardium and transiently in the craniofacial and tail musculature. Morpholino oligonucleotide-mediated knockdown of popdc2 resulted in aberrant development of skeletal muscle and heart. Muscle segments in the trunk were irregularly shaped and craniofacial muscles were severely reduced or even missing. In the heart, pericardial edema was prevalent in the morphants and heart chambers were elongated and looping was abnormal. These pathologies in muscle and heart were alleviated after reducing the morpholino concentration. However the heart still was abnormal displaying cardiac arrhythmia at later stages of development. Optical recordings of cardiac contractility revealed irregular ventricular contractions with a 2:1, or 3:1 atrial/ventricular conduction ratio, which caused a significant reduction in heart frequency. Recordings of calcium transients with high spatiotemporal resolution using a transgenic calcium indicator line (Tg(cmlc2:gCaMP)s878) and SPIM microscopy confirmed the presence of a severe arrhythmia phenotype. Our results identify popdc2 as a gene important for striated muscle differentiation and cardiac morphogenesis. In addition it is required for the development of the cardiac conduction system. PMID:22290329

Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice.

PubMed

Inoue, Shin-Ichi; Takahara, Shingo; Yoshikawa, Takeo; Niihori, Tetsuya; Yanai, Kazuhiko; Matsubara, Yoichi; Aoki, Yoko

2017-12-01

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Introduction of a new removable adjustable intraoral maxillary distraction system for correction of maxillary hypoplasia.

PubMed

Figueroa, Alvaro A; Polley, John W; Figueroa, Alexander L

2009-09-01

Distraction osteogenesis has become a treatment alternative to treat severe craniofacial skeletal dysplasias. A rigid external distraction device has been successfully used to advance the maxilla as well as the maxillary, orbital, and forehead complex (monobloc) in children as young as 2 years, adolescents, and adults. For this severe group of patients, the technique has been found to be simpler and safer than traditional surgical methods. Maxillary and midfacial advancement through distraction has been found to be extremely stable in the patients in whom the technique was used.The authors introduce an intraoral distractor for those patients requiring a moderate maxillary advancement. The advantages of the device include ease of insertion, vector adjustability, reactivation capabilities, and no need for second procedure for its removal.The above approaches have provided predictable and stable results. A detailed description of the device, necessary orthodontic and surgical procedures, case reports, and cephalometric outcomes are presented. The techniques can be applied alone or as an adjunct to traditional orthognathic and craniofacial surgical procedures.

Calvarial cleidocraniodysplasia-like defects with ENU-induced Nell-1 deficiency.

PubMed

Zhang, Xinli; Ting, Kang; Pathmanathan, Dharmini; Ko, Theodore; Chen, Weiwei; Chen, Feng; Lee, Haofu; James, Aaron W; Siu, Ronald K; Shen, Jia; Culiat, Cymbeline T; Soo, Chia

2012-01-01

Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1's role in craniofacial patterning, we characterized defects of the ENU-induced Nell-1-deficient (END) mice, focusing on both intramembranous and endochondral cranial bones. Results showed that calvarial bones of neonatal END mice were reduced in thickness and density, with a phenotype resembling calvarial cleidocraniodysplasia. In addition, a global reduction in osteoblast markers was observed, including reductions in Runx2, alkaline phosphatase, and osteocalcin. Remarkably, detailed analysis of endochondral bones showed dysplasia as well. The chondrocranium in the END mouse showed enrichment for early, proliferating Sox9⁺ chondrocytes, whereas in contrast markers of chondrocytes maturation were reduced. These data suggest that Nell-1 is an important growth factor for regulation of osteochondral differentiation, by regulating both Runx2 and Sox9 expression within the calvarium. In summary, Nell-1 is required for normal craniofacial membranous and endochondral skeletal development.

An Assessment of Correlation between Dermatoglyphic Patterns and Sagittal Skeletal Discrepancies

PubMed Central

Philip, Biju; Madathody, Deepika; Mathew, Manu; Paul, Jose; Dlima, Johnson Prakash

2017-01-01

Introduction Investigators over years have been fascinated by dermatoglyphic patterns which has led to the development of dermatoglyphics as a science with numerous applications in various fields other than being the best and most widely used method for personal identification. Aim To assess the correlation between dermatoglyphic patterns and sagittal skeletal discrepancies. Materials and Methods A total of 180 patients, aged 18-40 years, were selected from those who attended the outpatient clinic of the Deparment of Orthodontics and Dentofacial Orthopedics, Mar Baselios Dental College, Kothamangalam, Kerala, India. The fingerprints of both hands were taken by ink and stamp method after proper hand washing. The patterns of arches, loops and whorls in fingerprints were assessed. The total ridge count was also evaluated. Data was also sent to the fingerprint experts for expert evaluation. The sagittal jaw relation was determined from the patient’s lateral cephalogram. The collected data was then statistically analyzed using Chi-square tests, ANOVA and Post-hoc tests and a Multinomial regression prediction was also done. Results A significant association was observed between the dermatoglyphic pattern exhibited by eight fingers and the sagittal skeletal discrepancies (p<0.05). An increased distribution of whorl pattern was observed in the skeletal Class II with maxillary excess group and skeletal Class II with mandibular deficiency group while an increased distribution of loop pattern was seen in the skeletal Class III with mandibular excess group and skeletal Class III with maxillary deficiency group. Higher mean of total ridge count was also seen in the groups of skeletal Class II with maxillary excess and skeletal Class II with mandibular deficiency. Multinomial regression predicting skeletal pattern with respect to the fingerprint pattern showed that the left thumb impression fits the best model for predicting the skeletal pattern. Conclusion There was a significant association between dermatoglyphic patterns and sagittal skeletal discrepancies. Dermatoglyphics could serve as a cost effective screening tool of these craniofacial problems. PMID:28511506

A Craniomaxillofacial Surgical Assistance Workstation for Enhanced Single-Stage Reconstruction Using Patient-Specific Implants.

PubMed

Murphy, Ryan J; Liacouras, Peter C; Grant, Gerald T; Wolfe, Kevin C; Armand, Mehran; Gordon, Chad R

2016-11-01

Craniomaxillofacial reconstruction with patient-specific, customized craniofacial implants (CCIs) is ideal for skeletal defects involving areas of aesthetic concern-the non-weight-bearing facial skeleton, temporal skull, and/or frontal-forehead region. Results to date are superior to a variety of "off-the-shelf" materials, but require a protocol computed tomography scan and preexisting defect for computer-assisted design/computer-assisted manufacturing of the CCI. The authors developed a craniomaxillofacial surgical assistance workstation to address these challenges and intraoperatively guide CCI modification for an unknown defect size/shape. First, the surgeon designed an oversized CCI based on his/her surgical plan. Intraoperatively, the surgeon resected the bone and digitized the resection using a navigation pointer. Next, a projector displayed the limits of the craniofacial bone defect onto the prefabricated, oversized CCI for the size modification process; the surgeon followed the projected trace to modify the implant. A cadaveric study compared the standard technique (n = 1) to the experimental technique (n = 5) using surgical time and implant fit. The technology reduced the time and effort needed to resize the oversized CCI by an order of magnitude as compared with the standard manual resizing process. Implant fit was consistently better for the computer-assisted case compared with the control by at least 30%, requiring only 5.17 minutes in the computer-assisted cases compared with 35 minutes for the control. This approach demonstrated improvement in surgical time and accuracy of CCI-based craniomaxillofacial reconstruction compared with previously reported methods. The craniomaxillofacial surgical assistance workstation will provide craniofacial surgeons a computer-assisted technology for effective and efficient single-stage reconstruction when exact craniofacial bone defect sizes are unknown.

A review of hedgehog signaling in cranial bone development

PubMed Central

Pan, Angel; Chang, Le; Nguyen, Alan; James, Aaron W.

2013-01-01

During craniofacial development, the Hedgehog (HH) signaling pathway is essential for mesodermal tissue patterning and differentiation. The HH family consists of three protein ligands: Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Desert Hedgehog (DHH), of which two are expressed in the craniofacial complex (IHH and SHH). Dysregulations in HH signaling are well documented to result in a wide range of craniofacial abnormalities, including holoprosencephaly (HPE), hypotelorism, and cleft lip/palate. Furthermore, mutations in HH effectors, co-receptors, and ciliary proteins result in skeletal and craniofacial deformities. Cranial suture morphogenesis is a delicate developmental process that requires control of cell commitment, proliferation and differentiation. This review focuses on both what is known and what remains unknown regarding HH signaling in cranial suture morphogenesis and intramembranous ossification. As demonstrated from murine studies, expression of both SHH and IHH is critical to the formation and fusion of the cranial sutures and calvarial ossification. SHH expression has been observed in the cranial suture mesenchyme and its precise function is not fully defined, although some postulate SHH to delay cranial suture fusion. IHH expression is mainly found on the osteogenic fronts of the calvarial bones, and functions to induce cell proliferation and differentiation. Unfortunately, neonatal lethality of IHH deficient mice precludes a detailed examination of their postnatal calvarial phenotype. In summary, a number of basic questions are yet to be answered regarding domains of expression, developmental role, and functional overlap of HH morphogens in the calvaria. Nevertheless, SHH and IHH ligands are integral to cranial suture development and regulation of calvarial ossification. When HH signaling goes awry, the resultant suite of morphologic abnormalities highlights the important roles of HH signaling in cranial development. PMID:23565096

Unilateral and bilateral dental transpositions in the maxilla-dental and skeletal findings in 63 individuals.

PubMed

Danielsen, J C; Karimian, K; Ciarlantini, R; Melsen, B; Kjær, I

2015-12-01

This was to elucidate dental and skeletal findings in individuals with unilateral and bilateral maxillary dental transpositions. The sample comprised of radiographic materials from 63 individuals with maxillary dental transpositions from the Departments of Odontology at the Universities of Copenhagen and Aarhus and by the Danish municipal orthodontic service. The cases were divided into three groups: unilateral transposition of the canine and first premolar (Type 1U), bilateral transposition of canine and first premolar (Type 1B), and unilateral transposition of canine and lateral incisor (Type 2). The dentitions were analysed regarding agenesis and dental morphological anomalies on panoramic radiographs, and craniofacial aspects were cephalometrically analysed on profile images The results were statistically evaluated. All groups demonstrated increased occurrences of agenesis (Type 1U and Type 1B: 31 agenesis in 15 patients; and Type 2 three agenesis in three patients). Taurodontic root morphology was most dominant in Type 1U. Peg-shaped lateral incisors showed an increased occurrence, though not in Type 1U. Skeletally, Type 1B and Type 1U demonstrated maxillary retrognathia (more pronounced in Type 1B). Type 2 showed a significant posterior inclination of the maxilla. Transpositions of maxillary canines involve dental and skeletal deviations. Dental deviations were predominantly taurodontic root morphology and agenesis. Regarding skeletal deviations, bilateral transpositions of the canines and the first premolars are associated with skeletal changes. Unilateral transpositions are possibly a localised deviation with minor or no skeletal involvements. The results indicate a possible difference in the aetiologies of unilateral and bilateral transpositions.

Whole-Exome Sequencing of Congenital Glaucoma Patients Reveals Hypermorphic Variants in GPATCH3, a New Gene Involved in Ocular and Craniofacial Development

PubMed Central

Ferre-Fernández, Jesús-José; Aroca-Aguilar, José-Daniel; Medina-Trillo, Cristina; Bonet-Fernández, Juan-Manuel; Méndez-Hernández, Carmen-Dora; Morales-Fernández, Laura; Corton, Marta; Cabañero-Valera, María-José; Gut, Marta; Tonda, Raul; Ayuso, Carmen; Coca-Prados, Miguel; García-Feijoo, Julián; Escribano, Julio

2017-01-01

Congenital glaucoma (CG) is a heterogeneous, inherited and severe optical neuropathy that originates from maldevelopment of the anterior segment of the eye. To identify new disease genes, we performed whole-exome sequencing of 26 unrelated CG patients. In one patient we identified two rare, recessive and hypermorphic coding variants in GPATCH3, a gene of unidentified function, and 5% of a second group of 170 unrelated CG patients carried rare variants in this gene. The recombinant GPATCH3 protein activated in vitro the proximal promoter of CXCR4, a gene involved in embryo neural crest cell migration. The GPATCH3 protein was detected in human tissues relevant to glaucoma (e.g., ciliary body). This gene was expressed in the dermis, skeletal muscles, periocular mesenchymal-like cells and corneal endothelium of early zebrafish embryos. Morpholino-mediated knockdown and transient overexpression of gpatch3 led to varying degrees of goniodysgenesis and ocular and craniofacial abnormalities, recapitulating some of the features of zebrafish embryos deficient in the glaucoma-related genes pitx2 and foxc1. In conclusion, our data suggest the existence of high genetic heterogeneity in CG and provide evidence for the role of GPATCH3 in this disease. We also show that GPATCH3 is a new gene involved in ocular and craniofacial development. PMID:28397860

Thin-plate spline analysis of craniofacial morphology in subjects with adenoid or tonsillar hypertrophy.

PubMed

Baroni, Michela; Ballanti, Fabiana; Polimeni, Antonella; Franchi, Lorenzo; Cozza, Paola

2011-04-01

To compare the skeletal features of subjects with adenoid hypertrophy with those of children with tonsillar hypertrophy using thin-plate spline (TPS) analysis. A group of 20 subjects (9 girls and 11 boys; mean age 8.4 ± 0.9 years) with adenoid hypertrophy (AG) was compared with a group of 20 subjects (10 girls and 10 boys; mean age 8.2 ± 1.1 years) with tonsillar hypertrophy (TG). Craniofacial morphology was analyzed on the lateral cephalograms of the subjects in both groups by means of TPS analysis. A cross-sectional comparison was performed on both size and shape differences between the two groups. AG exhibited statistically significant shape and size differences in craniofacial configuration with respect to TG. Subjects with adenoid hypertrophy showed an upward dislocation of the anterior region of the maxilla, a more downward/backward position of the anterior region of the mandibular body and an upward/backward displacement of the condylar region. Conversely, subjects with tonsillar hypertrophy showed a downward dislocation of the anterior region of the maxilla, a more upward/forward position of the anterior region of the mandibular body and a downward/forward displacement of the condylar region. Subjects with adenoid hypertrophy exhibited features suggesting a more retrognathic mandible while subjects with tonsillar hypertrophy showed features suggesting a more prognathic mandible. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Delayed diagnosis of Gorlin syndrome: Learning from mistakes!

PubMed

Ramanathan, Subramaniyan; Kumar, Devendra; Al Heidous, Mahmoud; Palaniappan, Yegu

2015-01-01

Gorlin syndrome (GS) is a rare inherited multisystem disorder with predisposition to basal cell carcinomas and various other neoplasms. Characteristic features include falx calcification, multiple odontogenic keratocysts (OKCs), early onset medulloblastoma, craniofacial and skeletal malformations, cardiac and ovarian fibroma. We present a case of GS in a 9-year-old girl with recurrent dental infections which was overlooked for 8 years. Diagnosis was finally suggested by the incidental detection of multiple OKCs and ovarian fibromas on follow-up magnetic resonance imaging performed for surveillance of previous operated brain tumor.

Skeletal pattern in subjects with temporomandibular joint disorders

PubMed Central

Almăşan, Oana Cristina; Almăşan, Horea Artimoniu; Bran, Simion; Lascu, Liana; Iancu, Mihaela; Băciuţ, Grigore

2013-01-01

Introduction To establish the skeletal pattern in subjects with malocclusions and temporomandibular disorders (TMD); to assess the relationship between craniofacial skeletal structures and TMD in subjects with malocclusions. Material and methods Sixty-four subjects with malocclusions, over 18 years of age, were included in the study. Temporomandibular disorders were clinically assessed according to the Helkimo Anamnestic Index. Subjects underwent a lateral cephalogram. Subjects were grouped according to the sagittal skeletal pattern (ANB angle) into class I, II and III. Parametric Student tests with equal or unequal variations were used (variations were previously tested with Levene test). Results Twenty-four patients with TMD (experimental sample); 40 patients without TMD (control group); interincisal angle was higher in class I and II (p < 0.05) experimental subjects; overjet was larger in experimental subjects; midline shift and Wits appraisal were broader in the experimental group in all three classes. In class III subjects, the SNB angle was higher in the experimental group (p = 0.01). Joint noises followed by reduced mandible mobility, muscular pain and temporomandibular joint (TMJ) pain were the most frequent symptoms in subjects with TMD and malocclusions. Conclusions Temporomandibular joint status is an important factor to consider when planning orthodontic treatment in patients with severe malocclusions; midline shift, large overjet and deep overbite have been associated with signs and symptoms of TMD. PMID:23515361

Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation.

PubMed

Couser, Natario L; Pande, Chetna K; Turcott, Christie M; Spector, Elaine B; Aylsworth, Arthur S; Powell, Cynthia M

2017-04-01

Pathogenic allelic variants in the fibroblast growth factor receptor 3 (FGFR3) gene have been associated with a number of phenotypes including achondroplasia, hypochondroplasia, thanatophoric dysplasia, Crouzon syndrome with acanthosis nigricans (Crouzonodermoskeletal syndrome), and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans). Crouzon syndrome with acanthosis nigricans is caused by the pathogenic variant c.1172C>A (p.Ala391Glu) in the FGFR3 gene. The p.Lys650Thr pathogenic variant in FGFR3 has been linked to acanthosis nigricans without significant craniofacial or skeletal abnormalities. Recently, an infant with achondroplasia and a novel p.Ser348Cys FGFR3 mutation was reported. We describe the clinical history of an 8-year-old child with a skeletal dysplasia in the achondroplasia-hypochondroplasia spectrum, acanthosis nigricans, typical development, and the recently described p.Ser348Cys FGFR3 mutation. © 2017 Wiley Periodicals, Inc.

Correlation of Beta Angle with Antero-Posterior Dysplasia Indicators and FMA: An Institution Based Cephalometric Study.

PubMed

Singh, Gurinder; Verma, Sanjeev; Singh, Devinder Preet; Yadav, Sumit Kumar; Yadav, Achla Bharti

2016-11-01

Beta angle utilizes three skeletal landmarks - point A, point B, and point C (the apparent axis of the condyle). It is formed between A-B line and point A perpendicular to C-B line. Further this angle indicates the severity and the type of skeletal dysplasia in the sagittal dimension and it changes with the growth pattern of the patient. Hence, it is important to study the dependence of beta angle on the growth pattern. The present study was designed to evaluate the correlation of Beta angle with point A-Nasion-point B (ANB) angle, points A and B to palatal plane (App-Bpp), Wit's appraisal and Maxillary-Mandibular plane angle Bisector (MMB) and Frankfort-Mandibular plane Angle (FMA) in Skeletal Class I, Class II and Class III malocclusion groups. Pre-treatment lateral head cephalo-grams of 120 subjects in age group of 15-25 years were obtained. Three skeletal Class I, Class II and Class III malocclusion groups (40 each) were assorted on the basis of ANB, MMB, App-Bpp, Wit's appraisal and FMA. Analysis of variance (ANOVA) and mean differences were calculated to compare the study groups. Bivariate correlations among different parameters of these groups were obtained. Normal values of beta angle in skeletal Class I group, skeletal Class II group and skeletal Class III group was 31.33±3.25, 25.28±4.28 and 40.93±4.55 respectively. Overall beta angle showed a strong correlation with all parameters of anterio-posterior dysplasia indicators except FMA. Beta angle shows weak correlation with FMA and is not affected by growth pattern/jaw rotation. The normal values are in same range irrespective of the differences in craniofacial morphology.

Correlation of Beta Angle with Antero-Posterior Dysplasia Indicators and FMA: An Institution Based Cephalometric Study

PubMed Central

Singh, Gurinder; Verma, Sanjeev; Singh, Devinder Preet; Yadav, Achla Bharti

2016-01-01

Introduction Beta angle utilizes three skeletal landmarks – point A, point B, and point C (the apparent axis of the condyle). It is formed between A-B line and point A perpendicular to C-B line. Further this angle indicates the severity and the type of skeletal dysplasia in the sagittal dimension and it changes with the growth pattern of the patient. Hence, it is important to study the dependence of beta angle on the growth pattern. Aim The present study was designed to evaluate the correlation of Beta angle with point A–Nasion–point B (ANB) angle, points A and B to palatal plane (App-Bpp), Wit’s appraisal and Maxillary-Mandibular plane angle Bisector (MMB) and Frankfort-Mandibular plane Angle (FMA) in Skeletal Class I, Class II and Class III malocclusion groups. Materials and Methods Pre-treatment lateral head cephalo-grams of 120 subjects in age group of 15-25 years were obtained. Three skeletal Class I, Class II and Class III malocclusion groups (40 each) were assorted on the basis of ANB, MMB, App-Bpp, Wit’s appraisal and FMA. Analysis of variance (ANOVA) and mean differences were calculated to compare the study groups. Bivariate correlations among different parameters of these groups were obtained. Results Normal values of beta angle in skeletal Class I group, skeletal Class II group and skeletal Class III group was 31.33±3.25, 25.28±4.28 and 40.93±4.55 respectively. Overall beta angle showed a strong correlation with all parameters of anterio-posterior dysplasia indicators except FMA. Conclusion Beta angle shows weak correlation with FMA and is not affected by growth pattern/jaw rotation. The normal values are in same range irrespective of the differences in craniofacial morphology. PMID:28050509

Imaging of Skeletal Disorders Caused by Fibroblast Growth Factor Receptor Gene Mutations.

PubMed

Sargar, Kiran M; Singh, Achint K; Kao, Simon C

2017-10-01

Fibroblast growth factors and fibroblast growth factor receptors (FGFRs) play important roles in human axial and craniofacial skeletal development. FGFR1, FGFR2, and FGFR3 are crucial for both chondrogenesis and osteogenesis. Mutations in the genes encoding FGFRs, types 1-3, are responsible for various skeletal dysplasias and craniosynostosis syndromes. Many of these disorders are relatively common in the pediatric population, and diagnosis is often challenging. These skeletal disorders can be classified based on which FGFR is affected. Skeletal disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and osteoglophonic dysplasia, and disorders caused by type 2 mutations include Crouzon syndrome (CS), Apert syndrome (AS), and PS. Disorders caused by type 3 mutations include achondroplasia, hypochondroplasia, thanatophoric dysplasia (TD), severe achondroplasia with developmental delay and acanthosis nigricans, Crouzonodermoskeletal syndrome, and Muenke syndrome. Most of these mutations are inherited in an autosomal dominant fashion and are gain-of-function-type mutations. Imaging plays a key role in the evaluation of these skeletal disorders. Knowledge of the characteristic imaging and clinical findings can help confirm the correct diagnosis and guide the appropriate molecular genetic tests. Some characteristics and clinical findings include premature fusion of cranial sutures and deviated broad thumbs and toes in PS; premature fusion of cranial sutures and syndactyly of the hands and feet in AS; craniosynostosis, ocular proptosis, and absence of hand and foot abnormalities in CS; rhizomelic limb shortening, caudal narrowing of the lumbar interpediculate distance, small and square iliac wings, and trident hands in achondroplasia; and micromelia, bowing of the femora, and platyspondyly in TD. © RSNA, 2017.

The study on facial soft tissue thickness using Han population in Xinjiang.

PubMed

Wang, Jierui; Zhao, Xi; Mi, Congbo; Raza, Iqbal

2016-09-01

Facial profile is an important aspect in physical anthropology, forensic science, and cosmetic research. Thus, facial soft tissue measurement technology plays a significant role in facial restoration. A considerable amount of work has investigated facial soft tissue thickness, which significantly varies according to gender, age, and race. However, only few studies have considered the nutritional status of the investigated individuals. Moreover, no sufficient research among Chinese ethnic groups, particularly Xinjiang population in China, is currently available. Hence, the current study investigated the adaptability of facial soft tissue to the underlying hard tissue among young adults of Han population in Xinjiang, China; the analysis was performed on the basis of gender, skeletal class, and body mass index (BMI). Measurements were obtained from the lateral cephalometric radiographs of 256 adults aged 18-26 years old. Differences in soft tissue thickness were observed between genders and among skeletal classes. With regard to gender, significant differences in soft tissue thickness were found at rhinion, glabella, subnasale, stomion, labrale superius, pogonion, and gnathion among different BMI groups. Thus, nutritional status should be considered when reconstructing an individual's facial profile. Results showed that the thinnest and thickest craniofacial soft tissues existed in rhinion and lip regions, respectively. Overall, this research provides valuable data for forensic facial reconstruction and identification of young adults in Xinjiang, China. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

EPHRIN-B1 Mosaicism Drives Cell Segregation in Craniofrontonasal Syndrome hiPSC-Derived Neuroepithelial Cells.

PubMed

Niethamer, Terren K; Larson, Andrew R; O'Neill, Audrey K; Bershteyn, Marina; Hsiao, Edward C; Klein, Ophir D; Pomerantz, Jason H; Bush, Jeffrey O

2017-03-14

Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of human diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into the pathogenesis of congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations in EFNB1 and characterized by craniofacial, skeletal, and neurological anomalies. Heterozygous females are more severely affected than hemizygous males, a phenomenon termed cellular interference that involves mosaicism for EPHRIN-B1 function. Although the mechanistic basis for cellular interference in CFNS has been hypothesized to involve Eph/ephrin-mediated cell segregation, no direct evidence for this has been demonstrated. Here, by generating hiPSCs from CFNS patients, we demonstrate that mosaicism for EPHRIN-B1 expression induced by random X inactivation in heterozygous females results in robust cell segregation in human neuroepithelial cells, thus supplying experimental evidence that Eph/ephrin-mediated cell segregation is relevant to pathogenesis in human CFNS patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Diversity and Complexity in Chromatin Recognition by TFII-I Transcription Factors in Pluripotent Embryonic Stem Cells and Embryonic Tissues

PubMed Central

Makeyev, Aleksandr V.; Enkhmandakh, Badam; Hong, Seung-Hyun; Joshi, Pujan; Shin, Dong-Guk; Bayarsaihan, Dashzeveg

2012-01-01

GTF2I and GTF2IRD1 encode a family of closely related transcription factors TFII-I and BEN critical in embryonic development. Both genes are deleted in Williams-Beuren syndrome, a complex genetic disorder associated with neurocognitive, craniofacial, dental and skeletal abnormalities. Although genome-wide promoter analysis has revealed the existence of multiple TFII-I binding sites in embryonic stem cells (ESCs), there was no correlation between TFII-I occupancy and gene expression. Surprisingly, TFII-I recognizes the promoter sequences enriched for H3K4me3/K27me3 bivalent domain, an epigenetic signature of developmentally important genes. Moreover, we discovered significant differences in the association between TFII-I and BEN with the cis-regulatory elements in ESCs and embryonic craniofacial tissues. Our data indicate that in embryonic tissues BEN, but not the highly homologous TFII-I, is primarily recruited to target gene promoters. We propose a “feed-forward model” of gene regulation to explain the specificity of promoter recognition by TFII-I factors in eukaryotic cells. PMID:22970219

Diversity and complexity in chromatin recognition by TFII-I transcription factors in pluripotent embryonic stem cells and embryonic tissues.

PubMed

Makeyev, Aleksandr V; Enkhmandakh, Badam; Hong, Seung-Hyun; Joshi, Pujan; Shin, Dong-Guk; Bayarsaihan, Dashzeveg

2012-01-01

GTF2I and GTF2IRD1 encode a family of closely related transcription factors TFII-I and BEN critical in embryonic development. Both genes are deleted in Williams-Beuren syndrome, a complex genetic disorder associated with neurocognitive, craniofacial, dental and skeletal abnormalities. Although genome-wide promoter analysis has revealed the existence of multiple TFII-I binding sites in embryonic stem cells (ESCs), there was no correlation between TFII-I occupancy and gene expression. Surprisingly, TFII-I recognizes the promoter sequences enriched for H3K4me3/K27me3 bivalent domain, an epigenetic signature of developmentally important genes. Moreover, we discovered significant differences in the association between TFII-I and BEN with the cis-regulatory elements in ESCs and embryonic craniofacial tissues. Our data indicate that in embryonic tissues BEN, but not the highly homologous TFII-I, is primarily recruited to target gene promoters. We propose a "feed-forward model" of gene regulation to explain the specificity of promoter recognition by TFII-I factors in eukaryotic cells.

Role of RANKL (TNFSF11)-dependent osteopetrosis in the dental phenotype of Msx2 null mutant mice.

PubMed

Castaneda, Beatriz; Simon, Yohann; Ferbus, Didier; Robert, Benoit; Chesneau, Julie; Mueller, Christopher; Berdal, Ariane; Lézot, Frédéric

2013-01-01

The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal development. During postnatal growth, MSX2 is expressed in all cells involved in mineralized tissue formation and plays a role in their differentiation and function. Msx2 null (Msx2 (-/-)) mice display complex craniofacial skeleton abnormalities with bone and tooth defects. A moderate form osteopetrotic phenotype is observed, along with decreased expression of RANKL (TNFSF11), the main osteoclast-differentiating factor. In order to elucidate the role of such an osteopetrosis in the Msx2 (-/-) mouse dental phenotype, a bone resorption rescue was performed by mating Msx2 (-/-) mice with a transgenic mouse line overexpressing Rank (Tnfrsf11a). Msx2 (-/-) Rank(Tg) mice had significant improvement in the molar phenotype, while incisor epithelium defects were exacerbated in the enamel area, with formation of massive osteolytic tumors. Although compensation for RANKL loss of function could have potential as a therapy for osteopetrosis, but in Msx2 (-/-) mice, this approach via RANK overexpression in monocyte-derived lineages, amplified latent epithelial tumor development in the peculiar continuously growing incisor.

Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development.

PubMed

Townley, Anna K; Feng, Yi; Schmidt, Katy; Carter, Deborah A; Porter, Robert; Verkade, Paul; Stephens, David J

2008-09-15

The COPII coat assembles on endoplasmic reticulum membranes to coordinate the collection of secretory cargo with the formation of transport vesicles. During COPII assembly, Sar1 deforms the membrane and recruits the Sec23-Sec24 complex (Sec23/24), which is the primary cargo-binding adaptor for the system, and Sec13-Sec31 (Sec13/31), which provides a structural outer layer for vesicle formation. Here we show that Sec13 depletion results in concomitant loss of Sec31 and juxtanuclear clustering of pre-budding complexes containing Sec23/24 and cargo. Electron microscopy reveals the presence of curved coated profiles on distended endoplasmic reticulum, indicating that Sec13/31 is not required for the generation or maintenance of the curvature. Surprisingly, export of tsO45-G-YFP, a marker of secretory cargo, is unaffected by Sec13/31 depletion; by contrast, secretion of collagen from primary fibroblasts is strongly inhibited. Suppression of Sec13 expression in zebrafish causes defects in proteoglycan deposition and skeletal abnormalities that are grossly similar to the craniofacial abnormalities of crusher mutant zebrafish and patients with cranio-lenticulo-sutural dysplasia. We conclude that efficient coupling of the inner (Sec23/24) and outer (Sec13/31) layers of the COPII coat is required to drive the export of collagen from the endoplasmic reticulum, and that highly efficient COPII assembly is essential for normal craniofacial development during embryogenesis.

Surgical Orthodontic Treatment for Open Bite in Noonan Syndrome Patient: A Case Report.

PubMed

Kawakami, Masayoshi; Yamamoto, Kazuhiko; Shimomura, Tadahiro; Kirita, Tadaaki

2016-03-01

Noonan syndrome, characterized by short stature, facial anomalies, and congenital heart defects, may also be associated with hematopoietic disorders. Craniofacial anomalies in affected patients include hypertelorism and severe open bite associated with masticatory dysfunction. We treated a Noonan syndrome patient with a skeletal open bite. Surgical orthodontic treatment including two-jaw surgery established a good occlusal relationship after correction of severe anemia. Both upper and lower incisors were moved to upright positions, while clockwise rotation of the palatal plane and decreased mandibular plane angle were accomplished. Lower masticatory activity may affect posttreatment occlusion in such cases.

Customized Polymethyl Methacrylate Implants for the Reconstruction of Craniofacial Osseous Defects

PubMed Central

Fernandes da Silva, André Luis; Borba, Alexandre Meireles; Simão, Niverso Rodrigues; Pedro, Fábio Luis Miranda

2014-01-01

Craniofacial defects represent alterations in the anatomy and morphology of the cranial vault and the facial bones that potentially affect an individual's psychological and social well-being. Although a variety of techniques and restorative procedures have been described for the reconstruction of the affected area, polymethyl methacrylate (PMMA), a biocompatible and nondegradable acrylic resin-based implant, is the most widely used alloplastic material for such craniomaxillofacial reconstruction. The aim of this study was to describe a technique for aesthetic and functional preoperative customized reconstruction of craniofacial bone defects from a small series of patients offered by the Brazilian public health system. Three adult male patients attended consultation with chief complaints directly related to their individual craniofacial bone defects. With the aid of multislice computed tomography scans and subsequent fabrication of the three-dimensional craniofacial prototype, custom-made PMMA implants were fabricated preoperatively. Under general anesthesia, with access to the craniofacial defects with a coronal approach, the PMMA implants were adapted and fixated to the facial skeleton with titanium plates and screws. Postoperative evaluation demonstrated uneventful recovery and an excellent aesthetic result. Customized prefabricated PMMA implants manufactured over the rapid prototyping models proved to be effective and feasible. PMID:25093139

Customized polymethyl methacrylate implants for the reconstruction of craniofacial osseous defects.

PubMed

Fernandes da Silva, André Luis; Borba, Alexandre Meireles; Simão, Niverso Rodrigues; Pedro, Fábio Luis Miranda; Borges, Alvaro Henrique; Miloro, Michael

2014-01-01

Craniofacial defects represent alterations in the anatomy and morphology of the cranial vault and the facial bones that potentially affect an individual's psychological and social well-being. Although a variety of techniques and restorative procedures have been described for the reconstruction of the affected area, polymethyl methacrylate (PMMA), a biocompatible and nondegradable acrylic resin-based implant, is the most widely used alloplastic material for such craniomaxillofacial reconstruction. The aim of this study was to describe a technique for aesthetic and functional preoperative customized reconstruction of craniofacial bone defects from a small series of patients offered by the Brazilian public health system. Three adult male patients attended consultation with chief complaints directly related to their individual craniofacial bone defects. With the aid of multislice computed tomography scans and subsequent fabrication of the three-dimensional craniofacial prototype, custom-made PMMA implants were fabricated preoperatively. Under general anesthesia, with access to the craniofacial defects with a coronal approach, the PMMA implants were adapted and fixated to the facial skeleton with titanium plates and screws. Postoperative evaluation demonstrated uneventful recovery and an excellent aesthetic result. Customized prefabricated PMMA implants manufactured over the rapid prototyping models proved to be effective and feasible.

Craniofacial morphology of Homo floresiensis: description, taxonomic affinities, and evolutionary implication.

PubMed

Kaifu, Yousuke; Baba, Hisao; Sutikna, Thomas; Morwood, Michael J; Kubo, Daisuke; Saptomo, E Wahyu; Jatmiko; Awe, Rokhus Due; Djubiantono, Tony

2011-12-01

This paper describes in detail the external morphology of LB1/1, the nearly complete and only known cranium of Homo floresiensis. Comparisons were made with a large sample of early groups of the genus Homo to assess primitive, derived, and unique craniofacial traits of LB1 and discuss its evolution. Principal cranial shape differences between H. floresiensis and Homo sapiens are also explored metrically. The LB1 specimen exhibits a marked reductive trend in its facial skeleton, which is comparable to the H. sapiens condition and is probably associated with reduced masticatory stresses. However, LB1 is craniometrically different from H. sapiens showing an extremely small overall cranial size, and the combination of a primitive low and anteriorly narrow vault shape, a relatively prognathic face, a rounded oval foramen that is greatly separated anteriorly from the carotid canal/jugular foramen, and a unique, tall orbital shape. Whereas the neurocranium of LB1 is as small as that of some Homo habilis specimens, it exhibits laterally expanded parietals, a weak suprameatal crest, a moderately flexed occipital, a marked facial reduction, and many other derived features that characterize post-habilis Homo. Other craniofacial characteristics of LB1 include, for example, a relatively narrow frontal squama with flattened right and left sides, a marked frontal keel, posteriorly divergent temporal lines, a posteriorly flexed anteromedial corner of the mandibular fossa, a bulbous lateral end of the supraorbital torus, and a forward protruding maxillary body with a distinct infraorbital sulcus. LB1 is most similar to early Javanese Homo erectus from Sangiran and Trinil in these and other aspects. We conclude that the craniofacial morphology of LB1 is consistent with the hypothesis that H. floresiensis evolved from early Javanese H. erectus with dramatic island dwarfism. However, further field discoveries of early hominin skeletal remains from Flores and detailed analyses of the finds are needed to understand the evolutionary history of this endemic hominin species. Copyright © 2011 Elsevier Ltd. All rights reserved.

Skeletal response to maxillary protraction with and without maxillary expansion: a finite element study.

PubMed

Gautam, Pawan; Valiathan, Ashima; Adhikari, Raviraj

2009-06-01

The purpose of this finite element study was to evaluate biomechanically 2 treatment modalities-maxillary protraction alone and in combination with maxillary expansion-by comparing the displacement of various craniofacial structures. Two 3-dimensional analytical models were developed from sequential computed tomography scan images taken at 2.5-mm intervals of a dry young skull. AutoCAD software (2004 version, Autodesk, San Rafael, Calif) and ANSYS software (version 10, Belcan Engineering Group, Cincinnati, Ohio) were used. The model consisted of 108,799 solid 10 node 92 elements, 193,633 nodes, and 580,899 degrees of freedom. In the first model, maxillary protraction forces were simulated by applying 1 kg of anterior force 30 degrees downward to the palatal plane. In the second model, a 4-mm midpalatal suture opening and maxillary protraction were simulated. Forward displacement of the nasomaxillary complex with upward and forward rotation was observed with maxillary protraction alone. No rotational tendency was noted when protraction was carried out with 4 mm of transverse expansion. A tendency for anterior maxillary constriction after maxillary protraction was evident. The amounts of displacement in the frontal, vertical, and lateral directions with midpalatal suture opening were greater compared with no opening of the midpalatal suture. The forward and downward displacements of the nasomaxillary complex with maxillary protraction and maxillary expansion more closely approximated the natural growth direction of the maxilla. Displacements of craniofacial structures were more favorable for the treatment of skeletal Class III maxillary retrognathia when maxillary protraction was used with maxillary expansion. Hence, biomechanically, maxillary protraction combined with maxillary expansion appears to be a superior treatment modality for the treatment of maxillary retrognathia than maxillary protraction alone.

Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

PubMed

Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

2016-01-01

Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

Complex networks for data-driven medicine: the case of Class III dentoskeletal disharmony

NASA Astrophysics Data System (ADS)

Scala, A.; Auconi, P.; Scazzocchio, M.; Caldarelli, G.; McNamara, JA; Franchi, L.

2014-11-01

In the last decade, the availability of innovative algorithms derived from complexity theory has inspired the development of highly detailed models in various fields, including physics, biology, ecology, economy, and medicine. Due to the availability of novel and ever more sophisticated diagnostic procedures, all biomedical disciplines face the problem of using the increasing amount of information concerning each patient to improve diagnosis and prevention. In particular, in the discipline of orthodontics the current diagnostic approach based on clinical and radiographic data is problematic due to the complexity of craniofacial features and to the numerous interacting co-dependent skeletal and dentoalveolar components. In this study, we demonstrate the capability of computational methods such as network analysis and module detection to extract organizing principles in 70 patients with excessive mandibular skeletal protrusion with underbite, a condition known in orthodontics as Class III malocclusion. Our results could possibly constitute a template framework for organising the increasing amount of medical data available for patients’ diagnosis.

Crude oil exposures reveal roles for intracellular calcium cycling in haddock craniofacial and cardiac development

PubMed Central

Sørhus, Elin; Incardona, John P.; Karlsen, Ørjan; Linbo, Tiffany; Sørensen, Lisbet; Nordtug, Trond; van der Meeren, Terje; Thorsen, Anders; Thorbjørnsen, Maja; Jentoft, Sissel; Edvardsen, Rolf B.; Meier, Sonnich

2016-01-01

Recent studies have shown that crude oil exposure affects cardiac development in fish by disrupting excitation-contraction (EC) coupling. We previously found that eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets, potentially leading to more profound toxic effects from uptake of polycyclic aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil (0.7–7 μg/L ∑PAH), here we exposed a broader range of developmental stages over both short and prolonged durations. We quantified effects on cardiac function and morphogenesis, characterized novel craniofacial defects, and examined the expression of genes encoding potential targets underlying cardiac and craniofacial defects. Because of oil droplet binding, a 24-hr exposure was sufficient to create severe cardiac and craniofacial abnormalities. The specific nature of the craniofacial abnormalities suggests that crude oil may target common craniofacial and cardiac precursor cells either directly or indirectly by affecting ion channels and intracellular calcium in particular. Furthermore, down-regulation of genes encoding specific components of the EC coupling machinery suggests that crude oil disrupts excitation-transcription coupling or normal feedback regulation of ion channels blocked by PAHs. These data support a unifying hypothesis whereby depletion of intracellular calcium pools by crude oil-derived PAHs disrupts several pathways critical for organogenesis in fish. PMID:27506155

Dental studies of a Finnish skeletal material: a paleopathologic approach.

PubMed

Varrela, J; Varrela, T M

1991-05-01

This paper reviews a series of paleo-pathologic studies made to investigate associations between dietary factors and development of occlusion, periodontal diseases and caries. The findings indicate that the change from hard to soft food, which has taken place during the last few hundred years, influences occlusion, craniofacial structures and oral health in several ways. Comparative studies show that the frequency of malocclusion has increased substantially. In the same time, a number of alterations have taken place in the morphology of the craniofacial skeleton. The results support the hypothesis that masticatory stress is a regulative factor in craniofacial growth and occlusal development. With soft food and low masticatory activity, jaw growth is not adequate for optimal occlusal development. Approximal wear itself, caused by the attritive diet, seems to be only a minor adjustive factor. Because of the occlusal wear, the crown height decreased with age and the teeth continued to erupt. As a result, root surfaces were exposed. This process has been equated with bone loss but the lack of inflammatory changes on the bone surface indicates that the alveolar bone was not affected by periodontal diseases. This suggests that the alveolar height was maintained at a constant level throughout life and no growth nor resorption took normally place at the crest. Only the exposure of the furcations increased the occurrence of periodontitis. The caries frequency was decreased by mechanical cleaning effect of attritive food but increased by exposure of the root surfaces. Furthermore, the oral microflora may have been modified by factors related to the chemical and physical properties of the diet.

A developmental staging series for the African house snake, Boaedon (Lamprophis) fuliginosus.

PubMed

Boback, Scott M; Dichter, Eric K; Mistry, Hemlata L

2012-02-01

Embryonic staging series are important tools in the study of morphological evolution as they establish a common standard for future studies. In this study, we describe the in ovo embryological development of the African house snake (Boaedon fuliginosus), a non-venomous, egg-laying species within the superfamily Elapoidea. We develop our staging series based on external morphology of the embryo including the head, eye, facial prominences, pharyngeal slits, heart, scales, and endolymphatic ducts. An analysis of embryonic growth in length and mass is presented, as well as preliminary data on craniofacial skeletal development. Our results indicate that B. fuliginosus embryos are well into organogenesis but lack well-defined facial prominences at the time of oviposition. Mandibular and maxillary processes extend rostrally within 8 days (stage 3), corresponding to the first appearance of Meckel's cartilages. Overall, the development of the craniofacial skeleton in B. fuliginosus appears similar to that of other snake species with intramembraneous bones (e.g., dentary and compound bones) ossifying before most of the endochondral bones, the first of which to ossify are the quadrate and the otic capsule. Our staging series is the first to describe the post-ovipositional development of a non-venomous elapoid based on external morphology. This species is an extremely tractable captive that can produce large clutches of eggs every 45 days throughout the year. As such, B. fuliginosus should be a good model for evolutionary developmental biologists focusing on the craniofacial skeleton, loss of limbs, generational teeth, and venom delivery systems. Copyright © 2011 Elsevier GmbH. All rights reserved.

Orofacial manifestations of achondroplasia

PubMed Central

Rohilla, Smriti; Kaushik, Atul; Vinod, V.C.; Tanwar, Renu; Kumar, Munish

2012-01-01

Achondroplasia (Online Mendelian Inheritance in Man [OMIM] 100800), is considered as a form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of special interest in the field of dentistry because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control requires special precautions during dental management. The current case report highlights the orofacial manifestations of Achondroplasia in a young pediatric patient, along with the multidisciplinary treatment (including the dental treatment) done for the patient which also might help the general practitioners in better understanding of the condition. PMID:27298609

[A phenotypic description of 26 patients with Ritscher-Schinzel syndrome (cranio-cerebello-cardiac dysplasia or 3C syndrome)].

PubMed

Pira-Paredes, S M; Montoya-Villada, J H; Franco-Restrepo, J L; Moncada-Velez, M; Cornejo, J W

2017-06-01

Ritscher-Schinzel syndrome (also known as cranio-cerebello-cardiac dysplasia or 3C syndrome) is a rare genetic syndrome that is mainly characterised by the association of cardiac and craniofacial anomalies together with others affecting the posterior fossa. We report on 26 patients with Ritscher-Schinzel syndrome at a hospital in Medellin, in the Department of Antioquia, Colombia. Males account for 69% of this cohort. The mean age of the cohort was 30 months, and 42% were under the age of one year at the time of diagnosis. All of them presented ocular disorders, and megalocornea was the most frequent ocular manifestation (69%), whereas low-set ears (80.7%) and septal heart defects (68.7%) were the most common facial and cardiac malformations, respectively. The most frequent malformations of the posterior fossa were megacisterna magna (31.8%) and Dandy-Walker malformation (27%). 84% of the cases had delayed neurodevelopment or intellectual disability. Skeletal manifestations were frequent: the group consisting of camptodactyly, single palmar crease, overlapping fingers, vertical talus and nail hypoplasia were found in hands and feet in 96% of the cases. Ritscher-Schinzel syndrome is a heterogeneous syndrome from the genetic and clinical point of view. These results suggest that the skeletal and ocular abnormalities that were observed can facilitate the phenotypic diagnosis. However, it is necessary to conduct further studies that allow us to gain a deeper knowledge of its prevalence and help identify other genes involved in this syndrome.

A foxy view of human beauty: implications of the farm fox experiment for understanding the origins of structural and experiential aspects of facial attractiveness.

PubMed

Elia, I E

2013-09-01

Within 20 years, experimental selection of quantified "not too aggressive, not too fearful" behavior to human approach was shown in silver foxes (Vulpes vulpes) to produce a neotenic package of traits in adults: ability to seek, induce, and sustain contact (called friendly or rapport behavior); relatively short limbs and foreshortened skull/face; and light pigmentation areas. Earlier sexual maturation, prolonged receptivity, and larger litters were also noted. The increased estradiol supporting these changes was apparently also responsible for faster skeletal maturation, including earlier fusion of the basicranium causing tooth crowding, but also paedomorphic craniofacial proportions that we find attractive in our own and other species. In this paper, these important findings of the farm fox experiment are juxtaposed with insights from social psychology, physical anthropology, and neuroscience about facial beauty and reaction to it. Since many unrelated species show some or all of the neotenic package or domestication profile when they have achieved rapport past the juvenile stage, craniofacial proportions considered attractive are discussed as genetically and hormonally linked to the evolution of rapport--social contact, trust, and cooperation--whether by natural, intuitive, intentional, or mixed paths of selection.

Association between third molar agenesis and craniofacial structure development.

PubMed

Ramiro-Verdugo, Jara; De Vicente-Corominas, Elena; Montiel-Company, José María; Gandía-Franco, José Luís; Bellot-Arcís, Carlos

2015-11-01

The aim of this investigation was to study the relationship between third molar agenesis-including the number of ageneses-and craniofacial structure growth. We reviewed 305 clinical histories of patients treated at the Orthodontics Unit of the Faculty of Medicine and Dentistry at the University of Valencia in Spain. This included radiographic records of optimal quality. Of these, 40 patients who had agenesis of at least 1 third molar were included in the study group. A control group was formed with another 40 patients with all 4 third molars present. For both groups, a further criterion for inclusion was cone-beam computed tomography records. The cephalometric analysis was performed with NemoCeph 3D software (version 11.3.1.38; Nemotec, Madrid, Spain). The only significant differences between the 2 groups were in the total gonial angle and the upper gonial angle (P ≤0.05), both of which were smaller in the study group. Third molar agenesis is associated with a reduction in Jarabak's gonial angle and upper gonial angle, characteristic of patients with a more horizontal or brachyfacial skeletal pattern. No significant differences were found in other measurements. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Role of RANKL (TNFSF11)-Dependent Osteopetrosis in the Dental Phenotype of Msx2 Null Mutant Mice

PubMed Central

Castaneda, Beatriz; Simon, Yohann; Ferbus, Didier; Robert, Benoit; Chesneau, Julie; Mueller, Christopher

2013-01-01

The MSX2 homeoprotein is implicated in all aspects of craniofacial skeletal development. During postnatal growth, MSX2 is expressed in all cells involved in mineralized tissue formation and plays a role in their differentiation and function. Msx2 null (Msx2 −/−) mice display complex craniofacial skeleton abnormalities with bone and tooth defects. A moderate form osteopetrotic phenotype is observed, along with decreased expression of RANKL (TNFSF11), the main osteoclast-differentiating factor. In order to elucidate the role of such an osteopetrosis in the Msx2 −/− mouse dental phenotype, a bone resorption rescue was performed by mating Msx2 −/− mice with a transgenic mouse line overexpressing Rank (Tnfrsf11a). Msx2 −/− RankTg mice had significant improvement in the molar phenotype, while incisor epithelium defects were exacerbated in the enamel area, with formation of massive osteolytic tumors. Although compensation for RANKL loss of function could have potential as a therapy for osteopetrosis, but in Msx2 −/− mice, this approach via RANK overexpression in monocyte-derived lineages, amplified latent epithelial tumor development in the peculiar continuously growing incisor. PMID:24278237

TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome.

PubMed

Lausch, Ekkehart; Hermanns, Pia; Farin, Henner F; Alanay, Yasemin; Unger, Sheila; Nikkel, Sarah; Steinwender, Christoph; Scherer, Gerd; Spranger, Jürgen; Zabel, Bernhard; Kispert, Andreas; Superti-Furga, Andrea

2008-11-01

Members of the evolutionarily conserved T-box family of transcription factors are important players in developmental processes that include mesoderm formation and patterning and organogenesis both in vertebrates and invertebrates. The importance of T-box genes for human development is illustrated by the association between mutations in several of the 17 human family members and congenital errors of morphogenesis that include cardiac, craniofacial, and limb malformations. We identified two unrelated individuals with a complex cranial, cervical, auricular, and skeletal malformation syndrome with scapular and pelvic hypoplasia (Cousin syndrome) that recapitulates the dysmorphic phenotype seen in the Tbx15-deficient mice, droopy ear. Both affected individuals were homozygous for genomic TBX15 mutations that resulted in truncation of the protein and addition of a stretch of missense amino acids. Although the mutant proteins had an intact T-box and were able to bind to their target DNA sequence in vitro, the missense amino acid sequence directed them to early degradation, and cellular levels were markedly reduced. We conclude that Cousin syndrome is caused by TBX15 insufficiency and is thus the human counterpart of the droopy ear mouse.

Treatment of Severe Maxillary Hypoplasia With Combined Orthodontics and Distraction Osteogenesis.

PubMed

Lucchese, Alessandra; Albertini, Paolo; Asperio, Paolo; Manuelli, Maurizio; Gastaldi, Giorgio

2018-01-05

Distraction osteogenesis (DO) is a technique that allows the generation of new bone in a gap between 2 vascularized bone surfaces in response to the application of graduated tensile stress across the bone gap.Distraction osteogenesis has become a routine treatment of choice to correct skeletal deformities and severe bone defects in the craniofacial complex over the past decade. Distraction osteogenesis has been successfully chosen in lengthening the maxilla and the mandible; in the maxilla and recently in the mandible, the jawbones have been distracted and widened transversely to relieve severe anterior dental crowding and transverse discrepancies between the dental arches.Distraction osteogenesis for maxillary advancement started in 1993 and is now widely used, especially in patients with skeletal Class III malocclusion caused by maxillary hypoplasia.The aim of this study was to present the efficiency of combined orthodontic and DO in the severe maxillary hypoplasia.A 35-year-old Italian man presented to our clinical practice with the chief complaint of esthetic and functionally problems because of skeletal Class III malocclusion with anterior crossbite.Considering that the severity of the skeletal discrepancy is remarkable but compensated by the DO potential, the combined orthodontic and DO treatment was considered adequate, like less invasive and equally effective.It was obtained a good alignment with the upper and lower arch dental alveolar maxillary advancement that allowed to correct the sagittal relationships.The patient was satisfied for the treatment results and had considerable improvement in his self-esteem.

Development and refinement of computer-assisted planning and execution system for use in face-jaw-teeth transplantation to improve skeletal and dento-occlusal outcomes.

PubMed

Hashemi, Sepehr; Armand, Mehran; Gordon, Chad R

2016-10-01

To describe the development and refinement of the computer-assisted planning and execution (CAPE) system for use in face-jaw-teeth transplants (FJTTs). Although successful, some maxillofacial transplants result in suboptimal hybrid occlusion and may require subsequent surgical orthognathic revisions. Unfortunately, the use of traditional dental casts and splints pose several compromising shortcomings in the context of FJTT and hybrid occlusion. Computer-assisted surgery may overcome these challenges. Therefore, the use of computer-assisted orthognathic techniques and functional planning may prevent the need for such revisions and improve facial-skeletal outcomes. A comprehensive CAPE system for use in FJTT was developed through a multicenter collaboration and refined using plastic models, live miniature swine surgery, and human cadaver models. The system marries preoperative surgical planning and intraoperative execution by allowing on-table navigation of the donor fragment relative to recipient cranium, and real-time reporting of patient's cephalometric measurements relative to a desired dental-skeletal outcome. FJTTs using live-animal and cadaveric models demonstrate the CAPE system to be accurate in navigation and beneficial in improving hybrid occlusion and other craniofacial outcomes. Future refinement of the CAPE system includes integration of more commonly performed orthognathic/maxillofacial procedures.

The Drivers of Academic Success in Cleft and Craniofacial Centers: A 10-Year Analysis of over 2000 Publications.

PubMed

Plana, Natalie M; Massie, Jonathan P; Stern, Marleigh J; Alperovich, Michael; Runyan, Christopher M; Staffenberg, David A; Koniaris, Leonidas G; Grayson, Barry H; Diaz-Siso, J Rodrigo; Flores, Roberto L

2017-02-01

Cleft and craniofacial centers require significant investment by medical institutions, yet variables contributing to their academic productivity remain unknown. This study characterizes the elements associated with high academic productivity in these centers. The authors analyzed cleft and craniofacial centers accredited by the American Cleft Palate-Craniofacial Association. Variables such as university affiliation; resident training; number of plastic surgery, oral-maxillofacial, and dental faculty; and investment in a craniofacial surgery, craniofacial orthodontics fellowship program, or both, were obtained. Craniofacial and cleft-related research published between July of 2005 and June of 2015 was identified. A stepwise multivariable linear regression analysis was performed to measure outcomes of total publications, summative impact factor, basic science publications, total journals, and National Institutes of Health funding. One hundred sixty centers were identified, comprising 920 active faculty, 34 craniofacial surgery fellowships, and eight craniofacial orthodontic fellowships; 2356 articles were published in 191 journals. Variables most positively associated with a high number of publications were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.608), craniofacial surgery fellowships (β = 0.231), number of plastic surgery faculty (β = 0.213), and university affiliation (β = 0.165). Variables most positively associated with high a number of journals were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.550), university affiliation (β = 0.251), number of plastic surgery faculty (β = 0.230), and craniofacial surgery fellowship (β = 0.218). Variables most positively associated with a high summative impact factor were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.648), craniofacial surgery fellowship (β = 0.208), number of plastic surgery faculty (β = 0.207), and university affiliation (β = 0.116). Variables most positively associated with basic science publications were craniofacial surgery and craniofacial orthodontics fellowships (β = 0.676) and craniofacial surgery fellowship (β = 0.208). The only variable associated with National Institutes of Health funding was craniofacial surgery and craniofacial orthodontics fellowship (β = 0.332). Participation in both craniofacial surgery and orthodontics fellowships demonstrates the strongest association with academic success; craniofacial surgery fellowship, university affiliation, and number of surgeons are also predictive.

Effect of growth hormone treatment on craniofacial growth in children: Idiopathic short stature versus growth hormone deficiency.

PubMed

Choi, Sung-Hwan; Fan, Dong; Hwang, Mi-Soo; Lee, Hee-Kyung; Hwang, Chung-Ju

2017-04-01

Few studies have evaluated craniofacial growth in boys and girls with idiopathic short stature (ISS) during growth hormone (GH) treatment. The aim of this study was to evaluate the effect of GH treatment on craniofacial growth in children with ISS, compared with those with growth hormone deficiency (GHD). This study included 36 children (mean age, 11.3 ± 1.8 years) who were treated with GH consecutively. Lateral cephalograms were analyzed before and 2 years after start of GH treatment. There were no significant differences in age and sex between ISS and GHD groups and the reference group from semilongitudinal study (10 boys and 8 girls from each group). Before treatment, girls with ISS showed a skeletal Class II facial profile compared with the GHD and reference groups (p = 0.003). During GH treatment, the amount of maxillary length increased beyond norm in the ISS and GHD groups in boys (p = 0.035) > 3 standard deviation score (SDS). Meanwhile, mandibular ramus height (p = 0.001), corpus length, and total mandibular length (p = 0.007 for both) increased more in girls with ISS than in girls with GHD. Lower and total anterior facial heights increased more in girls with ISS than in girls with GHD (p = 0.021 and p = 0.007, respectively), > 7-11 SDS. GH should be administered carefully when treating girls with ISS, because GH treatment has great effects on vertical overgrowth of the mandible and can result in longer face. Copyright © 2016. Published by Elsevier B.V.

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: population affinities and pathological abnormalities.

PubMed

Jacob, T; Indriati, E; Soejono, R P; Hsü, K; Frayer, D W; Eckhardt, R B; Kuperavage, A J; Thorne, A; Henneberg, M

2006-09-05

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose that LB1 is drawn from an earlier pygmy H. sapiens population but individually shows signs of a developmental abnormality, including microcephaly. Additional mandibular and postcranial remains from the site share small body size but not microcephaly.

Facial skeletal augmentation using hydroxyapatite cement.

PubMed

Shindo, M L; Costantino, P D; Friedman, C D; Chow, L C

1993-02-01

This study investigates the use of a new calcium phosphate cement, which sets to solid, microporous hydroxyapatite, for facial bone augmentation. In six dogs, the supraorbital ridges were augmented bilaterally with this hydroxyapatite cement. On one side, the hydroxyapatite cement was placed directly onto the bone within a subperiosteal pocket. On the opposite side, the cement was contained within a collagen membrane tubule and then inserted into a subperiosteal pocket. The use of collagen tubules facilitated easy, precise placement of the cement. All implants maintained their original augmented height throughout the duration of the study. They were well tolerated without extrusion or migration, and there was no significant sustained inflammatory response. Histologic studies, performed at 3, 6, and 9 months revealed that when the cement was placed directly onto bone, progressive replacement of the implant by bone (osseointegration of the hydroxyapatite with the underlying bone) without a loss of volume was observed. In contrast, when the cement-collagen tubule combination was inserted, primarily a fibrous union was noted. Despite such fibrous union, the hydroxyapatite-collagen implant solidly bonded to the underlying bone, and no implant resorption was observed. Hydroxyapatite cement can be used successfully for the experimental augmentation of the craniofacial skeleton and may be applicable for such uses in humans.

Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.

PubMed

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L; Baserga, Susan; Yelick, Pamela C

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

Orthodontic and surgical management of a patient with severe skeletal Class II deformity and facial asymmetry: A case report with a 5-year follow-up.

PubMed

Gao, Xiang; Wang, Tao; Song, Jinlin

2017-04-01

In this case report, we present the orthodontic and surgical management of an 18-year-old girl who had a severe craniofacial deformity, including maxillary prognathism, vertical maxillary excess (gummy smile), mandibular retrognathism, receding chin, and facial asymmetry caused by unilateral temporomandibular joint ankylosis. For correction of the facial asymmetry, the patient's right mandibular ramus and body were lengthened via distraction osteogenesis after 5 months of preoperative orthodontic therapy. Subsequently, extraction of 4 first premolars, bimaxillary anterior segmental osteotomy, and genioplasty were simultaneously performed in the second-stage operation to correct the skeletal deformities in the sagittal and vertical planes. Postoperative orthodontic treatment completed the final occlusal adjustment. The total active treatment period lasted approximately 30 months. The clinical results show that the patient's facial esthetics were significantly improved with minimal surgical invasion and distress, and a desirable occlusion was achieved. These pleasing results were maintained during the 5-year follow-up. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Using Zebrafish to Test the Genetic Basis of Human Craniofacial Diseases.

PubMed

Machado, R Grecco; Eames, B Frank

2017-10-01

Genome-wide association studies (GWASs) opened an innovative and productive avenue to investigate the molecular basis of human craniofacial disease. However, GWASs identify candidate genes only; they do not prove that any particular one is the functional villain underlying disease or just an unlucky genomic bystander. Genetic manipulation of animal models is the best approach to reveal which genetic loci identified from human GWASs are functionally related to specific diseases. The purpose of this review is to discuss the potential of zebrafish to resolve which candidate genetic loci are mechanistic drivers of craniofacial diseases. Many anatomic, embryonic, and genetic features of craniofacial development are conserved among zebrafish and mammals, making zebrafish a good model of craniofacial diseases. Also, the ability to manipulate gene function in zebrafish was greatly expanded over the past 20 y, enabling systems such as Gateway Tol2 and CRISPR-Cas9 to test gain- and loss-of-function alleles identified from human GWASs in coding and noncoding regions of DNA. With the optimization of genetic editing methods, large numbers of candidate genes can be efficiently interrogated. Finding the functional villains that underlie diseases will permit new treatments and prevention strategies and will increase understanding of how gene pathways operate during normal development.

Sleep-Disordered Breathing in Children with Rare Skeletal Disorders: A Survey of Clinical Records.

PubMed

Zaffanello, Marco; Piacentini, Giorgio; Sacchetto, Luca; Pietrobelli, Angelo; Gasperi, Emma; Barillari, Marco; Cardobi, Nicolò; Nosetti, Luana; Ramaroli, Diego; Antoniazzi, Franco

2018-06-21

Craniofacial disharmony in skeletal diseases is strongly associated with sleep-disordered breathing. Our aim was to study sleep respiratory patterns in young children with rare skeletal disorders. This retrospective study included children with achondroplasia, osteogenesis imperfecta and Ellis van Creveld Syndrome. Our subjects underwent an in-laboratory overnight respiratory polygraph between January 2012 and April 2016. All medical records were reviewed and brain Magnetic Resonance Imaging was conducted on patients with achondroplasia, nasopharynx, oropharynx and laryngopharynx spaces. 24 children were enrolled, 13 with Achondroplasia, 2 with spondyloepiphyseal dysplasia, 1 with odontochondrodysplasia, 6 with osteogenesis imperfecta and 2 with Ellis van Creveld Syndrome. Children with achondroplasia, who had adenotonsillectomy, showed fewer sleep respiratory involvement than untreated children. Among 13 patients with Achondroplasia, brain magnetic resonance imaging was available in 10 subjects and significant negative correlation was found between sleep respiratory patterns, nasopharynx and oropharynx space (p < 0.05). In 2 patients with spondyloepiphyseal dysplasia, mild to moderate sleep respiratory involvement was found. Both subjects had history of adenotonsillectomy. Mild sleep respiratory involvement was also shown in 4 out of 6 patients with osteogenesis imperfecta. One patient with Ellis van Creveld syndrome had mild sleep respiratory disturbance. Sleep respiratory disturbances were detected in children with achondroplasia, and with less severity also in osteogenesis imperfecta and Ellis van Creveld syndrome. Adenotonsillectomy was successful in achondroplasia in reducing symptoms. In light of our findings, multicenter studies are needed to obtain further information on these rare skeletal diseases. ©2018The Author(s). Published by S. Karger AG, Basel.

Bilateral cleft lip and palate: A morphometric analysis of facial skeletal form using cone beam computed tomography.

PubMed

Starbuck, John M; Ghoneima, Ahmed; Kula, Katherine

2015-07-01

Bilateral cleft lip and palate (BCLP) is caused by a lack of merging of maxillary and nasal facial prominences during development and morphogenesis. BCLP is associated with congenital defects of the oronasal facial region that can impair ingestion, mastication, speech, and dentofacial development. Using cone beam computed tomography (CBCT) images, 7- to 18-year old individuals born with BCLP (n = 15) and age- and sex-matched controls (n = 15) were retrospectively assessed. Coordinate values of three-dimensional facial skeletal anatomical landmarks (n = 32) were measured from each CBCT image. Data were evaluated using principal coordinates analysis (PCOORD) and Euclidean Distance Matrix Analysis (EDMA). PCOORD axes 1-3 explain approximately 45% of the morphological variation between samples, and specific patterns of morphological differences were associated with each axis. Approximately, 30% of facial skeletal measures significantly differ by confidence interval testing (α = 0.10) between samples. While significant form differences occur across the facial skeleton, strong patterns of differences are localized to the lateral and superioinferior aspects of the nasal aperture. In conclusion, the BCLP deformity significantly alters facial skeletal morphology of the midface and oronasal regions of the face, but morphological differences were also found in the upper facial skeleton and to a lesser extent, the lower facial skeleton. This pattern of strong differences in the oronasal region of the facial skeleton combined with differences across the rest of the facial complex underscores the idea that bones of the craniofacial skeleton are integrated. © 2015 Wiley Periodicals, Inc.

Dental and skeletal maturation in female adolescents with temporomandibular joint osteoarthritis.

PubMed

Kang, J-H; Yang, I-H; Hyun, H-K; Lee, J-Y

2017-11-01

Occurrence of temporomandibular disorders (TMDs) and temporomandibular joint (TMJ) osteoarthritis (OA) during adolescence may have interactions with mandibular and dental development. The aim of the present study was to investigate relationships between occurrence of TMD and TMJ OA and extents of dental and skeletal development in juvenile female patients. In total, 95 female adolescents (age range, 11-15 years) were selected. Among them, 15 subjects (control) had no signs of TMD, 39 TMD patients did not have OA (TMDnoOA), 17 TMD patients were at initial stage of TMJ OA (TMJOA), and 27 patients showed progressive stage of TMJ OA (TMJOA). Dental age was estimated by Demirjian's stages used in a previous study with Korean adolescents. Craniofacial parameters and cervical vertebrae maturation (CVM) stages, representing skeletal maturity levels, were measured using lateral cephalograms. The estimated dental age was significantly lower than chronological age in all groups, but CVM differences were not statistically significant. Dental age was the lowest, and differences between the chronological age and estimated dental age were the highest among initial stage of TMJOAs followed by progressive stage of TMJOAs, TMDnoOAs and control and were not associated with CVM stages. Cephalometric parameters revealed significant clockwise rotation of the mandible among the TMJOAs compared with controls and TMDnoOAs and were not associated with CVM stages as well. The juvenile female patients with TMD, particularly TMJ OA, showed retarded dental development, mandibular backward positioning and hyperdivergent facial profiles. The TMJ OA may be associated with retarded dental development but not with skeletal maturations. © 2017 John Wiley & Sons Ltd.

The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis

PubMed Central

Rachmiel, Adi

2014-01-01

Summary: Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-β, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2) and extracellular matrix proteins (osteonectin, osteopontin) during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration. PMID:25289295

Maxillomandibular Volume Influences the Relationship between Weight Loss and Improvement in Obstructive Sleep Apnea

PubMed Central

Sutherland, Kate; Phillips, Craig L.; Yee, Brendon J.; Grunstein, Ronald R.; Cistulli, Peter A.

2016-01-01

Study Objectives: Obesity is the major risk factor for OSA; however, weight loss reduces OSA to a variable extent. We aimed to assess whether size of the maxillomandibular skeletal enclosure influences the relationship between weight loss and OSA reduction. Methods: Obese males (≥ 30 kg/m2) with moderate-severe OSA (AHI > 15/h) participating in a 6-mo open-label weight loss program had craniofacial computed tomography (CT) scans before and after weight loss. CT scans were analysed using three-dimensional cephalometry. Maxillomandibular volume was calculated from skeletal landmarks on the mandible (condyle, gonion, menton) and maxilla (anterior nasal spine). Multiple regression analysis was used to test for moderating effects of maxillomandibular volume on relationship between changes in weight and apnea-hypopnea index (AHI). Results: Fifty-two men (age 44.3 ± 8.8 y, AHI 42.9 ± 21.3 events/h, body mass index [BMI] 34.0 ± 2.7 kg/m2) had 7.4 ± 4.1% weight loss and 34.1 ± 32.4% AHI reduction at 6 months. BMI reduction modestly predicted AHI change (r2 = 0.17, P = 0.002). The interaction term of maxillomandibular volume and BMI change was a predictor of OSA improvement (P = 0.03), indicating maxillomandibular volume moderates this relationship. Subgroup analyses of patients by small, medium, and large maxillomandibular volume showed a strong correlation between weight loss and OSA improvement only in the small volume group (r = 0.654, P = 0.004). There was no relationship evident in those with large maxillomandibular volume (r = 0.05, P = 0.9). Conclusion: Maxillomandibular volume influences the relationship between weight loss and OSA improvement with an effect on AHI more evident in those with a smaller craniofacial skeleton. Citation: Sutherland K, Phillips CL, Yee BJ, Grunstein RR, Cistulli PA. Maxillomandibular volume influences the relationship between weight loss and improvement in obstructive sleep apnea. SLEEP 2016;39(1):43–49. PMID:26350470

Analysis of Practice Settings for Craniofacial Surgery Fellowship Graduates in North America.

PubMed

Silvestre, Jason; Runyan, Christopher; Taylor, Jesse A

In North America, the number of craniofacial surgery fellowship graduates is increasing, yet an analysis of practice settings upon graduation is lacking. We characterize the practice types of recent graduates of craniofacial fellowship programs in the United States and Canada. A 6-year cohort of craniofacial fellows in the United States and Canada (2010-2016) were obtained from craniofacial programs recognized by the American Society of Craniofacial Surgery. Practice setting was determined at 1 and 3 years of postgraduation, and predictors of practice setting were determined. A total of 175 craniofacial surgeons were trained at 35 fellowship programs. At 1 year of postgraduation, 33.6% had an academic craniofacial position and 27.1% were in private practice (p = 0.361). A minority of graduates pursued additional fellowships (16.4%), nonacademic craniofacial positions (10.0%), academic noncraniofacial positions (5.7%), and international practices (7.1%). At 3 years of postgraduation, the percentage of graduates in academic craniofacial positions was unchanged (34.5% vs 33.6%, p = 0.790). The strongest predictors of future academic craniofacial practice were completing plastic surgery residency at a program with a craniofacial fellowship program (odds ratio = 6.78, p < 0.001) and completing an academic craniofacial fellowship program (odds ratio = 4.48, p = 0.020). A minority of craniofacial fellowship graduates practice academic craniofacial surgery. A strong academic craniofacial surgery background during residency and fellowship is associated with a future career in academic craniofacial surgery. These data may assist trainees choose training programs that align with career goals and educators select future academic surgeons. Copyright © 2017. Published by Elsevier Inc.

The Effect of Conditional Inactivation of Beta 1 Integrins using Twist 2 Cre, Osterix Cre and Osteocalcin Cre Lines on Skeletal Phenotype

PubMed Central

Shekaran, Asha; Shoemaker, James T.; Kavanaugh, Taylor E.; Lin, Angela S.; LaPlaca, Michelle C.; Fan, Yuhong; Guldberg, Robert E.; García, Andrés J.

2014-01-01

Skeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions. While multiple in vitro studies indicate that β1 integrins are crucial regulators of osteogenesis and mineralization, in vivo osteoblast-specific perturbations of β1 integrins have resulted in mild and sometimes contradictory skeletal phenotypes. To further investigate the role of β1 integrins on skeletal phenotype, we used the Twist2-Cre, Osterix-Cre and Osteocalcin-Cre lines to generate conditional β1 integrin deletions, where cre is expressed primarily in mesenchymal condensation, pre-osteoblast, and mature osteoblast lineage cells respectively within these lines. Mice with Twist2-specific β1 integrin disruption were smaller, had impaired skeletal development, especially in the craniofacial and vertebral tissues at E19.5, and did not survive beyond birth. Osterix-specific β1 integrin deficiency resulted in viable mice which were normal at birth but displayed early defects in calvarial ossification, incisor eruption and growth as well as femoral bone mineral density, structure, and mechanical properties. Although these defects persisted into adulthood, they became milder with age. Finally, a lack of β1 integrins in mature osteoblasts and osteocytes resulted in minor alterations to femur structure but had no effect on mineral density, biomechanics or fracture healing. Taken together, our data indicate that β1 integrin expression in early mesenchymal condensations play an important role in skeletal ossification, while β1 integrin-ECM interactions in pre-osteoblast, odontoblast- and hypertrophic chondryocyte- lineage cells regulate incisor eruption and perinatal bone formation in both intramembranously and endochondrally formed bones in young, rapidly growing mice. In contrast, the Osteocalcin-specific β1 integrin deletion had only minor effects on skeletal phenotype. PMID:25183373

Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development

PubMed Central

Zhao, Chengtian; Andreeva, Viktoria; Gibert, Yann; LaBonty, Melissa; Lattanzi, Victoria; Prabhudesai, Shubhangi; Zhou, Yi; Zon, Leonard; McCann, Kathleen L.; Baserga, Susan; Yelick, Pamela C.

2014-01-01

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. PMID:24497835

Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome.

PubMed

Dixon, J; Brakebusch, C; Fässler, R; Dixon, M J

2000-06-12

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human craniofacial development that results from loss-of-function mutations in the gene TCOF1. Although this gene has been demonstrated to encode the nucleolar phosphoprotein treacle, the developmental mechanism underlying TCS remains elusive, particularly as expression studies have shown that the murine orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highest levels of Tcof1 expression. Our results demonstrate that TCS arises from haploinsufficiency of a protein that plays a crucial role in craniofacial development and indicate that correct dosage of treacle is essential for survival of cephalic neural crest cells.

Gorlin-Goltz Syndrome: An Uncommon Cause of Facial Pain and Asymmetry.

PubMed

Pickrell, Brent B; Nguyen, Harrison P; Buchanan, Edward P

2015-10-01

Gorlin-Goltz syndrome is an underdiagnosed autosomal dominant disorder with variable expressivity that is characterized by an increased predisposition to tumorigenesis of multiple types. The major clinical features include multiple basal cell carcinomas (BCCs) appearing in early childhood, palmar and plantar pits, odontogenic keratocysts of the oral cavity, skeletal defects, craniofacial dysmorphism, and ectopic intracranial calcification. The authors present the clinical course of a 12-year-old girl presenting with facial asymmetry and pain because of previously undiagnosed Gorlin-Goltz syndrome. Early diagnosis and attentive management by a multidisciplinary team are paramount to improving outcomes in patients with this disorder, and this report serves as a paradigm for maintaining a high clinical suspicion, which must be accompanied by an appropriate radiologic workup.

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: Population affinities and pathological abnormalities

PubMed Central

Jacob, T.; Indriati, E.; Soejono, R. P.; Hsü, K.; Frayer, D. W.; Eckhardt, R. B.; Kuperavage, A. J.; Thorne, A.; Henneberg, M.

2006-01-01

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose that LB1 is drawn from an earlier pygmy H. sapiens population but individually shows signs of a developmental abnormality, including microcephaly. Additional mandibular and postcranial remains from the site share small body size but not microcephaly. PMID:16938848

Developmental mechanisms underlying variation in craniofacial disease and evolution.

PubMed

Fish, Jennifer L

2016-07-15

Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. Copyright © 2015 Elsevier Inc. All rights reserved.

Psychometric evaluation of a motor control test battery of the craniofacial region.

PubMed

von Piekartz, H; Stotz, E; Both, A; Bahn, G; Armijo-Olivo, S; Ballenberger, N

2017-12-01

The primary objective of this study was to determine the structural and known-group validity as well as the inter-rater reliability of a test battery to evaluate the motor control of the craniofacial region. Seventy volunteers without TMD and 25 subjects with TMD (Axes I) per the DC/TMD were asked to execute a test battery consisting of eight tests. The tests were video-taped in the same sequence in a standardised manner. Two experienced physical therapists participated in this study as blinded assessors. We used exploratory factor analysis to identify the underlying component structure of the eight tests. Internal consistency (Cronbach's α), inter-rater reliability (intra-class correlation coefficient) and construct validity (ie, hypothesis testing-known-group validity) (receiver operating curves) were also explored for the test battery. The structural validity showed the presence of one factor underlying the construct of the test battery. The internal consistency was excellent (0.90) as well as the inter-rater reliability. All values of reliability were close to 0.9 or above indicating very high inter-rater reliability. The area under the curve (AUC) was 0.93 for rater 1 and 0.94 for rater two, respectively, indicating excellent discrimination between subjects with TMD and healthy controls. The results of the present study support the psychometric properties of test battery to measure motor control of the craniofacial region when evaluated through videotaping. This test battery could be used to differentiate between healthy subjects and subjects with musculoskeletal impairments in the cervical and oro-facial regions. In addition, this test battery could be used to assess the effectiveness of management strategies in the craniofacial region. © 2017 John Wiley & Sons Ltd.

Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome.

PubMed

van Gijn, Daniel Richard; Tucker, Abigail S; Cobourne, Martyn T

2013-07-01

The human face and skull are an elegant example of the anatomical sophistication that results from the interplay between the molecular cascades and the tissue interactions that are necessary for the proper development of the craniofacial complex. When it fails to develop normally the consequences can have life-long implications for the biological, psychological, and aesthetic wellbeing of an affected person. Among the many syndromes that affect the region, understanding of the biology that underlies Treacher Collins syndrome has advanced in the last decade, particularly concerning the causative TCOF1 gene that encodes TREACLE protein, a serine/alanine-rich nucleolar phosphoprotein with an essential function during ribosome biogenesis in cranial neural crest cells. Abnormal growth and differentiation of these cells affect much of the craniofacial skeleton. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Cephalometric evaluation of the effects of the Twin Block appliance in subjects with Class II, Division 1 malocclusion amongst different cervical vertebral maturation stages.

PubMed

Khoja, Aisha; Fida, Mubassar; Shaikh, Attiya

2016-06-01

To evaluate the cephalometric changes in skeletal, dentoalveolar and soft tissue variables induced by Clark's Twin Block (CTB) in Class II, Division 1 malocclusion patients and to compare these changes in different cervical vertebral maturation stages. Pre- and post-treatment/observation lateral cephalograms of 53 Class II, Division 1 malocclusion patients and 60 controls were compared to evaluate skeletal, dentoalveolar and soft tissue changes. Skeletal maturity was assessed according to cervical vertebral maturation stages. Pre- and post-treatment/observation mean changes and differences (T2-T1) were compared by means of Wilcoxon sign rank and Mann-Whitney U-tests, respectively. Intergroup comparisons between different cervical stages were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (p ≤ 0.05) . When compared with controls, there was a significant reduction in ANB angle (p < 0.001), which was due to a change in SNB angle in CS-2 and CS-3 (p < 0.001), and in SNA (p < 0.001) and SNB (p = 0.016) angles in the CS-4 group. There was significant increase in the GoGn-SN angle in CS-2 (p = 0.007) and CS-4 (p = 0.024), and increase in Co-Gn and Go-Gn amongst all cervical stages (p < 0.05). There was significant decrease in U1-SN and increase in IMPA amongst all cervical stages (p < 0.05). There was significant retraction of the upper lip in CS-3 (p = 0.001), protrusion of the lower lip in CS-2 (p = 0.005), increase in nasolabial angle in CS-4 (p = 0.006) and Z-angle in CS-3 (p = 0.016), reduction in H-angle in CS-2 (p = 0.013) and CS-3 (p = 0.002) groups. When pre- and post-treatment mean differences were compared between different cervical stages, significant differences were found for SNA, SNB and UI-SN angles and overjet. . The Twin-Block along with the normal craniofacial growth improves facial esthetics in Class II, Division 1 malocclusion by changes in underlying skeletal and dentoalveolar structures. The favorable mandibular growth occurs during any of the cervical vertebral maturation stages, with more pronounced effect during CS-3 stage.

Cephalometric evaluation of the effects of the Twin Block appliance in subjects with Class II, Division 1 malocclusion amongst different cervical vertebral maturation stages

PubMed Central

Khoja, Aisha; Fida, Mubassar; Shaikh, Attiya

2016-01-01

ABSTRACT Objectives: To evaluate the cephalometric changes in skeletal, dentoalveolar and soft tissue variables induced by Clark's Twin Block (CTB) in Class II, Division 1 malocclusion patients and to compare these changes in different cervical vertebral maturation stages. Methods: Pre- and post-treatment/observation lateral cephalograms of 53 Class II, Division 1 malocclusion patients and 60 controls were compared to evaluate skeletal, dentoalveolar and soft tissue changes. Skeletal maturity was assessed according to cervical vertebral maturation stages. Pre- and post-treatment/observation mean changes and differences (T2-T1) were compared by means of Wilcoxon sign rank and Mann-Whitney U-tests, respectively. Intergroup comparisons between different cervical stages were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (p ≤ 0.05) . Results: When compared with controls, there was a significant reduction in ANB angle (p < 0.001), which was due to a change in SNB angle in CS-2 and CS-3 (p < 0.001), and in SNA (p < 0.001) and SNB (p = 0.016) angles in the CS-4 group. There was significant increase in the GoGn-SN angle in CS-2 (p = 0.007) and CS-4 (p = 0.024), and increase in Co-Gn and Go-Gn amongst all cervical stages (p < 0.05). There was significant decrease in U1-SN and increase in IMPA amongst all cervical stages (p < 0.05). There was significant retraction of the upper lip in CS-3 (p = 0.001), protrusion of the lower lip in CS-2 (p = 0.005), increase in nasolabial angle in CS-4 (p = 0.006) and Z-angle in CS-3 (p = 0.016), reduction in H-angle in CS-2 (p = 0.013) and CS-3 (p = 0.002) groups. When pre- and post-treatment mean differences were compared between different cervical stages, significant differences were found for SNA, SNB and UI-SN angles and overjet. . Conclusions: The Twin-Block along with the normal craniofacial growth improves facial esthetics in Class II, Division 1 malocclusion by changes in underlying skeletal and dentoalveolar structures. The favorable mandibular growth occurs during any of the cervical vertebral maturation stages, with more pronounced effect during CS-3 stage. PMID:27409656

An automatic method for skeletal patterns classification using craniomaxillary variables on a Colombian population.

PubMed

Niño-Sandoval, Tania Camila; Guevara Perez, Sonia V; González, Fabio A; Jaque, Robinson Andrés; Infante-Contreras, Clementina

2016-04-01

The mandibular bone is an important part of the forensic facial reconstruction and it has the possibility of getting lost in skeletonized remains; for this reason, it is necessary to facilitate the identification process simulating the mandibular position only through craniomaxillary measures, for this task, different modeling techniques have been performed, but they only contemplate a straight facial profile that belong to skeletal pattern Class I, but the 24.5% corresponding to the Colombian skeletal patterns Class II and III are not taking into account, besides, craniofacial measures do not follow a parametric trend or a normal distribution. The aim of this study was to employ an automatic non-parametric method as the Support Vector Machines to classify skeletal patterns through craniomaxillary variables, in order to simulate the natural mandibular position on a contemporary Colombian sample. Lateral cephalograms (229) of Colombian young adults of both sexes were collected. Landmark coordinates protocols were used to create craniomaxillary variables. A Support Vector Machine with a linear kernel classifier model was trained on a subset of the available data and evaluated over the remaining samples. The weights of the model were used to select the 10 best variables for classification accuracy. An accuracy of 74.51% was obtained, defined by Pr-A-N, N-Pr-A, A-N-Pr, A-Te-Pr, A-Pr-Rhi, Rhi-A-Pr, Pr-A-Te, Te-Pr-A, Zm-A-Pr and PNS-A-Pr angles. The Class Precision and the Class Recall showed a correct distinction of the Class II from the Class III and vice versa. Support Vector Machines created an important model of classification of skeletal patterns using craniomaxillary variables that are not commonly used in the literature and could be applicable to the 24.5% of the contemporary Colombian sample. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oral appliances and functional orthopaedic appliances for obstructive sleep apnoea in children.

PubMed

Carvalho, F R; Lentini-Oliveira, D; Machado, M A C; Prado, G F; Prado, L B F; Saconato, H

2007-04-18

Apnoea is a breathing disorder marked by the absence of airflow at the nose or mouth. In children, risk factors include adenotonsillar hypertrophy, obesity, neuromuscular disorders and craniofacial anomalies. The most common treatment for obstructive sleep apnoea syndrome (OSAS) in childhood is adenotonsillectomy. This approach is limited by its surgical risks, mostly in children with comorbities and, in some patients, by recurrence that can be associated with craniofacial problems. Oral appliances and functional orthopaedic appliances have been used for patients who have OSAS and craniofacial anomalies because they change the mandible posture forwards and potentially enlarge the upper airway and increase the upper airspace, improving the respiratory function. To assess the effectiveness of oral appliances or functional orthopaedic appliances for OSAS in children. A sensitive search was developed for the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 3); PubMed (January 1966 to September 2005); EMBASE (1980 to September 2005); Lilacs (1982 to September 2005); BBO-Bibliografia Brasileira de Odontologia (1986 to September 2005); and SciELO (1997 to September 2005). There was no restriction of language or source of information. All randomised or quasi-randomised controlled trials comparing all types of oral and functional orthopaedic appliances with placebo or no treatment, in children 15 years old or younger. reduction of apnoea to less than one episode per hour. dental and skeletal relationship, sleep parameters improvement, cognitive and phonoaudiologic function, behavioural problems, drop outs and withdrawals, quality of life, side effects (tolerability), economic evaluation. Data were independently extracted by two review authors. Authors were contacted for additional information. Risk ratios with 95% confidence intervals were calculated for all important dichotomous outcomes. The initial search identified 384 trials. One of them, reporting results from a total of 23 patients, was suitable for inclusion in the review. Data provided in the published report did not answer all the questions from this review, but some of them were, and the presented results favour treatment. At present there is no sufficient evidence to state that oral appliances or functional orthopaedic appliances are effective in the treatment of OSAS in children. Oral appliances or functional orthopaedic appliances may be helpful in the treatment of children with craniofacial anomalies which are risk factors for apnoea.

Epigenetically Modified Bone Marrow Stromal Cells in Silk Scaffolds Promote Craniofacial Bone Repair and Wound Healing.

PubMed

Han, Qianqian; Yang, Pishan; Wu, Yuwei; Meng, Shu; Sui, Lei; Zhang, Lan; Yu, Liming; Tang, Yin; Jiang, Hua; Xuan, Dongying; Kaplan, David L; Kim, Sung Hoon; Tu, Qisheng; Chen, Jake

2015-08-01

Epigenetic regulation of gene expression is a central mechanism that governs cell stemness, determination, commitment, and differentiation. It has been recently found that PHF8, a major H4K20/H3K9 demethylase, plays a critical role in craniofacial and bone development. In this study, we hypothesize that PHF8 promotes osteoblastogenesis by epigenetically regulating the expression of a nuclear matrix protein, special AT-rich sequence-binding protein 2 (SATB2) that plays pivotal roles in skeletal patterning and osteoblast differentiation. Our results showed that expression levels of PHF8 and SATB2 in preosteoblasts and bone marrow stromal cells (BMSCs) increased simultaneously during osteogenic induction. Overexpressing PHF8 in these cells upregulated the expression of SATB2, Runx2, osterix, and bone matrix proteins. Conversely, knockdown of PHF8 reduced the expression of these genes. Furthermore, ChIP assays confirmed that PHF8 specifically bound to the transcription start site (TSS) of the SATB2 promoter, and the expression of H3K9me1 at the TSS region of SATB2 decreased in PHF8 overexpressed group. Implantation of the BMSCs overexpressing PHF8 with silk protein scaffolds promoted bone regeneration in critical-sized defects in mouse calvaria. Taken together, our results demonstrated that PHF8 epigenetically modulates SATB2 activity, triggering BMSCs osteogenic differentiation and facilitating bone formation and regeneration in biodegradable silk scaffolds.

Obeservations on association between third molar agenesis and craniofacial morphology.

PubMed

Huang, Yi; Yan, Yinqiu; Cao, Jing; Xie, Bingjie; Xiao, Xueling; Luo, Mengqi; Bai, Ding; Han, Xianglong

2017-11-01

This study was designed to examine the relationship between third molar agenesis and skeletal morphology in the Chinese population. A total of 1043 patients' records were analyzed with panoramic radiographs and cephalograms. Congenitally missing third molars were assessed with respect to gender, jaw, and side, and assessed in various types of facial morphology. Linear, angular, and proportional cephalometric measurements were analyzed and compared among the samples. For the evaluation of results, the following statistics were used: the Pearson χ 2 test, one-way ANOVA, and the Student-Newman-Keuls method. The overall prevalence of third molar agenesis was 28.7%. Missing third molars were more common in the maxilla and on the right side, while the difference was not statistically significant (P > 0.05) between genders. Every hypodontia group had a smaller SN-GoGn angle, Y-axis-FH angle, and a larger S-Go/N-Me ratio. The group with third molar agenesis in both jaws had smaller SNA and Wits values. The frequency of third molar agenesis in subjects with a Class II malocclusion was significantly lower than in other types of malocclusion (P < 0.05), and the incidence of third molar agenesis in hypodivergent growth pattern was higher than in other patterns (P < 0.05). The results demonstrate a possible association between third molar agenesis and both sagittal and vertical craniofacial morphology.

The role of 3D printing in treating craniomaxillofacial congenital anomalies.

PubMed

Lopez, Christopher D; Witek, Lukasz; Torroni, Andrea; Flores, Roberto L; Demissie, David B; Young, Simon; Cronstein, Bruce N; Coelho, Paulo G

2018-05-20

Craniomaxillofacial congenital anomalies comprise approximately one third of all congenital birth defects and include deformities such as alveolar clefts, craniosynostosis, and microtia. Current surgical treatments commonly require the use of autogenous graft material which are difficult to shape, limited in supply, associated with donor site morbidity and cannot grow with a maturing skeleton. Our group has demonstrated that 3D printed bio-ceramic scaffolds can generate vascularized bone within large, critical-sized defects (defects too large to heal spontaneously) of the craniomaxillofacial skeleton. Furthermore, these scaffolds are also able to function as a delivery vehicle for a new osteogenic agent with a well-established safety profile. The same 3D printers and imaging software platforms have been leveraged by our team to create sterilizable patient-specific intraoperative models for craniofacial reconstruction. For microtia repair, the current standard of care surgical guide is a two-dimensional drawing taken from the contralateral ear. Our laboratory has used 3D printers and open source software platforms to design personalized microtia surgical models. In this review, we report on the advancements in tissue engineering principles, digital imaging software platforms and 3D printing that have culminated in the application of this technology to repair large bone defects in skeletally immature transitional models and provide in-house manufactured, sterilizable patient-specific models for craniofacial reconstruction. © 2018 Wiley Periodicals, Inc.

Expression of Glycosaminoglycan Epitopes During Zebrafish Skeletogenesis

PubMed Central

Hayes, Anthony J; Mitchell, Ruth E; Bashford, Andrew; Reynolds, Scott; Caterson, Bruce; Hammond, Chrissy L

2013-01-01

Background: The zebrafish is an important developmental model. Surprisingly, there are few studies that describe the glycosaminoglycan composition of its extracellular matrix during skeletogenesis. Glycosaminoglycans on proteoglycans contribute to the material properties of musculo skeletal connective tissues, and are important in regulating signalling events during morphogenesis. Sulfation motifs within the chain structure of glycosaminoglycans on cell-associated and extracellular matrix proteoglycans allow them to bind and regulate the sequestration/presentation of bioactive signalling molecules important in musculo-skeletal development. Results: We describe the spatio-temporal expression of different glycosaminoglycan moieties during zebrafish skeletogenesis with antibodies recognising (1) native sulfation motifs within chondroitin and keratan sulfate chains, and (2) enzyme-generated neoepitope sequences within the chain structure of chondroitin sulfate (i.e., 0-, 4-, and 6-sulfated isoforms) and heparan sulfate glycosaminoglycans. We show that all the glycosaminoglycan moieties investigated are expressed within the developing skeletal tissues of larval zebrafish. However, subtle changes in their patterns of spatio-temporal expression over the period examined suggest that their expression is tightly and dynamically controlled during development. Conclusions: The subtle differences observed in the domains of expression between different glycosaminoglycan moieties suggest differences in their functional roles during establishment of the primitive analogues of the skeleton. Developmental Dynamics 242:778–789, 2013. © 2013 Wiley Periodicals, Inc. Key Findings The developing zebrafish skeleton expresses many different glycosaminoglycan modifications. Multiple different glycosaminoglycan epitopes are dynamically expressed in the craniofacial skeleton. Expression of chondroitin sulfate moieties are dynamically expressed in the vertebral column and precede mineralisation. PMID:23576310

A Multivariate Analysis of Unilateral Cleft Lip and Palate Facial Skeletal Morphology.

PubMed

Starbuck, John M; Ghoneima, Ahmed; Kula, Katherine

2015-07-01

Unilateral cleft lip and palate (UCLP) occurs when the maxillary and nasal facial prominences fail to fuse correctly during development, resulting in a palatal cleft and clefted soft and hard tissues of the dentoalveolus. The UCLP deformity may compromise an individual's ability to eat, chew, and speak. In this retrospective cross-sectional study, cone beam computed tomography (CBCT) images of 7-17-year-old individuals born with UCLP (n = 24) and age- and sex-matched controls (n = 24) were assessed. Coordinate values of three-dimensional anatomical landmarks (n = 32) were recorded from each CBCT image. Data were evaluated using principal coordinates analysis (PCOORD) and Euclidean distance matrix analysis (EDMA). Approximately 40% of morphometric variation is captured by PCOORD axes 1-3, and the negative and positive ends of each axis are associated with specific patterns of morphological differences. Approximately 36% of facial skeletal measures significantly differ by confidence interval testing (α = 0.10) between samples. Although significant form differences occur across the facial skeleton, strong patterns of morphological differences were localized to the lateral and superioinferior aspects of the nasal aperture, particularly on the clefted side of the face. The UCLP deformity strongly influences facial skeletal morphology of the midface and oronasal facial regions, and to a lesser extent the upper and lower facial skeletons. The pattern of strong morphological differences in the oronasal region combined with differences across the facial complex suggests that craniofacial bones are integrated and covary, despite influences from the congenital cleft.

Influence of maxillary posterior discrepancy on upper molar vertical position and facial vertical dimensions in subjects with or without skeletal open bite

PubMed Central

Aliaga-Del Castillo, Aron; Pérez-Vargas, Luis Fernando; Flores-Mir, Carlos

2016-01-01

Summary Objectives: To determine the influence of maxillary posterior discrepancy on upper molar vertical position and dentofacial vertical dimensions in individuals with or without skeletal open bite (SOB). Materials and methods: Pre-treatment lateral cephalograms of 139 young adults were examined. The sample was divided into eight groups categorized according to their sagittal and vertical skeletal facial growth pattern and maxillary posterior discrepancy (present or absent). Upper molar vertical position, overbite, lower anterior facial height and facial height ratio were measured. Independent t-test was performed to determine differences between the groups considering maxillary posterior discrepancy. Principal component analysis and MANCOVA test were also used. Results: No statistically significant differences were found comparing the molar vertical position according to maxillary posterior discrepancy for the SOB Class I group or the group with adequate overbite. Significant differences were found in SOB Class II and Class III groups. In addition, an increased molar vertical position was found in the group without posterior discrepancy. Limitations: Some variables closely related with the individual’s intrinsic craniofacial development that could influence the evaluated vertical measurements were not considered. Conclusions and implications: Overall maxillary posterior discrepancy does not appear to have a clear impact on upper molar vertical position or facial vertical dimensions. Only the SOB Class III group without posterior discrepancy had a significant increased upper molar vertical position. PMID:26385786

Influence of maxillary posterior discrepancy on upper molar vertical position and facial vertical dimensions in subjects with or without skeletal open bite.

PubMed

Arriola-Guillén, Luis Ernesto; Aliaga-Del Castillo, Aron; Pérez-Vargas, Luis Fernando; Flores-Mir, Carlos

2016-06-01

To determine the influence of maxillary posterior discrepancy on upper molar vertical position and dentofacial vertical dimensions in individuals with or without skeletal open bite (SOB). Pre-treatment lateral cephalograms of 139 young adults were examined. The sample was divided into eight groups categorized according to their sagittal and vertical skeletal facial growth pattern and maxillary posterior discrepancy (present or absent). Upper molar vertical position, overbite, lower anterior facial height and facial height ratio were measured. Independent t-test was performed to determine differences between the groups considering maxillary posterior discrepancy. Principal component analysis and MANCOVA test were also used. No statistically significant differences were found comparing the molar vertical position according to maxillary posterior discrepancy for the SOB Class I group or the group with adequate overbite. Significant differences were found in SOB Class II and Class III groups. In addition, an increased molar vertical position was found in the group without posterior discrepancy. Some variables closely related with the individual's intrinsic craniofacial development that could influence the evaluated vertical measurements were not considered. Overall maxillary posterior discrepancy does not appear to have a clear impact on upper molar vertical position or facial vertical dimensions. Only the SOB Class III group without posterior discrepancy had a significant increased upper molar vertical position. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Fibroblast growth factor (FGF) signaling in development and skeletal diseases.

PubMed

Teven, Chad M; Farina, Evan M; Rivas, Jane; Reid, Russell R

2014-12-01

Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

Fibroblast growth factor (FGF) signaling in development and skeletal diseases

PubMed Central

Teven, Chad M.; Farina, Evan M.; Rivas, Jane; Reid, Russell R.

2014-01-01

Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development. PMID:25679016

The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction

PubMed Central

Jin, Yong-Ri; Turcotte, Taryn J.; Crocker, Alison L.; Han, Xiang Hua; Yoon, Jeong Kyo

2011-01-01

R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate. We found that loss of the mouse Rspo2 gene significantly disrupted Wnt/β-catenin signaling and gene expression within the first branchial arch (BA1). Rspo2, which is normally expressed in BA1 mesenchymal cells, regulates gene expression through a unique ectoderm-mesenchyme interaction loop. The Rspo2 protein, potentially in combination with ectoderm-derived Wnt ligands, up-regulates Msx1 and Msx2 expression within mesenchymal cells. In contrast, Rspo2 regulates expression of the Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells. Loss of Rspo2 also causes increased cell apoptosis, especially within the aboral (or caudal) domain of the BA1, resulting in hypoplasia of the BA1. Severely reduced expression of Fgf8, a survival factor for mesenchymal cells, in the ectoderm of Rspo2−/− embryos is likely responsible for increased cell apoptosis. Additionally, we found that cleft palate in Rspo2−/− mice is not associated with defects intrinsic to the palatal shelves. A possible cause of cleft palate is a delay of proper palatal shelf elevation that may result from the small mandible and a failure of lowering the tongue. Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. PMID:21237142

Multiple tooth anomalies in a nonsyndromic patient with class II division 2 malocclusions: A case report and a literature review.

PubMed

Isman, E; Isman, O; Aktan, A M; Ciftci, E; Topcuoglu, T

2015-01-01

Reports in the literature about the craniofacial characteristics of patients with class II division 2 malocclusions show a lot of different patterns accompanied by palatally displaced upper incisors, congenital missing teeth, polydiastema, fusion, germination, tooth impaction, peg-shaped lateral incisors, persistent teeth, hypodontia, persistent deciduous teeth, transpositions, and supernumerary teeth. The following case report focuses on the description of the clinical characteristics observed on a patient with a very unusual conjunction of dental and skeletal anomalies mentioned above, as well as a literature review on the related issues. Extra-intra-oral examinations, radiographic evaluations, orthodontic consultation, and reviewing the literature concluded that this nonsyndromic patient that refused to receive all dental treatment approaches is special with its uniqueness.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

PubMed

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. Copyright © 2016 Elsevier Inc. All rights reserved.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of themore » craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.« less

Modeling human craniofacial disorders in Xenopus

PubMed Central

Dubey, Aditi; Saint-Jeannet, Jean-Pierre

2017-01-01

Purpose of Review Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. Recent findings The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population. Therefore, defining the pathogenesis of these conditions starts with a deep understanding of the mechanisms that preside over neural crest formation and its role in craniofacial development. Summary This review discusses several studies using Xenopus embryos to model human craniofacial conditions, and emphasizes the strength of this system to inform important biological processes as they relate to human craniofacial development and disease. PMID:28255527

Craniofacial variation and dietary adaptations of African colobines.

PubMed

Koyabu, Daisuke B; Endo, Hideki

2009-06-01

African colobine monkeys show considerable craniofacial variation among species, although the evolutionary causes of this diversity are unclear. In light of growing evidence that diet varies considerably among colobine species, we investigated whether colobine craniofacial morphology varies as a function of their diet. We compared craniofacial morphology among five African species: Colobus angolensis, C. guereza, C. polykomos, Piliocolobus badius, and P. verus. Matrix correlation analysis indicated a significant correlation between species-specific morphological distance and dietary distance matrices. The mechanical advantage of the masseter muscle was higher in seed-eaters (C. angolensis and C. polykomos) and lower in those that eat mainly young leaves (C. guereza, P. badius, and P. verus). Canonical correspondence analysis revealed that the durophagous colobines possess relatively wider bigonial breadths, anteroposteriorly shorter faces, shorter postcanine tooth rows, more medially positioned dental batteries, wider bizygomatic arches, and anteroposteriorly longer zygomatic arches. Under the constrained lever model, these morphological features suggest that durophagous colobines have the capacity to generate relatively greater maximum bite forces. However, no consistent relationship was observed between diet and variation in the mandibular corpus and symphysis, implying that robust mandibles are not necessarily adaptations for stress resistance. Factors that may influence mandibular robusticity include allometry of symphyseal curvature and canine tooth support. Finally, linear measures of mandibular robusticity may suffer from error.

Craniofacial Tissue Engineering by Stem Cells

PubMed Central

Mao, J.J.; Giannobile, W.V.; Helms, J.A.; Hollister, S.J.; Krebsbach, P.H.; Longaker, M.T.; Shi, S.

2008-01-01

Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures—such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue—have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. PMID:17062735

Age- and sex-related growth patterns of the craniofacial complex in European children aged 3-6 years.

PubMed

Tutkuviene, Janina; Cattaneo, Cristina; Obertová, Zuzana; Ratnayake, Melanie; Poppa, Pasquale; Barkus, Arunas; Khalaj-Hedayati, Kerstin; Schroeder, Inge; Ritz-Timme, Stefanie

2016-11-01

Craniofacial growth changes in young children are not yet completely understood. Up-to-date references for craniofacial measurements are crucial for clinical assessment of orthodontic anomalies, craniofacial abnormalities and subsequent planning of interventions. To provide normal reference data and to identify growth patterns for craniofacial dimensions of European boys and girls aged 3-6 years. Using standard anthropometric methodology, body weight, body height and 23 craniofacial measurements were acquired for a cross-sectional sample of 681 healthy children (362 boys and 319 girls) aged 3-6 years from Germany, Italy and Lithuania. Descriptive statistics, correlation coefficients, percentage annual changes and percentage growth rates were used to analyse the dataset. Between the ages of 3-6 years, craniofacial measurements showed age- and sex-related patterns independent from patterns observed for body weight and body height. Sex-related differences were observed in the majority of craniofacial measurements. In both sexes, face heights and face depths showed the strongest correlation with age. Growth patterns differed by craniofacial measurement and can be summarised into eight distinct age- and sex-related patterns. This study provided reference data and identified sex- and age-related growth patterns of the craniofacial complex of young European children, which may be used for detailed assessment of normal growth in paediatrics, maxillofacial reconstructive surgery and possibly for forensic age assessment.

3D craniofacial registration using thin-plate spline transform and cylindrical surface projection

PubMed Central

Chen, Yucong; Deng, Qingqiong; Duan, Fuqing

2017-01-01

Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF) for the reference craniofacial model. Second, the thin-plate spline transform (TPST) is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP) is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate. PMID:28982117

3D craniofacial registration using thin-plate spline transform and cylindrical surface projection.

PubMed

Chen, Yucong; Zhao, Junli; Deng, Qingqiong; Duan, Fuqing

2017-01-01

Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF) for the reference craniofacial model. Second, the thin-plate spline transform (TPST) is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP) is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate.

Development: facial makeup enhancing our looks.

PubMed

Rohner, Nicolas; Tschopp, Patrick; Tabin, Cliff

2014-01-06

A recent study in mice deciphers the complex genetic regulatory network underlying the morphogenesis of the face. The enhancer landscape underlying craniofacial development provides multiple entry points to understand what makes up the face, in natural variation or pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function.

PubMed

Jones, Natalie C; Lynn, Megan L; Gaudenz, Karin; Sakai, Daisuke; Aoto, Kazushi; Rey, Jean-Phillipe; Glynn, Earl F; Ellington, Lacey; Du, Chunying; Dixon, Jill; Dixon, Michael J; Trainor, Paul A

2008-02-01

Treacher Collins syndrome (TCS) is a congenital disorder of craniofacial development arising from mutations in TCOF1, which encodes the nucleolar phosphoprotein Treacle. Haploinsufficiency of Tcof1 perturbs mature ribosome biogenesis, resulting in stabilization of p53 and the cyclin G1-mediated cell-cycle arrest that underpins the specificity of neuroepithelial apoptosis and neural crest cell hypoplasia characteristic of TCS. Here we show that inhibition of p53 prevents cyclin G1-driven apoptotic elimination of neural crest cells while rescuing the craniofacial abnormalities associated with mutations in Tcof1 and extending life span. These improvements, however, occur independently of the effects on ribosome biogenesis; thus suggesting that it is p53-dependent neuroepithelial apoptosis that is the primary mechanism underlying the pathogenesis of TCS. Our work further implies that neuroepithelial and neural crest cells are particularly sensitive to cellular stress during embryogenesis and that suppression of p53 function provides an attractive avenue for possible clinical prevention of TCS craniofacial birth defects and possibly those of other neurocristopathies.

Hush puppy: a new mouse mutant with pinna, ossicle, and inner ear defects.

PubMed

Pau, Henry; Fuchs, Helmut; de Angelis, Martin Hrabé; Steel, Karen P

2005-01-01

Deafness can be associated with abnormalities of the pinna, ossicles, and cochlea. The authors studied a newly generated mouse mutant with pinna defects and asked whether these defects are associated with peripheral auditory or facial skeletal abnormalities, or both. Furthermore, the authors investigated where the mutation responsible for these defects was located in the mouse genome. The hearing of hush puppy mutants was assessed by Preyer reflex and electrophysiological measurement. The morphological features of their middle and inner ears were investigated by microdissection, paint-filling of the labyrinth, and scanning electron microscopy. Skeletal staining of skulls was performed to assess the craniofacial dimensions. Genome scanning was performed using microsatellite markers to localize the mutation to a chromosomal region. Some hush puppy mutants showed early onset of hearing impairment. They had small, bat-like pinnae and normal malleus but abnormal incus and stapes. Some mutants had asymmetrical defects and showed reduced penetrance of the ear abnormalities. Paint-filling of newborns' inner ears revealed no morphological abnormality, although half of the mice studied were expected to carry the mutation. Reduced numbers of outer hair cells were demonstrated in mutants' cochlea on scanning electron microscopy. Skeletal staining showed that the mutants have significantly shorter snouts and mandibles. Genome scan revealed that the mutation lies on chromosome 8 between markers D8Mit58 and D8Mit289. The study results indicate developmental problems of the first and second branchial arches and otocyst as a result of a single gene mutation. Similar defects are found in humans, and hush puppy provides a mouse model for investigation of such defects.

Trends and Characteristics of Pediatric Dentistry Patients Treated under General Anesthesia.

PubMed

Rudie, Maxwell N; Milano, Michael M; Roberts, Michael W; Divaris, Kimon

2018-05-11

The aims of this study were to describe the demographic characteristics of pediatric dentistry patients undergoing dental rehabilitation under general anesthesia (DRGA) at UNC-Chapel Hill during the last 13 years and identify factors associated with multiple (1 versus 2 or more) DRGA visits during that timeframe. Administrative claims data were used to identify children and adolescents (age <18 years) who underwent DRGA between 1/1/2002 and 12/31/2014 at the UNC Hospitals system. Information on children's age, sex and all treatment-associated CDT codes were collected. Descriptive statistics and bivariate tests of association were used for data analyses. There were 4,413 DRGAs among 3,973 children (median age=4 years 8 months, males=55%) during the study period. The annual rate of DRGAs increased over time, peaking (n=447) in 2013. Overall, 9% of children had ≥2 visits with repeat rates up to 18%. There was no association between children's sex and receipt of one versus multiple DRGAs; however, craniofacial cases were more likely (p<0.0005) to have multiple DRGAs compared to non-craniofacial ones. DRGAs are on the increase-with the exception of craniofacial and special health care needs patients, multiple DRGAs may be reflective of sub-optimal adherence to preventive and continuing care recommendations.

Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

PubMed

Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

2014-08-01

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

Bone healing and bone substitutes.

PubMed

Costantino, Peter D; Hiltzik, David; Govindaraj, Satish; Moche, Jason

2002-02-01

With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.

The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery.

PubMed

Mahon, Nicola A; Joyce, Cormac W; Thomas, Sangeetha; Concannon, Elizabeth; Murray, Dylan

2015-09-01

Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty.

OCT imaging of craniofacial anatomy in xenopus embryos (Conference Presentation)

NASA Astrophysics Data System (ADS)

Deniz, Engin; Jonas, Stephan M.; Griffin, John; Hooper, Michael C.; Choma, Michael A.; Khokha, Mustafa K.

2016-03-01

The etiology of craniofacial defects is incompletely understood. The ability to obtain large amounts of gene sequence data from families affected by craniofacial defects is opening up new ways to understand molecular genetic etiological factors. One important link between gene sequence data and clinical relevance is biological research into candidate genes and molecular pathways. We present our recent research using OCT as a nondestructive phenotyping modality of craniofacial morphology in Xenopus embryos, an important animal model for biological research in gene and pathway discovery. We define 2D and 3D scanning protocols for a standardized approach to craniofacial imaging in Xenopus embryos. We define standard views and planar reconstructions for visualizing normal anatomy and landmarks. We compare these views and reconstructions to traditional histopathology using alcian blue staining. In addition to being 3D, nondestructive, and having much faster throughout, OCT can identify craniofacial features that are lost during traditional histopathological preparation. We also identify quantitative morphometric parameters to define normative craniofacial anatomy. We also note that craniofacial and cardiac defects are not infrequently present in the same patient (e.g velocardiofacial syndrome). Given that OCT excels at certain aspects of cardiac imaging in Xenopus embryos, our work highlights the potential of using OCT and Xenopus to study molecular genetic factors that impact both cardiac and craniofacial development.

[Fitting of the reconstructed craniofacial hard and soft tissues based on 2-D digital radiographs].

PubMed

Feng, Yao-Pu; Qiao, Min; Zhou, Hong; Zhang, Yan-Ning; Si, Xin-Qin

2017-02-01

In this study, we reconstructed the craniofacial hard and soft tissues based on the data from digital cephalometric radiographs and laser scanning. The effective fitting of the craniofacial hard and soft tissues was performed in order to increase the level of orthognathic diagnosis and treatment, and promote the communication between doctors and patients. A small lead point was put on the face of a volunteer and frontal and lateral digital cephalometric radiographs were taken. 3-D reconstruction system of the craniofacial hard tissue based on 2-D digital radiograph was used to get the craniofacial hard tissue model by means of hard tissue deformation modeling. 3-D model of facial soft tissue was obtained by using laser scanning data. By matching the lead point coordinate, the hard tissue and soft tissue were fitted. The 3-D model of the craniofacial hard and soft tissues was rebuilt reflecting the real craniofacial tissue structure, and effective fitting of the craniofacial hard and soft tissues was realized. The effective reconstruction and fitting of the 3-D craniofacial structures have been realized, which lays a foundation for further orthognathic simulation and facial appearance prediction. The fitting result is reliable, and could be used in clinical practice.

Influence of prenatal EGCG treatment and Dyrk1a dosage reduction on craniofacial features associated with Down syndrome.

PubMed

McElyea, Samantha D; Starbuck, John M; Tumbleson-Brink, Danika M; Harrington, Emily; Blazek, Joshua D; Ghoneima, Ahmed; Kula, Katherine; Roper, Randall J

2016-11-15

Trisomy 21 (Ts21) affects craniofacial precursors in individuals with Down syndrome (DS). The resultant craniofacial features in all individuals with Ts21 may significantly affect breathing, eating and speaking. Using mouse models of DS, we have traced the origin of DS-associated craniofacial abnormalities to deficiencies in neural crest cell (NCC) craniofacial precursors early in development. Hypothetically, three copies of Dyrk1a (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), a trisomic gene found in most humans with DS and mouse models of DS, may significantly affect craniofacial structure. We hypothesized that we could improve DS-related craniofacial abnormalities in mouse models using a Dyrk1a inhibitor or by normalizing Dyrk1a gene dosage. In vitro and in vivo treatment with Epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, modulated trisomic NCC deficiencies at embryonic time points. Furthermore, prenatal EGCG treatment normalized some craniofacial phenotypes, including cranial vault in adult Ts65Dn mice. Normalization of Dyrk1a copy number in an otherwise trisomic Ts65Dn mice normalized many dimensions of the cranial vault, but did not correct all craniofacial anatomy. These data underscore the complexity of the gene–phenotype relationship in trisomy and suggest that changes in Dyrk1a expression play an important role in morphogenesis and growth of the cranial vault. These results suggest that a temporally specific prenatal therapy may be an effective way to ameliorate some craniofacial anatomical changes associated with DS.

Epigenetically Modified Bone Marrow Stromal Cells in Silk Scaffolds Promote Craniofacial Bone Repair and Wound Healing

PubMed Central

Han, Qianqian; Yang, Pishan; Wu, Yuwei; Meng, Shu; Sui, Lei; Zhang, Lan; Yu, Liming; Tang, Yin; Jiang, Hua; Xuan, Dongying; Kaplan, David L.; Kim, Sung Hoon

2015-01-01

Epigenetic regulation of gene expression is a central mechanism that governs cell stemness, determination, commitment, and differentiation. It has been recently found that PHF8, a major H4K20/H3K9 demethylase, plays a critical role in craniofacial and bone development. In this study, we hypothesize that PHF8 promotes osteoblastogenesis by epigenetically regulating the expression of a nuclear matrix protein, special AT-rich sequence-binding protein 2 (SATB2) that plays pivotal roles in skeletal patterning and osteoblast differentiation. Our results showed that expression levels of PHF8 and SATB2 in preosteoblasts and bone marrow stromal cells (BMSCs) increased simultaneously during osteogenic induction. Overexpressing PHF8 in these cells upregulated the expression of SATB2, Runx2, osterix, and bone matrix proteins. Conversely, knockdown of PHF8 reduced the expression of these genes. Furthermore, ChIP assays confirmed that PHF8 specifically bound to the transcription start site (TSS) of the SATB2 promoter, and the expression of H3K9me1 at the TSS region of SATB2 decreased in PHF8 overexpressed group. Implantation of the BMSCs overexpressing PHF8 with silk protein scaffolds promoted bone regeneration in critical-sized defects in mouse calvaria. Taken together, our results demonstrated that PHF8 epigenetically modulates SATB2 activity, triggering BMSCs osteogenic differentiation and facilitating bone formation and regeneration in biodegradable silk scaffolds. PMID:25923143

Bioactive nano-fibrous scaffold for vascularized craniofacial bone regeneration.

PubMed

Prabha, Rahul Damodaran; Kraft, David Christian Evar; Harkness, Linda; Melsen, Birte; Varma, Harikrishna; Nair, Prabha D; Kjems, Jorgen; Kassem, Moustapha

2018-03-01

There has been a growing demand for bone grafts for correction of bone defects in complicated fractures or tumours in the craniofacial region. Soft flexible membrane like material that could be inserted into defect by less invasive approaches; promote osteoconductivity and act as a barrier to soft tissue in growth while promoting bone formation is an attractive option for this region. Electrospinning has recently emerged as one of the most promising techniques for fabrication of extracellular matrix such as nano-fibrous scaffolds that can serve as a template for bone formation. To overcome the limitation of cell penetration of electrospun scaffolds and improve on its osteoconductive nature, in this study, we fabricated a novel electrospun composite scaffold of polyvinyl alcohol (PVA)-poly (ε) caprolactone (PCL)-Hydroxyapatite based bioceramic (HAB), namely, PVA-PCL-HAB. The scaffold prepared by dual electrospinning of PVA and PCL with HAB overcomes reduced cell attachment associated with hydrophobic PCL by combination with a hydrophilic PVA and the HAB can contribute to enhance osteoconductivity. We characterized the physicochemical and biocompatibility properties of the new scaffold material. Our results indicate PVA-PCL-HAB scaffolds support attachment and growth of stromal stem cells; [human bone marrow skeletal (mesenchymal) stem cells and dental pulp stem cells]. In addition, the scaffold supported in vitro osteogenic differentiation and in vivo vascularized bone formation. Thus, PVA-PCL-HAB scaffold is a suitable potential material for therapeutic bone regeneration in dentistry and orthopaedics. Copyright © 2017 John Wiley & Sons, Ltd.

Essential functions of the Williams-Beuren syndrome-associated TFII-I genes in embryonic development.

PubMed

Enkhmandakh, Badam; Makeyev, Aleksandr V; Erdenechimeg, Lkhamsuren; Ruddle, Frank H; Chimge, Nyam-Osor; Tussie-Luna, Maria Isabel; Roy, Ananda L; Bayarsaihan, Dashzeveg

2009-01-06

GTF2I and GTF2IRD1 encoding the multifunctional transcription factors TFII-I and BEN are clustered at the 7q11.23 region hemizygously deleted in Williams-Beuren syndrome (WBS), a complex multisystemic neurodevelopmental disorder. Although the biochemical properties of TFII-I family transcription factors have been studied in depth, little is known about the specialized contributions of these factors in pathways required for proper embryonic development. Here, we show that homozygous loss of either Gtf2ird1 or Gtf2i function results in multiple phenotypic manifestations, including embryonic lethality; brain hemorrhage; and vasculogenic, craniofacial, and neural tube defects in mice. Further analyses suggest that embryonic lethality may be attributable to defects in yolk sac vasculogenesis and angiogenesis. Microarray data indicate that the Gtf2ird1 homozygous phenotype is mainly caused by an impairment of the genes involved in the TGFbetaRII/Alk1/Smad5 signal transduction pathway. The effect of Gtf2i inactivation on this pathway is less prominent, but downregulation of the endothelial growth factor receptor-2 gene, resulting in the deterioration of vascular signaling, most likely exacerbates the severity of the Gtf2i mutant phenotype. A subset of Gtf2ird1 and Gtf2i heterozygotes displayed microcephaly, retarded growth, and skeletal and craniofacial defects, therefore showing that haploinsufficiency of TFII-I proteins causes various developmental anomalies that are often associated with WBS.

Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

PubMed

Sessle, B J

2000-01-01

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.

Aminocaproic acid administration is associated with reduced perioperative blood loss and transfusion in pediatric craniofacial surgery.

PubMed

Hsu, G; Taylor, J A; Fiadjoe, J E; Vincent, A M; Pruitt, E Y; Bartlett, S P; Stricker, P A

2016-02-01

Severe blood loss is a common complication of craniofacial reconstruction surgery. The antifibrinolytic ε-aminocaproic acid (EACA) reduces transfusion requirements in children undergoing cardiac surgery and in older children undergoing spine surgery. Tranexamic acid (TXA), another antifibrinolytic with a similar mechanism of action, has been shown to reduce blood loss and transfusion requirements in children undergoing craniofacial surgery. However, TXA has been associated with an increase in post-operative seizures and is more expensive than EACA. There is currently little published data evaluating the efficacy of EACA in children undergoing craniofacial surgery. This is a retrospective study of prospectively collected data from our craniofacial perioperative registries for children under 6 years of age who underwent anterior or posterior cranial vault reconstruction. We compared calculated blood loss, blood donor exposures, and post-operative drain output between subjects who received EACA and those who did not. The registry queries returned data from 152 subjects. Eighty-six did not receive EACA and 66 received EACA. The EACA group had significantly lower calculated blood loss (82 ± 43 vs. 106 ± 63 ml/kg, P = 0.01), fewer intraoperative blood donor exposures (median 2, interquartile range 1-2 vs. median 2, interquartile range 1-3; P = 0.02) and lower surgical drain output in the first post-operative 24 h (28 ml/kg vs. 37 ml/kg, P = 0.001) than the non-EACA group. In this analysis of prospectively captured observational data, EACA administration was associated with less calculated blood loss, intraoperative blood donor exposures, and post-operative surgical drain output. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development

PubMed Central

Hernandez, Jose A.; Gonzalez, Cesar G.

2017-01-01

There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms. PMID:28686747

Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development.

PubMed

Sakai, Daisuke; Trainor, Paul A

2016-09-01

One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore, understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However, our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies. © 2016 Japanese Society of Developmental Biologists.

Face off against ROS: Tcof1/Treacle safeguards neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development

PubMed Central

Sakai, Daisuke; Trainor, Paul A.

2016-01-01

One-third of all congenital birth defects affect the head and face, and most craniofacial anomalies are considered to arise through defects in the development of cranial neural crest cells. Cranial neural crest cells give rise to the majority of craniofacial bones, cartilages and connective tissues. Therefore understanding the events that control normal cranial neural crest and subsequent craniofacial development is important for elucidating the pathogenetic mechanisms of craniofacial anomalies and for the exploring potential therapeutic avenues for their prevention. Treacher Collins syndrome (TCS) is a congenital disorder characterized by severe craniofacial anomalies. An animal model of TCS, generated through mutation of Tcof1, the mouse (Mus musculus) homologue of the gene primarily mutated in association with TCS in humans, has recently revealed significant insights into the pathogenesis of TCS. Apoptotic elimination of neuroepithelial cells including neural crest cells is the primary cause of craniofacial defects in Tcof1 mutant embryos. However our understanding of the mechanisms that induce tissue-specific apoptosis remains incomplete. In this review, we describe recent advances in our understanding of the pathogenesis TCS. Furthermore, we discuss the role of Tcof1 in normal embryonic development, the correlation between genetic and environmental factors on the severity of craniofacial abnormalities, and the prospect for prenatal prevention of craniofacial anomalies. PMID:27481486

What difference can a minute make? Social skills and first impressions of youth with craniofacial differences.

PubMed

Edwards, Todd C; Topolski, Tari D; Kapp-Simon, Kathleen A; Aspinall, Cassandra L; Patrick, Donald L

2011-01-01

To determine whether raters' first impressions of youth with craniofacial differences are modifiable. Observational study of the association between first impressions and social skills as related to youth aged 11 to 18 years with craniofacial differences. University research offices and clinics. Youth aged 11 to 18 years with (n  =  29) and without (n  =  31) craniofacial differences; adults (n  =  40), dental/medical students (n  =  46), and education students (n  =  29), all without craniofacial differences. Participants were recruited from medical clinics and through community advertising at all three study sites. The First Impressions Rating Scale. After viewing 1-minute portrayals of positive social skills by actors with craniofacial differences, raters' perceptions moved significantly in the positive direction for all 26 attributes on the First Impressions Rating Scale; whereas, after viewing negative social skills, ratings moved significantly in the negative direction for 25 of 26 First Impressions Rating Scale attributes. It appears that first impressions others have of youth with craniofacial differences are significantly affected by how these youth present themselves in social situations, suggesting that positive social skills may help reduce the amount of stigma that youth with craniofacial differences encounter.

The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery

PubMed Central

Joyce, Cormac W; Thomas, Sangeetha; Concannon, Elizabeth; Murray, Dylan

2015-01-01

Background Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. Methods Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. Results The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. Conclusions This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty. PMID:26430626

The suture provides a niche for mesenchymal stem cells of craniofacial bones

PubMed Central

Zhao, Hu; Feng, Jifan; Ho, Thach-Vu; Grimes, Weston; Urata, Mark; Chai, Yang

2015-01-01

Bone tissue undergoes constant turnover supported by stem cells. Recent studies showed that perivascular mesenchymal stem cells (MSCs) contribute to the turnover of long bones. Craniofacial bones are flat bones derived from a different embryonic origin than the long bones. The identity and regulating niche for craniofacial bone MSCs remain unknown. Here, we identify Gli1+ cells within the suture mesenchyme as the major MSC population for craniofacial bones. They are not associated with vasculature, give rise to all craniofacial bones in the adult and are activated during injury repair. Gli1+ cells are typical MSCs in vitro. Ablation of Gli1+ cells leads to craniosynostosis and arrest of skull growth, indicating these cells are an indispensible stem cell population. Twist1+/− mice with craniosynostosis show reduced Gli1+ MSCs in sutures, suggesting that craniosynostosis may result from diminished suture stem cells. Our study indicates that craniofacial sutures provide a unique niche for MSCs for craniofacial bone homeostasis and repair. PMID:25799059

National Institute of Dental and Craniofacial Research

MedlinePlus

... In Skip to Main Content National Institute of Dental and Craniofacial Research (NIDCR) Improving the Nation's Oral ... Researchers NIDCR Strategic Plan The National Institute of Dental and Craniofacial Research remains committed to improving the ...

Virtual Surgical Planning in Craniofacial Surgery

PubMed Central

Chim, Harvey; Wetjen, Nicholas; Mardini, Samir

2014-01-01

The complex three-dimensional anatomy of the craniofacial skeleton creates a formidable challenge for surgical reconstruction. Advances in computer-aided design and computer-aided manufacturing technology have created increasing applications for virtual surgical planning in craniofacial surgery, such as preoperative planning, fabrication of cutting guides, and stereolithographic models and fabrication of custom implants. In this review, the authors describe current and evolving uses of virtual surgical planning in craniofacial surgery. PMID:25210509

Craniofacial Surgery Fellowship Websites.

PubMed

Silvestre, Jason; Agarwal, Divyansh; Taylor, Jesse A

2016-06-01

Applicants for craniofacial surgery fellowships utilize Internet-based resources like the San Francisco (SF) Match to manage applications. The purpose of this study was to evaluate the accessibility and content of craniofacial surgery fellowship websites (CSFWs). A list of available craniofacial surgery fellowships was compiled from directories of the American Society of Craniofacial Surgery (ACSFS) and SF Match. Accessibility of CSFWs was assessed via links from these directories and a Google search. Craniofacial surgery fellowship websites were evaluated on education and recruitment content and compared via program characteristics. Twenty-four of the 28 US-based craniofacial surgery fellowship programs had a CSFW (86%). The ACSFS and SF Match databases had limited CSFW accessibility, but a Google search revealed most CSFWs had the top search result (76%). In total, CSFWs provided an average of 39% of education and recruitment variables. While most programs provided fellowship program descriptions (96%), application links (96%), and faculty listings (83%), relatively few provided rotation schedules (13%), fellow selection process information (13%), or interview dates (8%). CSFW content did not vary by program location, faculty size, accreditation status, or institutional affiliations (P > 0.05). Craniofacial surgery fellowships often lack readily accessible websites from national program lists and have limited information for interested applicants. The consistent lack of online information across programs suggests future opportunities exist to improve these educational resources.

Understanding Cleft and Craniofacial Team Care

MedlinePlus

... Donor Spotlight Fundraising Ideas Vehicle Donation Volunteer Efforts Cleft Lip/Palate & Craniofacial Specialists in Your Area skip to submenu Who We Are What We Do Cleft Lip/Palate & Craniofacial Specialists in Your Area States: A States: ...

Effects of simultaneous palatal expansion and mandibular advancement in a child suffering from OSA.

PubMed

Galeotti, A; Festa, P; Pavone, M; De Vincentiis, G C

2016-08-01

This clinical report describes a child suffering from obstructive sleep apnoea (OSA) and class II skeletal malocclusion with maxillary contraction and anterior open bite. He presented moderate obstructive sleep apnoea with large impact on quality of life of patient and parents. He was treated using an innovative orthodontic device (Sleep Apnea Twin Expander) to simultaneously carry out palatal expansion and mandibular advancement. After orthodontic therapy, the OSA-18 questionnaire demonstrated an improvement of the main respiratory symptoms, while cardiorespiratory sleep study revealed a reduction in obstructive sleep apnoea events. Post-treatment, clinical assessment and cephalometric analysis showed a reduction of sagittal maxillary discrepancy and an extension of upper airway space. In conclusion, this case report suggests that orthodontic treatment might be a valuable alternative treatment in children with obstructive sleep apnoea related to craniofacial anomalies. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

[Intravenous Sedation and Repeated "the Same Day General Anesthesia" for a School-age Boy with Dandy-Walker Syndrome and Dentinogenesis].

PubMed

Hitosugi, Takashi; Tsukamoto, Masanori; Fujiwara, Shigeki; Yokoyama, Takeshi

2016-03-01

Dandy-Walker syndrome (DWS) is characterized by perfect or partial defect of the cerebellum vermis and cystic dilatation of the posterior fossa communicating with the fourth ventricle. Common clinical signs are mental retardation, cerebellar ataxia, and those of increased intracranial pressure (ICP). Associated congenital anomalies are craniofacial, cardiac, renal, and skeletal abnormalities. We experienced a case of intravenous sedation and six times of "the same day" general anesthesia for a school-aged boy (10-13 years old) with DWS and hypodentinogenesis. The patient underwent an examination and dental treatments. We had to pay attention to airway management tracheal tube selection and control of ICP. In addition, we should prevent tooth injuries through mishaps during tracheal intubations, since all-tooth-hypoplasia with fragile dental crowns was strongly suggested in this case. Detailed postoperative care is also required for general anesthesia afflicted with DWS.

Anatomical appraisal of the skulls and teeth associated with the family of Tsar Nicolay Romanov.

PubMed

Kolesnikov, L L; Pashinyan, G A; Abramov, S S

2001-02-01

This article describes the identification of skeletal remains attributed to the family of Tsar Nicolay Romanov and other persons buried together at a site near present-day Ekaterinburg, Russia. Detailed descriptions are given regarding the objective methods of craniofacial and odontological identification that were used. Employing computer-assisted photographic superimposition techniques and statistical analysis of morphologic and other characteristics of the specimens, this study identifies with a high likelihood of certainty the remains of the Tsar, his wife, three of his four daughters, and four household assistants. Very strong evidence is presented that the Tsar's daughter Anastasia was killed in 1918. This study demonstrates the effectiveness of the methods and trustworthiness of the results, as well as the prospects of future application of the methods for the identification of skeletonized human remains. Anat Rec (New Anat) 265:15-32, 2001. Copyright 2001 Wiley-Liss, Inc.

Craniofacial Characteristics of Thalassemia Major Patients

PubMed Central

Karakas, Sacide; Tellioglu, Ayfer Metin; Bilgin, Mehmet; Omurlu, Imran Kurt; Caliskan, Sercin; Coskun, Salih

2016-01-01

Objective: Thalassemias major are the most common autosomal recessive disorders; they are characterized by anomalies in the synthesis of the beta chains of hemoglobin and are often associated with varying degrees of craniofacial anomalies. The purpose of this study was to evaluate the craniofacial dimensions of β-thalassemia patients and to identify differences by comparing them to those of a control group. Materials and Methods: The study comprised 43 thalassemia major patients and 26 age- and sex- matched healthy control subjects. Anthropometric measurements were performed in six different craniofacial regions (head, face, nose, mouth, eyes, and ears); a total of 23 craniofacial variables were measured. Results: Craniofacial measurements in the regions of the face, nose, lips and mouth, and ears in the thalassemia major patient group yielded statistically significant differences compared to those in the control group (p<0.05). However, no statistically significant differences were observed in the measurements of the head and eye regions. Conclusion: The study increased our understanding of the craniofacial anatomy of thalassemia major patients and enabled us to obtain quantitative results. PMID:28149147

Reconstitution of craniofacial osseous contour deformities, sequelae of trauma and post resection for tumors, with an alloplastic-autogenous graft.

PubMed

Leake, D L; Habal, M B

1977-04-01

Our experience using a new technique for reconstructing contour defects of facial bones has been presented. It employs particulate, cancellous bone and an implantable prosthesis accurately fabricated of polyether urethane and polyethylene terephthalate cloth mesh which can be produced in a variety of configurations. A mannequin made of these materials displaying the various parts of the craniofacial complex that have been restored or are currently under investigation is shown in Figure 10. Large cranial vault defects, orbital floors, mandibles including chin augmentation, and nasal bone deformities have been successfully restored in man. Restoration of the pinna of the ear is currently being evaluated in laboratory animals.

Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function

PubMed Central

Jones, Natalie C; Lynn, Megan L; Gaudenz, Karin; Sakai, Daisuke; Aoto, Kazushi; Rey, Jean-Phillipe; Glynn, Earl F; Ellington, Lacey; Du, Chunying; Dixon, Jill; Dixon, Michael J; Trainor, Paul A

2010-01-01

Treacher Collins syndrome (TCS) is a congenital disorder of craniofacial development arising from mutations in TCOF1, which encodes the nucleolar phosphoprotein Treacle. Haploinsufficiency of Tcof1 perturbs mature ribosome biogenesis, resulting in stabilization of p53 and the cyclin G1–mediated cell-cycle arrest that underpins the specificity of neuroepithelial apoptosis and neural crest cell hypoplasia characteristic of TCS. Here we show that inhibition of p53 prevents cyclin G1–driven apoptotic elimination of neural crest cells while rescuing the craniofacial abnormalities associated with mutations in Tcof1 and extending life span. These improvements, however, occur independently of the effects on ribosome biogenesis; thus suggesting that it is p53-dependent neuroepithelial apoptosis that is the primary mechanism underlying the pathogenesis of TCS. Our work further implies that neuroepithelial and neural crest cells are particularly sensitive to cellular stress during embryogenesis and that suppression of p53 function provides an attractive avenue for possible clinical prevention of TCS craniofacial birth defects and possibly those of other neurocristopathies. PMID:18246078

Soft-tissue volumetric changes following monobloc distraction procedure: analysis using digital three-dimensional photogrammetry system (3dMD).

PubMed

Chan, Fuan Chiang; Kawamoto, Henry K; Federico, Christina; Bradley, James P

2013-03-01

We have previously reported that monobloc advancement by distraction osteogenesis resulted in decreased morbidity and greater advancement with less relapse compared with acute monobloc advancement with bone grafting. In this study, we examine the three-dimensional (3D) volumetric soft-tissue changes in monobloc distraction.Patients with syndromic craniosynostosis who underwent monobloc distraction from 2002 to 2010 at University of California-Los Angeles Craniofacial Center were studied (n = 12). We recorded diagnosis, indications for the surgery, and volumetric changes for skeletal and soft-tissue midface structures (preoperative/postoperative [6 weeks]/follow-up [>1 year]). Computed tomography scans and a digital 3D photogrammetry system were used for image analysis.Patients ranged from 6 to 14 years of age (mean, 10.1 years) at the time of the operation (follow-up 2-11 years); mean distraction advancement was 19.4 mm (range, 14-25 mm). There was a mean increase in the 3D volumetric soft-tissue changes: 99.5 ± 4.0 cm(3) (P < 0.05) at 6 weeks and 94.9 ± 3.6 cm(3) (P < 0.05) at 1-year follow-up. When comparing soft-tissue changes at 6 weeks postoperative to 1-year follow-up, there were minimal relapse changes. The overall mean 3D skeletal change was 108.9 ± 4.2 cm. For every 1 cm of skeletal gain, there was 0.78 cm(3) of soft-tissue gain.Monobloc advancement by distraction osteogenesis using internal devices resulted in increased volumetric soft-tissue changes, which remained stable at 1 year. The positive linear correlation between soft-tissue increments and bony advancement can be incorporated during the planning of osteotomies to achieve optimum surgical outcomes with monobloc distraction.

Histone Deacetylases in Bone Development and Skeletal Disorders

PubMed Central

Bradley, Elizabeth W.; Carpio, Lomeli R.; van Wijnen, Andre J.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.

2015-01-01

Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn2+ for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2+. Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of this knowledge for orthopedic applications and bone tissue engineering. PMID:26378079

Parental dietary seleno-L-methionine exposure and resultant offspring developmental toxicity

PubMed Central

Chernick, Melissa; Ware, Megan; Albright, Elizabeth; Kwok, Kevin W.H.; Dong, Wu; Zheng, Na; Hinton, David E.

2015-01-01

Selenium (Se) leaches into water from agricultural soils and from storage sites for coal fly ash. Se toxicity causes population and community level effects in fishes and birds. We used the laboratory aquarium model fish, Japanese medaka (Oryzias latipes), an asynchronous breeder, to determine aspects of uptake in adults and resultant developmental toxicity in their offspring. The superior imaging properties of the model enabled detailed descriptions of phenotypic alterations not commonly reported in the existing Se literature. Adult males and females in treatment groups were exposed, separately and together, to a dry diet spiked with 0, 12.5, 25, or 50 µg/g (dry weight) seleno-L-methionine (SeMet) for 6 days, and their embryo progeny collected for 5 days, maintained under controlled conditions and observed daily for hatchability, mortality and/or developmental toxicity. Sites of alteration included: craniofacial, pericardium and abdomen (Pc/Ab), notochord, gall bladder, spleen, blood, and swim bladder. Next, adult tissue Se concentrations (liver, skeletal muscle, ovary and testis) were determined and compared in treatment groups of bred and unbred individuals. No significant difference was found across treatment groups at the various SeMet concentrations; and, subsequent analysis compared exposed vs. control in each of the treatment groups at 10 dpf. Increased embryo mortality was observed in all treatment groups, compared to controls, and embryos had a decreased hatching rate when both parents were exposed. Exposure resulted in significantly more total altered phenotypes than controls. When altered phenotypes following exposure of both parents were higher than maternal only exposure, a male role was suggested. The comparisons between treatment groups revealed that particular types of phenotypic change may be driven by the sex of the exposed parent. Additionally, breeding reduced Se concentrations in some adult tissues, specifically the liver of exposed females and skeletal muscle of exposed males. Detailed phenotypic analysis of progeny from SeMet exposed parents should inform investigations of later life stages in an effort to determine consequences of early life exposure. PMID:26655662

Craniofacial orthodontics and postgraduate orthodontic training in Nigeria.

PubMed

Isiekwe, G I; Oguchi, C O; daCosta, O O; Utomi, I L

2016-01-01

Craniofacial orthodontics has been shown to be a critical component of the care of patients with craniofacial anomalies such as cleft lip and palate. Thus, the purpose of this study was to assess the perceptions and clinical experience in cleft and craniofacial care, of orthodontic residents in Nigeria. Questionnaires were sent out to orthodontic residents in the six Postgraduate Orthodontic Training Centers in the country at that time. The questionnaires were self-administered and covered areas in beliefs in cleft care and the clinical experience and challenges faced by the residents in the provision of craniofacial orthodontic care at their various institutions. Thirty-three respondents returned completed questionnaires, with a response rate of 97%. All the respondents believed that residents should be involved in cleft and craniofacial care. Postnatal counseling was the clinical procedure in which the residents reported the highest level of clinical experience (47.4%). The least clinical experience was recorded in pre-bone graft orthodontics (7.4%) and orthodontic preparation for orthognathic surgery (5.5%). Some of the challenges highlighted by the residents were low patients turn out for orthodontic care and the absence of multidisciplinary treatment for craniofacial patients in their centers. Orthodontic residents in Nigeria believe that they should be involved in the management of patients with craniofacial anomalies and cleft lip and palate. However, majority of the residents have limited clinical experience in the management of these patients. A lot more needs to be done, to expose orthodontic residents in training, to all aspects of the orthodontic and multidisciplinary team care required for the cleft/craniofacial patient.

Quantifying Normal Craniofacial Form and Baseline Craniofacial Asymmetry in the Pediatric Population.

PubMed

Cho, Min-Jeong; Hallac, Rami R; Ramesh, Jananie; Seaward, James R; Hermann, Nuno V; Darvann, Tron A; Lipira, Angelo; Kane, Alex A

2018-03-01

Restoring craniofacial symmetry is an important objective in the treatment of many craniofacial conditions. Normal form has been measured using anthropometry, cephalometry, and photography, yet all of these modalities have drawbacks. In this study, the authors define normal pediatric craniofacial form and craniofacial asymmetry using stereophotogrammetric images, which capture a densely sampled set of points on the form. After institutional review board approval, normal, healthy children (n = 533) with no known craniofacial abnormalities were recruited at well-child visits to undergo full head stereophotogrammetric imaging. The children's ages ranged from 0 to 18 years. A symmetric three-dimensional template was registered and scaled to each individual scan using 25 manually placed landmarks. The template was deformed to each subject's three-dimensional scan using a thin-plate spline algorithm and closest point matching. Age-based normal facial models were derived. Mean facial asymmetry and statistical characteristics of the population were calculated. The mean head asymmetry across all pediatric subjects was 1.5 ± 0.5 mm (range, 0.46 to 4.78 mm), and the mean facial asymmetry was 1.2 ± 0.6 mm (range, 0.4 to 5.4 mm). There were no significant differences in the mean head or facial asymmetry with age, sex, or race. Understanding the "normal" form and baseline distribution of asymmetry is an important anthropomorphic foundation. The authors present a method to quantify normal craniofacial form and baseline asymmetry in a large pediatric sample. The authors found that the normal pediatric craniofacial form is asymmetric, and does not change in magnitude with age, sex, or race.

Severe Craniofacial Involvement due to Amniotic Band Sequence.

PubMed

Becerra-Solano, Luis Eduardo; Castañeda-Cisneros, Gema; Corona-Rivera, Jorge Roman; Díaz-Rodríguez, Manuel; Figuera, Luis Eduardo; López-Muñoz, Eunice; Nastasi-Catanese, José Antonio; Toscano-Flores, José Jesús; Ramírez-Dueñas, María de Lourdes; García-Ortíz, José Elias

2018-02-01

Disruptive amniotic band sequence (DABS) is a sporadic, non-familial disorder with unclear etiology. Diagnosis is based on clinical features because there is currently no reliable laboratory diagnostic tests. We describe six cases of DABS with severe craniofacial deformations, three with and three without classical constrictive limb deformation. The craniofacial deformities were delimited by peripheral sharply demarcated scarring. When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS should be considered despite the absence of constrictive limb scarring.

FGFR2c-mediated ERK-MAPK activity regulates coronal suture development

PubMed Central

Pfaff, Miles J.; Xue, Ke; Li, Li; Horowitz, Mark C.; Steinbacher, Derek M.; Eswarakumar, Jacob V.P.

2017-01-01

Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor’s gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. PMID:27034231

Minor physical anomalies and craniofacial measures in patients with treatment-resistant schizophrenia.

PubMed

Lin, A-S; Chang, S-S; Lin, S-H; Peng, Y-C; Hwu, H-G; Chen, W J

2015-07-01

Schizophrenia patients have higher rates of minor physical anomalies (MPAs) than controls, particularly in the craniofacial region; this difference lends support to the neurodevelopmental model of schizophrenia. Whether MPAs are associated with treatment response in schizophrenia remains unknown. The aim of this case-control study was to investigate whether more MPAs and specific quantitative craniofacial features in patients with schizophrenia are associated with operationally defined treatment resistance. A comprehensive scale, consisting of both qualitatively measured MPAs and quantitative measurements of the head and face, was applied in 108 patients with treatment-resistant schizophrenia (TRS) and in 104 non-TRS patients. Treatment resistance was determined according to the criteria proposed by Conley & Kelly (2001; Biological Psychiatry 50, 898-911). Our results revealed that patients with TRS had higher MPA scores in the mouth region than non-TRS patients, and the two groups also differed in four quantitative measurements (facial width, lower facial height, facial height, and length of the philtrum), after controlling for multiple comparisons using the false discovery rate. Among these dysmorphological measurements, three MPA item types (mouth MPA score, facial width, and lower facial height) and earlier disease onset were further demonstrated to have good discriminant validity in distinguishing TRS from non-TRS patients in a multivariable logistic regression analysis, with an area under the curve of 0.84 and a generalized R 2 of 0.32. These findings suggest that certain MPAs and craniofacial features may serve as useful markers for identifying TRS at early stages of the illness.

FGFR2c-mediated ERK-MAPK activity regulates coronal suture development.

PubMed

Pfaff, Miles J; Xue, Ke; Li, Li; Horowitz, Mark C; Steinbacher, Derek M; Eswarakumar, Jacob V P

2016-07-15

Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor's gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK-MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK-MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK-MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK-MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis. Copyright © 2016 Elsevier Inc. All rights reserved.

CBCT in orthodontics: assessment of treatment outcomes and indications for its use

PubMed Central

Nervina, J M

2015-01-01

Since its introduction into dentistry in 1998, CBCT has become increasingly utilized for orthodontic diagnosis, treatment planning and research. The utilization of CBCT for these purposes has been facilitated by the relative advantages of three-dimensional (3D) over two-dimensional radiography. Despite many suggested indications of CBCT, scientific evidence that its utilization improves diagnosis and treatment plans or outcomes has only recently begun to emerge for some of these applications. This article provides a comprehensive and current review of key studies on the applications of CBCT in orthodontic therapy and for research to decipher treatment outcomes and 3D craniofacial anatomy. The current diagnostic and treatment planning indications for CBCT include impacted teeth, cleft lip and palate and skeletal discrepancies requiring surgical intervention. The use of CBCT in these and other situations such as root resorption, supernumerary teeth, temporomandibular joint (TMJ) pathology, asymmetries and alveolar boundary conditions should be justified on the basis of the merits relative to risks of imaging. CBCT has also been used to assess 3D craniofacial anatomy in health and disease and of treatment outcomes including that of root morphology and angulation; alveolar boundary conditions; maxillary transverse dimensions and maxillary expansion; airway morphology, vertical malocclusion and obstructive sleep apnoea; TMJ morphology and pathology contributing to malocclusion; and temporary anchorage devices. Finally, this article utilizes findings of these studies and current voids in knowledge to provide ideas for future research that could be beneficial for further optimizing the use of CBCT in research and the clinical practice of orthodontics. PMID:25358833

Antimicrobial surfaces for craniofacial implants: state of the art.

PubMed

Actis, Lisa; Gaviria, Laura; Guda, Teja; Ong, Joo L

2013-04-01

In an attempt to regain function and aesthetics in the craniofacial region, different biomaterials, including titanium, hydroxyapatite, biodegradable polymers and composites, have been widely used as a result of the loss of craniofacial bone. Although these materials presented favorable success rates, osseointegration and antibacterial properties are often hard to achieve. Although bone-implant interactions are highly dependent on the implant's surface characteristics, infections following traumatic craniofacial injuries are common. As such, poor osseointegration and infections are two of the many causes of implant failure. Further, as increasingly complex dental repairs are attempted, the likelihood of infection in these implants has also been on the rise. For these reasons, the treatment of craniofacial bone defects and dental repairs for long-term success remains a challenge. Various approaches to reduce the rate of infection and improve osseointegration have been investigated. Furthermore, recent and planned tissue engineering developments are aimed at improving the implants' physical and biological properties by improving their surfaces in order to develop craniofacial bone substitutes that will restore, maintain and improve tissue function. In this review, the commonly used biomaterials for craniofacial bone restoration and dental repair, as well as surface modification techniques, antibacterial surfaces and coatings are discussed.

Exploring the Medical and Psychosocial Concerns of Adolescents and Young Adults With Craniofacial Microsomia: A Qualitative Study.

PubMed

Hamilton, Kayla V; Ormond, Kelly E; Moscarello, Tia; Bruce, Janine S; Bereknyei Merrell, Sylvia; Chang, Kay W; Bernstein, Jonathan A

2018-01-01

This study explores the experiences of adolescents and young adults with craniofacial microsomia, including the impact of growing up with this craniofacial condition on daily life and sense of self. The results may guide future research on optimally supporting individuals with craniofacial microsomia during this critical life phase. Participants were recruited through a craniofacial center, online patient support groups, and social media sites. Eleven individual semistructured interviews with participants between 12 and 22 years old were conducted by a single interviewer, transcribed, iteratively coded, and thematically analyzed. Five themes were evident in the data: (1) impact on personal growth and character development, (2) negative psychosocial impact, (3) deciding to hide or reveal the condition, (4) desire to make personal surgical decisions, and (5) struggles with hearing loss. We identified both medical and psychosocial concerns prevalent among adolescents with craniofacial microsomia. Although adolescents with craniofacial microsomia exhibit considerable resilience, the challenges they face impact their sense of self and should be addressed through psychosocial support and counseling. Further research should investigate the potential benefit of the wider use of hearing aids, as well as the involvement of patients in decision-making about reconstructive ear surgery.

Adult psychological functioning of individuals born with craniofacial anomalies.

PubMed

Sarwer, D B; Bartlett, S P; Whitaker, L A; Paige, K T; Pertschuk, M J; Wadden, T A

1999-02-01

This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.

Anteverted internal auditory canal as an inner ear anomaly in patients with craniofacial microsomia.

PubMed

L'Heureux-Lebeau, Bénédicte; Saliba, Issam

2014-09-01

Craniofacial microsomia involves structure of the first and second branchial arches. A wide range of ear anomalies, affecting external, middle and inner ear, has been described in association with this condition. We report three cases of anteverted internal auditory canal in patients presenting craniofacial microsomia. This unique internal auditory canal orientation was found on high-resolution computed tomography of the temporal bones. This internal auditory canal anomaly is yet unreported in craniofacial anomalies. Copyright © 2014. Published by Elsevier Ireland Ltd.

Proteoliposomes as matrix vesicles’ biomimetics to study the initiation of skeletal mineralization

PubMed Central

Simão, A.M.S.; Yadav, M.C.; Ciancaglini, P.; Millán, J.L.

2017-01-01

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Ion transporters control the availability of phosphate and calcium needed for HA deposition. The lipidic microenvironment in which MV-associated enzymes and transporters function plays a crucial physiological role and must be taken into account when attempting to elucidate their interplay during the initiation of biomineralization. In this short mini-review, we discuss the potential use of proteoliposome systems as chondrocyte- and osteoblast-derived MVs biomimetics, as a means of reconstituting a phospholipid microenvironment in a manner that recapitulates the native functional MV microenvironment. Such a system can be used to elucidate the interplay of MV enzymes during catalysis of biomineralization substrates and in modulating in vitro calcification. As such, the enzymatic defects associated with disease-causing mutations in MV enzymes could be studied in an artificial vesicular environment that better mimics their in vivo biological milieu. These artificial systems could also be used for the screening of small molecule compounds able to modulate the activity of MV enzymes for potential therapeutic uses. Such a nanovesicular system could also prove useful for the repair/treatment of craniofacial and other skeletal defects and to facilitate the mineralization of titanium-based tooth implants. PMID:20401430

Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization.

PubMed

Simão, A M S; Yadav, M C; Ciancaglini, P; Millán, J L

2010-03-01

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Ion transporters control the availability of phosphate and calcium needed for HA deposition. The lipidic microenvironment in which MV-associated enzymes and transporters function plays a crucial physiological role and must be taken into account when attempting to elucidate their interplay during the initiation of biomineralization. In this short mini-review, we discuss the potential use of proteoliposome systems as chondrocyte- and osteoblast-derived MVs biomimetics, as a means of reconstituting a phospholipid microenvironment in a manner that recapitulates the native functional MV microenvironment. Such a system can be used to elucidate the interplay of MV enzymes during catalysis of biomineralization substrates and in modulating in vitro calcification. As such, the enzymatic defects associated with disease-causing mutations in MV enzymes could be studied in an artificial vesicular environment that better mimics their in vivo biological milieu. These artificial systems could also be used for the screening of small molecule compounds able to modulate the activity of MV enzymes for potential therapeutic uses. Such a nanovesicular system could also prove useful for the repair/treatment of craniofacial and other skeletal defects and to facilitate the mineralization of titanium-based tooth implants.

Esco2 regulates cx43 expression during skeletal regeneration in the zebrafish fin.

PubMed

Banerji, Rajeswari; Eble, Diane M; Iovine, M Kathryn; Skibbens, Robert V

2016-01-01

Roberts syndrome (RBS) is a rare genetic disorder characterized by craniofacial abnormalities, limb malformation, and often severe mental retardation. RBS arises from mutations in ESCO2 that encodes an acetyltransferase and modifies the cohesin subunit SMC3. Mutations in SCC2/NIPBL (encodes a cohesin loader), SMC3 or other cohesin genes (SMC1, RAD21/MCD1) give rise to a related developmental malady termed Cornelia de Lange syndrome (CdLS). RBS and CdLS exhibit overlapping phenotypes, but RBS is thought to arise through mitotic failure and limited progenitor cell proliferation while CdLS arises through transcriptional dysregulation. Here, we use the zebrafish regenerating fin model to test the mechanism through which RBS-type phenotypes arise. esco2 is up-regulated during fin regeneration and specifically within the blastema. esco2 knockdown adversely affects both tissue and bone growth in regenerating fins-consistent with a role in skeletal morphogenesis. esco2-knockdown significantly diminishes cx43/gja1 expression which encodes the gap junction connexin subunit required for cell-cell communication. cx43 mutations cause the short fin (sof(b123) ) phenotype in zebrafish and oculodentodigital dysplasia (ODDD) in humans. Importantly, miR-133-dependent cx43 overexpression rescues esco2-dependent growth defects. These results conceptually link ODDD to cohesinopathies and provide evidence that ESCO2 may play a transcriptional role critical for human development. © 2015 Wiley Periodicals, Inc.

Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence.

PubMed

Hsu, Wei-Shun; Tsai, Min-Huan; Barve, Indrajeet J; Yellol, Gorakh S; Sun, Chung-Ming

2017-07-10

A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with α-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles under microwave irradiation. Two nonequivalent nucleophilic centers on benzimidazole moiety were manipulated elegantly by different reaction conditions to achieve the skeletal diversity.

76 FR 38193 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia.

PubMed

Yamanaka, S; Nakao, Kazumasa; Koyama, N; Isobe, Y; Ueda, Y; Kanai, Y; Kondo, E; Fujii, T; Miura, M; Yasoda, A; Nakao, Kazuwa; Bessho, K

2017-12-01

Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3 ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3 ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3 ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3 ach /SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3 ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3 ach mice was significantly ameliorated in Fgfr3 ach /SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic potential of CNP for treatment of midfacial hypoplasia and foramen magnum stenosis in achondroplasia.

Tissue–selective effects of nucleolar stress and rDNA damage in developmental disorders

PubMed Central

Calo, Eliezer; Gu, Bo; Bowen, Margot E.; Aryan, Fardin; Zalc, Antoine; Liang, Jialiang; Flynn, Ryan A.; Swigut, Tomek; Chang, Howard Y.; Attardi, Laura D.; Wysocka, Joanna

2018-01-01

Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis1,2. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis3,4, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis5, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Taken together, our findings illustrate how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations. PMID:29364875

Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.

PubMed

Calo, Eliezer; Gu, Bo; Bowen, Margot E; Aryan, Fardin; Zalc, Antoine; Liang, Jialiang; Flynn, Ryan A; Swigut, Tomek; Chang, Howard Y; Attardi, Laura D; Wysocka, Joanna

2018-02-01

Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Taken together, our findings illustrate how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations.

Study on the performance of different craniofacial superimposition approaches (II): Best practices proposal.

PubMed

Damas, S; Wilkinson, C; Kahana, T; Veselovskaya, E; Abramov, A; Jankauskas, R; Jayaprakash, P T; Ruiz, E; Navarro, F; Huete, M I; Cunha, E; Cavalli, F; Clement, J; Lestón, P; Molinero, F; Briers, T; Viegas, F; Imaizumi, K; Humpire, D; Ibáñez, O

2015-12-01

Craniofacial superimposition, although existing for one century, is still a controversial technique within the scientific community. Objective and unbiased validation studies over a significant number of cases are required to establish a more solid picture on the reliability. However, there is lack of protocols and standards in the application of the technique leading to contradictory information concerning reliability. Instead of following a uniform methodology, every expert tends to apply his own approach to the problem, based on the available technology and deep knowledge on human craniofacial anatomy, soft tissues, and their relationships. The aim of this study was to assess the reliability of different craniofacial superimposition methodologies and the corresponding technical approaches to this type of identification. With all the data generated, some of the most representative experts in craniofacial identification joined in a discussion intended to identify and agree on the most important issues that have to be considered to properly employ the craniofacial superimposition technique. As a consequence, the consortium has produced the current manuscript, which can be considered the first standard in the field; including good and bad practices, sources of error and uncertainties, technological requirements and desirable features, and finally a common scale for the craniofacial matching evaluation. Such a document is intended to be part of a more complete framework for craniofacial superimposition, to be developed during the FP7-founded project MEPROCS, which will favour and standardize its proper application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis.

PubMed

Brock, Malcolm; Chung, Tae Hwan; Gaddam, Sathvika Reddy; Kathait, Anjaneya Singh; Ober, Cecily; Georgiades, Christos

2016-12-01

Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia. Primary hyperhidrosis is also thought to be the result of sympathetic dysregulation. We present the case of a patient treated with CT-guided, percutaneous T2 EtOH sympatholysis for craniofacial hyperhidrosis. The patient also suffered from postural orthostatic tachycardia syndrome for many years and was unresponsive to treatment. Immediately after sympatholysis, the patient experienced resolution of both craniofacial hyperhidrosis and postural orthostatic tachycardia syndrome.

Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brock, Malcolm, E-mail: mabrock@jhmni.edu; Chung, Tae Hwan, E-mail: Tchang7@jhmi.edu; Gaddam, Sathvika Reddy, E-mail: drsathvikareddy@yahoo.com

Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia. Primary hyperhidrosis is also thought to be the result of sympathetic dysregulation. We present the case of a patient treated with CT-guided, percutaneous T2 EtOH sympatholysis for craniofacial hyperhidrosis. The patient also suffered from postural orthostatic tachycardia syndrome for many years and was unresponsive to treatment. Immediately after sympatholysis, the patient experiencedmore » resolution of both craniofacial hyperhidrosis and postural orthostatic tachycardia syndrome.« less

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The society for craniofacial genetics and developmental biology 38th annual meeting.

PubMed

Taneyhill, Lisa A; Hoover-Fong, Julie; Lozanoff, Scott; Marcucio, Ralph; Richtsmeier, Joan T; Trainor, Paul A

2016-07-01

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, post doctoral researchers, clinicians, orthodontists, scientists, and academicians who share an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Orthognathic Surgery in Craniofacial Microsomia: Treatment Algorithm

PubMed Central

Valladares, Salvador; Torrealba, Ramón; Nuñez, Marcelo; Uribe, Francisca

2015-01-01

Summary: Craniofacial microsomia is a broad term that covers a variety of craniofacial malformation conditions that are caused by alterations in the derivatives of the first and second pharyngeal arches. In general terms, diverse therapeutic alternatives are proposed according to the growth stage and the severity of the alteration. When craniofacial growth has concluded, conventional orthognathic surgery (Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty) provides good alternatives for MI and MIIA type cases. Reconstruction of the mandibular ramus and temporomandibular joint before orthognathic surgery is the indicated treatment for cases MIIB and MIII. The goal of this article is to establish a surgical treatment algorithm for orthognathic surgery on patients with craniofacial microsomia, analyzing the points that allow the ideal treatment for each patient to be chosen. PMID:25674375

Craniofacial and Dental Development in Costello Syndrome

PubMed Central

Goodwin, Alice F.; Oberoi, Snehlata; Landan, Maya; Charles, Cyril; Massie, Jessica C.; Fairley, Cecilia; Rauen, Katherine A.; Klein, Ophir D.

2014-01-01

Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n=41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development. PMID:24668879

Partial craniofacial duplication: a review of the literature and case report.

PubMed

Costa, Melinda A; Borzabadi-Farahani, Ali; Lara-Sanchez, Pedro A; Schweitzer, Daniela; Jacobson, Lia; Clarke, Noreen; Hammoudeh, Jeffery; Urata, Mark M; Magee, William P

2014-06-01

Diprosopus (Greek; di-, "two" + prosopon, "face"), or craniofacial duplication, is a rare craniofacial anomaly referring to the complete duplication of facial structures. Partial craniofacial duplication describes a broad spectrum of congenital anomalies, including duplications of the oral cavity. This paper describes a 15 month-old female with a duplicated oral cavity, mandible, and maxilla. A Tessier type 7 cleft, midline meningocele, and duplicated hypophysis were also present. The preoperative evaluation, surgical approach, postoperative results, and a review of the literature are presented. The surgical approach was designed to preserve facial nerve innervation to the reconstructed cheek and mouth. The duplicated mandible and maxilla were excised and the remaining left maxilla was bone grafted. Soft tissue repair included closure of the Tessier type VII cleft. Craniofacial duplication remains a rare entity that is more common in females. The pathophysiology remains incompletely characterized, but is postulated to be due to duplication of the notochord, as well as duplication of mandibular growth centres. While diprosopus is a severe deformity often associated with anencephaly, patients with partial duplication typically benefit from surgical treatment. Managing craniofacial duplication requires a detailed preoperative evaluation as well as a comprehensive, staged treatment plan. Long-term follow up is needed appropriately to address ongoing craniofacial deformity. Published by Elsevier Ltd.

Craniofacial and dental development in Costello syndrome.

PubMed

Goodwin, Alice F; Oberoi, Snehlata; Landan, Maya; Charles, Cyril; Massie, Jessica C; Fairley, Cecilia; Rauen, Katherine A; Klein, Ophir D

2014-06-01

Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac, musculoskeletal, dermatological, and developmental abnormalities. The RASopathies are defined as a group of syndromes caused by activated Ras/mitogen-activated protein kinase (MAPK) signaling. Specifically, CS is caused by activating mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental development, the craniofacial and dental features of CS have not been systematically defined in a large group of individuals. In order to address this gap in our understanding and fully characterize the CS phenotype, we evaluated the craniofacial and dental phenotype in a large cohort (n = 41) of CS individuals. We confirmed that the craniofacial features common in CS include macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large mouth. Additionally, CS patients have a characteristic dental phenotype that includes malocclusion with anterior open bite and posterior crossbite, enamel hypo-mineralization, delayed tooth development and eruption, gingival hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the craniofacial and dental phenotype in CS with other RASopathies, such as cardio-facio-cutaneous syndrome (CFC), provides insight into the complexities of Ras/MAPK signaling in human craniofacial and dental development. © 2014 Wiley Periodicals, Inc.

The fusion of craniofacial reconstruction and microsurgery: a functional and aesthetic approach.

PubMed

Broyles, Justin M; Abt, Nicholas B; Shridharani, Sachin M; Bojovic, Branko; Rodriguez, Eduardo D; Dorafshar, Amir H

2014-10-01

Reconstruction of large, composite defects in the craniofacial region has evolved significantly over the past half century. During this time, there have been significant advances in craniofacial and microsurgical surgery. These contributions have often been in parallel; however, over the past 10 years, these two disciplines have begun to overlap more frequently, and the techniques of one have been used to advance the other. In the current review, the authors aim to describe the available options for free tissue reconstruction in craniofacial surgery. A review of microsurgical reconstructive options of aesthetic units within the craniofacial region was undertaken with attention directed toward surgeon flap preference. Anatomical areas analyzed included scalp, calvaria, forehead, frontal sinus, nose, maxilla and midface, periorbita, mandible, lip, and tongue. Although certain flaps such as the ulnar forearm flap and lateral circumflex femoral artery-based flaps were used in multiple reconstructive sites, each anatomical location possesses a unique array of flaps to maximize outcomes. Craniofacial surgery, like plastic surgery, has made tremendous advancements in the past 40 years. With innovations in technology, flap design, and training, microsurgery has become safer, faster, and more commonplace than at any time in history. Reconstructive microsurgery allows the surgeon to be creative in this approach, and free tissue transfer has become a mainstay of modern craniofacial reconstruction.

Rare bone diseases and their dental, oral, and craniofacial manifestations.

PubMed

Foster, B L; Ramnitz, M S; Gafni, R I; Burke, A B; Boyce, A M; Lee, J S; Wright, J T; Akintoye, S O; Somerman, M J; Collins, M T

2014-07-01

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. © International & American Associations for Dental Research.

Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

PubMed Central

Foster, B.L.; Ramnitz, M.S.; Gafni, R.I.; Burke, A.B.; Boyce, A.M.; Lee, J.S.; Wright, J.T.; Akintoye, S.O.; Somerman, M.J.; Collins, M.T.

2014-01-01

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. PMID:24700690

Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

PubMed

Sharples, Adam P; Stewart, Claire E; Seaborne, Robert A

2016-08-01

Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

30-year International Pediatric Craniofacial Surgery Partnership: Evolution from the “Third World” Forward

PubMed Central

Swanson, Jordan W.; Skirpan, Jan; Stanek, Beata; Kowalczyk, Maciej

2016-01-01

Background: Craniofacial diseases constitute an important component of the surgical disease burden in low- and middle-income countries. The consideration to introduce craniofacial surgery into such settings poses different questions, risks, and challenges compared with cleft or other forms of plastic surgery. We report the evolution, innovations, and challenges of a 30-year international craniofacial surgery partnership. Methods: We retrospectively report a partnership between surgeons at the Uniwersytecki Szpital Dzieciecy in Krakow, Poland, and a North American craniofacial surgeon. We studied patient conditions, treatment patterns, and associated complications, as well as program advancements and limitations as perceived by surgeons, patient families, and hospital administrators. Results: Since partnership inception in 1986, the complexity of cases performed increased gradually, with the first intracranial case performed in 1995. In the most recent 10-year period (2006–2015), 85 patients have been evaluated, with most common diagnoses of Apert syndrome, Crouzon syndrome, and single-suture craniosynostosis. In the same period, 55 major surgical procedures have been undertaken, with LeFort III midface distraction, posterior vault distraction, and frontoorbital advancement performed most frequently. Key innovations have been the employment of craniofacial distraction osteogenesis, the use of Internet communication and digital photography, and increased understanding of how craniofacial morphology may improve in the absence of surgical intervention. Ongoing challenges include prohibitive training pathways for pediatric plastic surgeons, difficulty in coordinating care with surgeons in other institutions, and limited medical and material resources. Conclusion: Safe craniofacial surgery can be introduced and sustained in a resource-limited setting through an international partnership. PMID:27200233

75 FR 82033 - National Institute of Dental and Craniofacial Research; Notice of Meeting

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2010-12-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... Dental and Craniofacial Research Council. The meeting will be open to the public as indicated below, with... Committee: National Advisory Dental and Craniofacial Research Council. Date: January 24, 2011. Open: 8:30 a...

78 FR 65348 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

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2013-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Dental and Craniofacial Research Special Emphasis Panel, October 21, 2013, 9:00 a.m...

75 FR 55592 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

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2010-09-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Advisory Dental and Craniofacial Research Council, September 27, 2010, 8:30 a.m. to September 27...

78 FR 65343 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Dental and Craniofacial Research Special Emphasis Panel, October 7, 2013, 10:00 a.m...

Zebrafish Craniofacial Development: A Window into Early Patterning

PubMed Central

Mork, Lindsey; Crump, Gage

2016-01-01

The formation of the face and skull involves a complex series of developmental events mediated by cells derived from the neural crest, endoderm, mesoderm, and ectoderm. Although vertebrates boast an enormous diversity of adult facial morphologies, the fundamental signaling pathways and cellular events that sculpt the nascent craniofacial skeleton in the embryo have proven to be highly conserved from fish to man. The zebrafish Danio rerio, a small freshwater cyprinid fish from eastern India, has served as a popular model of craniofacial development since the 1990s. Unique strengths of the zebrafish model include a simplified skeleton during larval stages, access to rapidly developing embryos for live imaging, and amenability to transgenesis and complex genetics. In this chapter, we describe the anatomy of the zebrafish craniofacial skeleton; its applications as models for the mammalian jaw, middle ear, palate, and cranial sutures; the superior imaging technology available in fish that has provided unprecedented insights into the dynamics of facial morphogenesis; the use of the zebrafish to decipher the genetic underpinnings of craniofacial biology; and finally a glimpse into the most promising future applications of zebrafish craniofacial research. PMID:26589928

The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival

PubMed Central

Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J.

2016-01-01

Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh), a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible). PMID:29615588

The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.

PubMed

Dworkin, Sebastian; Boglev, Yeliz; Owens, Harley; Goldie, Stephen J

2016-08-03

Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog ( Shh ), a vertebrate orthologue of Drosophila hedgehog , is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).

Involuntary craniofacial lingual movements in intensive care-acquired quadriplegia.

PubMed

Cartagena, A M; Jog, M; Young, G B

2012-02-01

The syndrome of involuntary craniofacial lingual movements in the setting of acute intensive care-acquired quadriplegia (critical illness neuromyopathy) following sepsis-associated encephalopathy has not been previously described. We suggest a localization and treatment for this disabling condition. Three patients (2 female) from our center were quadriplegic from critical illness neuromyopathy when they developed involuntary craniofacial lingual movements following sepsis-associated encephalopathy. Extensive investigations failed to identify an etiology for the abnormal movements. Movements were of large amplitude, of moderate speed, and semi-rhythmic in the jaw, tongue, and palate, persistent and extremely bothersome to all patients. Injection with Botulinum toxin type A was very beneficial. Involuntary craniofacial lingual movements in the setting of flaccid quadriplegia following sepsis-associated encephalopathy are consistent with focal craniofacial brainstem myoclonus and constitutes a new syndrome. Botulinum toxin type A treatment maybe helpful in treatment.

A comprehensive analysis of craniofacial trauma.

PubMed

Hussain, K; Wijetunge, D B; Grubnic, S; Jackson, I T

1994-01-01

A review of the literature identified a need for a prospective study of the complete range of craniofacial trauma. The aims of this study were to determine the incidence, etiology, and mechanisms of craniofacial and associated injuries, enabling a greater understanding of their range and magnitude. Nine hundred fifty consecutive patients seen at an urban university hospital with any degree of craniofacial trauma were prospectively investigated. Craniofacial trauma was found to be very common at all ages. The causes were directly related to age, sex, and alcohol consumption, and determine the type and severity of injury. The commonest cause of soft-tissue injury was falls, whereas that of fractures was interpersonal violence. Falls accounted for most of the injuries in children and the elderly, whereas interpersonal violence was mainly responsible for those occurring in patients aged 15 to 50 years. Interpersonal violence mostly involved young male adults: fights occurring mainly between strangers who had consumed excessive amounts of alcohol. Women were usually assaulted by assailants known to them, their partners. Pedestrians showed a propensity to sustain cranial fractures, whereas motor vehicle occupants tended to sustain midfacial fractures and bicyclists mandibular fractures. Pedestrians incurred the severest injuries of all road users, and a significant proportion of road user collisions involved bicyclists. Sports were responsible for a significant proportion of craniofacial injuries in youths and young adults. Craniofacial soft-tissue injuries overall occurred most frequently on the forehead, nose, lips, and chin, and a method for their classification is proposed. The commonest craniofacial fracture was that of the nasal bones (45%), followed by cranial bones (24%), mandible (13%), zygoma (13%), orbital blow-out (3%), and maxilla (2%). The incidence of craniofacial trauma can be greatly reduced by improvements in interior home design, school education in alcohol abuse and handling potentially hostile situations (especially for men), improvement in automotive safety devices and compliance by motor vehicle occupants, and utilization of full-face helmets by bicyclists and motorcyclists.

Interactive effects of temperature, food and skeletal mineralogy mediate biological responses to ocean acidification in a widely distributed bryozoan.

PubMed

Swezey, Daniel S; Bean, Jessica R; Ninokawa, Aaron T; Hill, Tessa M; Gaylord, Brian; Sanford, Eric

2017-04-26

Marine invertebrates with skeletons made of high-magnesium calcite may be especially susceptible to ocean acidification (OA) due to the elevated solubility of this form of calcium carbonate. However, skeletal composition can vary plastically within some species, and it is largely unknown how concurrent changes in multiple oceanographic parameters will interact to affect skeletal mineralogy, growth and vulnerability to future OA. We explored these interactive effects by culturing genetic clones of the bryozoan Jellyella tuberculata (formerly Membranipora tuberculata ) under factorial combinations of dissolved carbon dioxide (CO 2 ), temperature and food concentrations. High CO 2 and cold temperature induced degeneration of zooids in colonies. However, colonies still maintained high growth efficiencies under these adverse conditions, indicating a compensatory trade-off whereby colonies degenerate more zooids under stress, redirecting energy to the growth and maintenance of new zooids. Low-food concentration and elevated temperatures also had interactive effects on skeletal mineralogy, resulting in skeletal calcite with higher concentrations of magnesium, which readily dissolved under high CO 2 For taxa that weakly regulate skeletal magnesium concentration, skeletal dissolution may be a more widespread phenomenon than is currently documented and is a growing concern as oceans continue to warm and acidify. © 2017 The Author(s).

Interactive effects of temperature, food and skeletal mineralogy mediate biological responses to ocean acidification in a widely distributed bryozoan

PubMed Central

Bean, Jessica R.; Ninokawa, Aaron T.; Hill, Tessa M.; Gaylord, Brian; Sanford, Eric

2017-01-01

Marine invertebrates with skeletons made of high-magnesium calcite may be especially susceptible to ocean acidification (OA) due to the elevated solubility of this form of calcium carbonate. However, skeletal composition can vary plastically within some species, and it is largely unknown how concurrent changes in multiple oceanographic parameters will interact to affect skeletal mineralogy, growth and vulnerability to future OA. We explored these interactive effects by culturing genetic clones of the bryozoan Jellyella tuberculata (formerly Membranipora tuberculata) under factorial combinations of dissolved carbon dioxide (CO2), temperature and food concentrations. High CO2 and cold temperature induced degeneration of zooids in colonies. However, colonies still maintained high growth efficiencies under these adverse conditions, indicating a compensatory trade-off whereby colonies degenerate more zooids under stress, redirecting energy to the growth and maintenance of new zooids. Low-food concentration and elevated temperatures also had interactive effects on skeletal mineralogy, resulting in skeletal calcite with higher concentrations of magnesium, which readily dissolved under high CO2. For taxa that weakly regulate skeletal magnesium concentration, skeletal dissolution may be a more widespread phenomenon than is currently documented and is a growing concern as oceans continue to warm and acidify. PMID:28424343

Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors

PubMed Central

Qian, Guofeng; Karnati, Srikanth; Baumgart-Vogt, Eveline

2015-01-01

Ossification defects leading to craniofacial dysmorphism or rhizomelia are typical phenotypes in patients and corresponding knockout mouse models with distinct peroxisomal disorders. Despite these obvious skeletal pathologies, to date no careful analysis exists on the distribution and function of peroxisomes in skeletal tissues and their alterations during ossification. Therefore, we analyzed the peroxisomal compartment in different cell types of mouse cartilage and bone as well as in primary cultures of calvarial osteoblasts. The peroxisome number and metabolism strongly increased in chondrocytes during endochondral ossification from the reserve to the hypertrophic zone, whereas in bone, metabolically active osteoblasts contained a higher numerical abundance of this organelle than osteocytes. The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11β gene expression. During culture, calvarial pre-osteoblasts differentiated into secretory osteoblasts accompanied by peroxisome proliferation and increased levels of peroxisomal genes and proteins. Since many peroxisomal genes contain a PPAR-responsive element, we analyzed the gene expression of PPARɑ/ß/ɣ in calvarial osteoblasts and MC3T3-E1 cells, revealing higher levels for PPARß than for PPARɑ and PPARɣ. Treatment with different PPAR agonists and antagonists not only changed the peroxisomal compartment and associated gene expression, but also induced complex alterations of the gene expression patterns of the other PPAR family members. Studies in M3CT3-E1 cells showed that the PPARß agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat), whereas the PPARß antagonist GSK0660 led to repression of the PPRE and a decrease of the corresponding mRNA levels. In the same way, treatment of calvarial osteoblasts with GW0742 increased in peroxisome number and related gene expression and accelerated osteoblast differentiation. Taken together, our results suggest that PPARß regulates the numerical abundance and metabolic function of peroxisomes via Pex11ß in parallel to osteoblast differentiation. PMID:26630504

Contribution of jaw muscle size and craniofacial morphology to human bite force magnitude.

PubMed

Raadsheer, M C; van Eijden, T M; van Ginkel, F C; Prahl-Andersen, B

1999-01-01

The existence of an interaction among bite force magnitude, jaw muscle size (e.g., cross-sectional area, thickness), and craniofacial morphology is widely accepted. Bite force magnitude depends on the size of the jaw muscles and the lever arm lengths of bite force and muscle forces, which in turn are dictated by craniofacial morphology. In this study, the relative contributions of craniofacial morphology and jaw muscle thickness to the bite force magnitude were studied. In 121 adult individuals, both magnitude and direction of the maximal voluntary bite force were registered. Craniofacial dimensions were measured by anthropometrics and from lateral radiographs. The thicknesses of the masseter, temporal, and digastric muscles were registered by ultrasonography. After a factor analysis was applied to the anthropometric and cephalometric dimensions, the correlation between bite force magnitude, on the one hand, and the "craniofacial factors" and jaw muscle thicknesses, on the other, was assessed by stepwise multiple regression. Fifty-eight percent of the bite force variance could be explained. From the jaw muscles, only the thickness of the masseter muscle correlated significantly with bite force magnitude. Bite force magnitude also correlated significantly positively with vertical and transverse facial dimensions and the inclination of the midface, and significantly negatively with mandibular inclination and occlusal plane inclination. The contribution of the masseter muscle to the variation in bite force magnitude was higher than that of the craniofacial factors.

Biomaterials and biologics in craniofacial reconstruction.

PubMed

Engstrand, Thomas

2012-01-01

Complications related to surgery, including infection, wound dehiscence, and implant protrusion, are costly and may cause severe morbidity to patients. The choice of implants materials is critical for a successful outcome, particularly in craniofacial reconstructions. This review discusses the potential benefits and drawbacks of biologically active materials used for craniofacial bone repair as alternatives to inert implant prostheses.

Analysis of an In-Service Examination for Core Pediatric Craniofacial Surgery Knowledge.

PubMed

Silvestre, Jason; Chang, Benjamin; Taylor, Jesse A

2016-01-01

Little is known about designing an effective residency curriculum for pediatric craniofacial surgery. This study elucidates the pediatric craniofacial curriculum of the Plastic Surgery In-Service Training Examination (PSITE) to facilitate knowledge acquisition during residency. Approximately, 6 consecutive PSITEs were reviewed for pediatric craniofacial questions (2010-2015). Subjects were categorized according to topics on the American Board of Plastic Surgery written board examination. Questions were categorized using an educational taxonomy model. Answer references were categorized by source and publication lag. Of 1174 PSITE questions, 147 tested pediatric craniofacial topics (12.5%). Questions appeared predominately in the Craniomaxillofacial section (83.0%, p < 0.001). The annual representation was stable more than 6 years (range: 10.2%-14.4%, p = 0.842). Question taxonomy favored interpretation (45.6%) and decision-making (40.8%) over recall (13.6%, p < 0.001) skills, and 41 questions had an associated image (27.9%) and most were photographic (76.7%, p < 0.001). The most frequently tested categories on the American Board of Plastic Surgery written examination content outline were craniofacial anomalies (23.5%), benign and malignant tumors (17.6%), and cleft lip and palate (12.5%). Overall, 80 unique journals were cited 304 times with a mean publication lag of 9.4 ± 10.9 years. Plastic and Reconstructive Surgery (34.5%) was the most cited journal (p < 0.001). These data may assist in designating core knowledge competency in pediatric craniofacial surgery for plastic surgery residents. A further understanding of PSITE utility for core knowledge competency in pediatric craniofacial surgery would be the focus of future work. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Correlations of frontal lip-line canting with craniofacial morphology and muscular activity.

PubMed

Cho, Jin-Hyoung; Kim, Eun-Jung; Kim, Byeong-Chae; Cho, Ki-Hyun; Lee, Ki-Heon; Hwang, Hyeon-Shik

2007-09-01

The purpose of this study was to investigate factors affecting lip-line canting by using musculoskeletal analyses. Fifty-six adults with lip-line canting were selected as subjects. They were divided into 3 groups according to the changes of lip line during smiling: increasing (group I), decreasing (group D), and minimal (group M). Lip-line canting at rest was correlated to craniofacial morphology and muscular activity: Regarding craniofacial morphology, various craniofacial measurements in lateral and frontal cephalograms were used, including inclination of the tongue blade placed across both first molars. The zygomaticus major was the focus of the measurement of muscular activity affecting lip-line canting, and its activity during smiling was evaluated by using a needle electrode. In group I, lip-line canting at rest showed a significant correlation with the right-left (R/L) difference of muscular activity, but no significant correlation with the measurements of craniofacial morphology. In group D, lip-line canting showed a positive correlation with the measurements of craniofacial morphology, such as the inclination of the tongue blade, and a negative correlation with the R/L difference of muscular activity. In group M, lip-line canting showed no significant correlation with the R/L difference of muscular activity, but a significant correlation with inclination of the tongue blade. The results indicate that lip-line canting is caused by craniofacial morphology when the change of lip-line canting during smiling is minimal, whereas lip-line canting is affected by the R/L difference of muscular activity in addition to craniofacial morphology when the cant of lip line markedly changes during smiling. The findings suggest that the cause of lip-line canting can be identified easily by the change of canting during smiling, without complicated musculoskeletal analyses.

Cleft Palate-Craniofacial Journal 50th anniversary editorial board commentary: anatomy, basic sciences, and genetics--then and now.

PubMed

Mooney, Mark P; Cooper, Gregory M; Marazita, Mary L

2014-05-01

To celebrate the 50th year of the Cleft Palate-Craniofacial Journal we look back to where we started in 1964 and where we are now, and we speculate about directions for the future in a "Then and Now" editorial series. This editorial examines changing trends and perspectives in anatomical, basic science, and genetic studies published in this 50-year interval. In volume 1 there were 45 total papers, seven (16%) of which were peer-reviewed basic science and genetic articles published: four in anatomy, three in craniofacial biology, and none in genetics. In contrast, in volume 50, of 113 articles there were 47 (42%) peer-reviewed basic science and genetic articles published: 30 in anatomy, five in craniofacial biology, and 12 in genetics. Topical analysis of published manuscripts then and now reveal that similar topics in anatomy and craniofacial biology are still being researched today (e.g., phenotypic variability, optimal timing of surgery, presurgical orthopedics, bone grafting); whereas, most of the more recent papers use advanced technology to address old questions. In contrast, genetic publications have clearly increased in frequency during the last 50 years, which parallels advances in the field during this time. However, all of us have noticed that the more "cutting-edge" papers in these areas are not being submitted for publication to the journal, but instead to discipline-specific journals. Concerted efforts are therefore indicated to attract and publish these cutting-edge papers in order to keep the Cleft Palate-Craniofacial Journal in the forefront of orofacial cleft and craniofacial anomaly research and to provide a valuable service to American Cleft Palate-Craniofacial Association members.

Assessing Species-specific Contributions To Craniofacial Development Using Quail-duck Chimeras

PubMed Central

Fish, Jennifer L.; Schneider, Richard A.

2014-01-01

The generation of chimeric embryos is a widespread and powerful approach to study cell fates, tissue interactions, and species-specific contributions to the histological and morphological development of vertebrate embryos. In particular, the use of chimeric embryos has established the importance of neural crest in directing the species-specific morphology of the craniofacial complex. The method described herein utilizes two avian species, duck and quail, with remarkably different craniofacial morphology. This method greatly facilitates the investigation of molecular and cellular regulation of species-specific pattern in the craniofacial complex. Experiments in quail and duck chimeric embryos have already revealed neural crest-mediated tissue interactions and cell-autonomous behaviors that regulate species-specific pattern in the craniofacial skeleton, musculature, and integument. The great diversity of neural crest derivatives suggests significant potential for future applications of the quail-duck chimeric system to understanding vertebrate development, disease, and evolution. PMID:24962088

Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects.

PubMed

De Mori, Roberta; Romani, Marta; D'Arrigo, Stefano; Zaki, Maha S; Lorefice, Elisa; Tardivo, Silvia; Biagini, Tommaso; Stanley, Valentina; Musaev, Damir; Fluss, Joel; Micalizzi, Alessia; Nuovo, Sara; Illi, Barbara; Chiapparini, Luisa; Di Marcotullio, Lucia; Issa, Mahmoud Y; Anello, Danila; Casella, Antonella; Ginevrino, Monia; Leggins, Autumn Sa'na; Roosing, Susanne; Alfonsi, Romina; Rosati, Jessica; Schot, Rachel; Mancini, Grazia Maria Simonetta; Bertini, Enrico; Dobyns, William B; Mazza, Tommaso; Gleeson, Joseph G; Valente, Enza Maria

2017-10-05

The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans. Through whole-exome sequencing in subjects with Joubert syndrome, we identified four children from two unrelated families carrying homozygous missense variants in SUFU. The children presented congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and postaxial polydactyly. Two siblings also showed polymicrogyria. Molecular dynamics simulation predicted random movements of the mutated residues, with loss of the native enveloping movement of the binding site around its ligand GLI3. Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. In turn, this impaired SUFU-mediated repression of the SHH pathway, as shown by altered expression levels of several target genes. We demonstrate that germline hypomorphic variants of SUFU cause deregulation of SHH signaling, resulting in recessive developmental defects of the CNS and limbs which share features with both SHH-related disorders and ciliopathies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Preliminary development of a workstation for craniomaxillofacial surgical procedures: introducing a computer-assisted planning and execution system.

PubMed

Gordon, Chad R; Murphy, Ryan J; Coon, Devin; Basafa, Ehsan; Otake, Yoshito; Al Rakan, Mohammed; Rada, Erin; Susarla, Srinivas; Susarla, Sriniras; Swanson, Edward; Fishman, Elliot; Santiago, Gabriel; Brandacher, Gerald; Liacouras, Peter; Grant, Gerald; Armand, Mehran

2014-01-01

Facial transplantation represents one of the most complicated scenarios in craniofacial surgery because of skeletal, aesthetic, and dental discrepancies between donor and recipient. However, standard off-the-shelf vendor computer-assisted surgery systems may not provide custom features to mitigate the increased complexity of this particular procedure. We propose to develop a computer-assisted surgery solution customized for preoperative planning, intraoperative navigation including cutting guides, and dynamic, instantaneous feedback of cephalometric measurements/angles as needed for facial transplantation and other related craniomaxillofacial procedures. We developed the Computer-Assisted Planning and Execution (CAPE) workstation to assist with planning and execution of facial transplantation. Preoperative maxillofacial computed tomography (CT) scans were obtained on 4 size-mismatched miniature swine encompassing 2 live face-jaw-teeth transplants. The system was tested in a laboratory setting using plastic models of mismatched swine, after which the system was used in 2 live swine transplants. Postoperative CT imaging was obtained and compared with the preoperative plan and intraoperative measures from the CAPE workstation for both transplants. Plastic model tests familiarized the team with the CAPE workstation and identified several defects in the workflow. Live swine surgeries demonstrated utility of the CAPE system in the operating room, showing submillimeter registration error of 0.6 ± 0.24 mm and promising qualitative comparisons between intraoperative data and postoperative CT imaging. The initial development of the CAPE workstation demonstrated that integration of computer planning and intraoperative navigation for facial transplantation are possible with submillimeter accuracy. This approach can potentially improve preoperative planning, allowing ideal donor-recipient matching despite significant size mismatch, and accurate surgical execution for numerous types of craniofacial and orthognathic surgical procedures.

Free anterolateral thigh flap for reconstruction of major craniofacial defects.

PubMed

Amin, Ayman; Rifaat, Mohammed; Civantos, Francisco; Weed, Donald; Abu-Sedira, Mohammed; Bassiouny, Mahmoud

2006-02-01

Free-tissue transfer has revolutionized skull-base surgery by expanding the ability to perform cranial base resection and by improving the quality of reconstruction. The anterolateral thigh flap has come recently into use in the field of head and neck reconstruction. Its role in craniofacial and midface reconstruction has not been specifically defined. This study involved a total of 18 patients who were treated over a 5-year period from 1998 to 2003. Seventeen patients had locally advanced head and neck cancer, requiring craniofacial resection, and one patient had a complicated gun shot wound of the forehead. Thirteen patients were treated at the National Cancer Institute, Cairo University, Egypt, and five patients at the University of Miami, Florida. The patients presented with defects of the anterior skull base (5), lateral skull base (3), scalp and calvarium (3), and the midface (7). The anterolateral thigh flap was used as a myocutaneous flap in 11 cases and as a perforator fasciocutaneous flap in seven cases. Musculocutaneous perforators supplied the majority of flaps (17/18). Total flap survival occurred in 17 cases; one patient developed complete flap necrosis. The most commonly used recipient vessels were the facial vessels and the external jugular vein. Major complications included one case with meningitis; the patient died after failure of treatment. Another patient died 6 weeks postoperatively from pulmonary embolism. One patient developed CSF leak that stopped spontaneously. In addition, two patients developed minor wound dehiscence that healed spontaneously. The donor-site wound healed without problems except in two cases. One patient had an incomplete take of the skin graft; the other developed wound infection and superficial sloughing. Both wounds healed spontaneously. In addition to the feasibility of simultaneous flap harvesting with tumor resection, the flap's advantage in skull base reconstruction is its reliable blood supply, which can provide adequate dural cover and protection of the brain. Its size and moderate thickness are suitable for reconstruction of scalp and calvarial defects. The abundance of reliably vascularized fat in the flap may be an advantage in long-term maintenance of the volume of the flap in midface reconstruction. Similar to other soft tissue flaps, additional skeletal reconstruction may still be required to achieve an optimal functional and aesthetic result.

75 FR 13561 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... & Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as... Craniofacial Research Council. The meeting will be open to the public as indicated below, with attendance... set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications...

78 FR 50066 - National Institute of Dental and Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... and Craniofacial Research; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... National Advisory Dental and Craniofacial Research Council. The meeting will be open to the public as... accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended...

Msx homeobox gene family and craniofacial development.

PubMed

Alappat, Sylvia; Zhang, Zun Yi; Chen, Yi Ping

2003-12-01

Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the phenotypic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice. Key words: Msx genes, craniofacial, tooth, cleft palate, suture, development, transcription factor, signaling molecule.

Concurrent cervical and craniofacial pain. A review of empiric and basic science evidence.

PubMed

Browne, P A; Clark, G T; Kuboki, T; Adachi, N Y

1998-12-01

Because many patients present themselves for treatment with both craniofacial and craniocervical pain, 2 questions arise: (1) What are the sensory and motor consequences of dysfunction in either of these areas on the other? (2) Do craniofacial and craniocervical pain have a similar cause? These questions formed the impetus for this review article. The phenomenon of concurrent pain in craniofacial and cervical structures is considered, and clinical reports and opinions are presented regarding theories of cervical-to-craniofacial and craniofacial-to-cervical pain referral. Because pain referral between these 2 areas requires anatomic and functional connectivity between trigeminally and cervically innervated structures, basic neurophysiologic and neuroanatomic literature is reviewed. The published data clearly demonstrate neurophysiologic and structural convergence of cervical sensory and muscle afferent inputs onto trigeminal subnucleus caudalis nociceptive and non-nociceptive neurons. Moreover, changes in metabolic activity and blood flow in the brainstem and cervical dorsal horn of the spinal cord in both monkeys and cats have been demonstrated after electric stimulation of the V1-innervated superior sagittal sinus. In conclusion, the animal experimental data support the findings of human empiric and experimental studies, which suggest that strong connectivity exists between trigeminal and cervical motor and sensory responses.

Craniofacial reconstruction evaluation by geodesic network.

PubMed

Zhao, Junli; Liu, Cuiting; Wu, Zhongke; Duan, Fuqing; Wang, Kang; Jia, Taorui; Liu, Quansheng

2014-01-01

Craniofacial reconstruction is to estimate an individual's face model from its skull. It has a widespread application in forensic medicine, archeology, medical cosmetic surgery, and so forth. However, little attention is paid to the evaluation of craniofacial reconstruction. This paper proposes an objective method to evaluate globally and locally the reconstructed craniofacial faces based on the geodesic network. Firstly, the geodesic networks of the reconstructed craniofacial face and the original face are built, respectively, by geodesics and isogeodesics, whose intersections are network vertices. Then, the absolute value of the correlation coefficient of the features of all corresponding geodesic network vertices between two models is taken as the holistic similarity, where the weighted average of the shape index values in a neighborhood is defined as the feature of each network vertex. Moreover, the geodesic network vertices of each model are divided into six subareas, that is, forehead, eyes, nose, mouth, cheeks, and chin, and the local similarity is measured for each subarea. Experiments using 100 pairs of reconstructed craniofacial faces and their corresponding original faces show that the evaluation by our method is roughly consistent with the subjective evaluation derived from thirty-five persons in five groups.

Facial clefts and facial dysplasia: revisiting the classification.

PubMed

Mazzola, Riccardo F; Mazzola, Isabella C

2014-01-01

Most craniofacial malformations are identified by their appearance. The majority of the classification systems are mainly clinical or anatomical, not related to the different levels of development of the malformation, and underlying pathology is usually not taken into consideration. In 1976, Tessier first emphasized the relationship between soft tissues and the underlying bone stating that "a fissure of the soft tissue corresponds, as a general rule, with a cleft of the bony structure". He introduced a cleft numbering system around the orbit from 0 to 14 depending on its relationship to the zero line (ie, the vertical midline cleft of the face). The classification, easy to understand, became widely accepted because the recording of the malformations was simple and communication between observers facilitated. It represented a great breakthrough in identifying craniofacial malformations, named clefts by him. In the present paper, the embryological-based classification of craniofacial malformations, proposed in 1983 and in 1990 by us, has been revisited. Its aim was to clarify some unanswered questions regarding apparently atypical or bizarre anomalies and to establish as much as possible the moment when this event occurred. In our opinion, this classification system may well integrate the one proposed by Tessier and tries at the same time to find a correlation between clinical observation and morphogenesis.Terminology is important. The overused term cleft should be reserved to true clefts only, developed from disturbances in the union of the embryonic facial processes, between the lateronasal and maxillary process (or oro-naso-ocular cleft); between the medionasal and maxillary process (or cleft of the lip); between the maxillary processes (or cleft of the palate); and between the maxillary and mandibular process (or macrostomia).For the other types of defects, derived from alteration of bone production centers, the word dysplasia should be used instead. Facial dysplasias have been ranged in a helix form and named after the site of the developmental arrest. Thus, an internasal, nasal, nasomaxillary, maxillary and malar dysplasia, depending on the involved area, have been identified.The classification may provide a useful guide in better understanding the morphogenesis of rare craniofacial malformations.

Craniofacial morphology and dental maturity in children with reduced somatic growth of different aetiology and the effect of growth hormone treatment.

PubMed

Davidopoulou, Sotiria; Chatzigianni, Athina

2017-12-01

Children with reduced somatic growth may present various endocrinal diseases, especially growth hormone deficiency (GHD), idiopathic short stature (ISS), chromosomal aberrations, or genetic disorders. In an attempt to normalize the short stature, growth hormone (GH) is administered to these children. The aim of this literature review was to collect information about the craniofacial morphology and dental maturity in these children and to present the existing knowledge on the effect of GH treatment on the above structures.This review demonstrated that regardless of the origin of the somatic growth retardation, these children show similar craniofacial features, such as short length of the cranial base and the mandible, increased lower facial height, retropositioned mandible, and obtuse gonion angle. On the other hand, dental maturation does not demonstrate a specific pattern. Except for the above findings, muscle alterations seem to be present in individuals with short stature, who present low body muscle mass and strength, while studies on their craniofacial muscles seem to be lacking. After GH administration, the exact amount and pattern of craniofacial growth is unpredictable; however, the facial convexity decreases, mandibular length increases, and posterior facial height increases, while tooth eruption remains unaffected. Thus, it is of great importance to gain more insight into the craniofacial growth of treated and untreated children with reduced somatic growth so that the influence of GH therapy on the various craniofacial structures could be ascertained and proper orthodontic treatment could be selected.

Efficient free-form surface representation with application in orthodontics

NASA Astrophysics Data System (ADS)

Yamany, Sameh M.; El-Bialy, Ahmed M.

1999-03-01

Orthodontics is the branch of dentistry concerned with the study of growth of the craniofacial complex. The detection and correction of malocclusion and other dental abnormalities is one of the most important and critical phases of orthodontic diagnosis. This paper introduces a system that can assist in automatic orthodontics diagnosis. The system can be used to classify skeletal and dental malocclusion from a limited number of measurements. This system is not intended to deal with several cases but is aimed at cases more likely to be encountered in epidemiological studies. Prior to the measurement of the orthodontics parameters, the position of the teeth in the jaw model must be detected. A new free-form surface representation is adopted for the efficient and accurate segmentation and separation of teeth from a scanned jaw model. THe new representation encodes the curvature and surface normal information into a 2D image. Image segmentation tools are then sued to extract structures of high/low curvature. By iteratively removing these structures, individual teeth surfaces are obtained.

Craniofacial skeletal defects of adult zebrafish glypican 4 (knypek) mutants

PubMed Central

LeClair, Elizabeth E.; Mui, Stephanie R.; Huang, Angela; Topczewska, Jolanta M.; Topczewski, Jacek

2010-01-01

The heparan sulfate proteoglycan Glypican 4 (Gpc4) is part of the Wnt/planar cell polarity pathway, which is required for convergence and extension during zebrafish gastrulation. To observe Glypican 4-deficient phenotypes at later stages, we rescued gpc4−/− (knypek) homozygotes and raised them for more than one year. Adult mutants showed diverse cranial malformations of both dermal and endochondral bones, ranging from shortening of the rostral-most skull to loss of the symplectic. Additionally, the adult palatoquadrate cartilage was disorganized, with abnormal chondrocyte orientation. To understand how the palatoquadrate cartilage normally develops, we examined a juvenile series of wild type and mutant specimens. This identified two novel domains of elongated chondrocytes in the larval palatoquadrate, which normally form prior to endochondral ossification. In contrast, gpc4−/− larvae never form these domains, suggesting a failure of chondrocyte orientation, though not differentiation. Our findings implicate Gpc4 in the regulation of zebrafish cartilage and bone morphogenesis. PMID:19777561

Morphometric analysis of treatment effects of bone-anchored maxillary protraction in growing Class III patients

PubMed Central

De Clerck, H. J.; Cevidanes, L. H.; Franchi, L.

2011-01-01

The aim of the present morphometric investigation was to evaluate the effects of bone-anchored maxillary protraction (BAMP) in the treatment of growing patients with Class III malocclusion. The shape and size changes in the craniofacial configuration of a sample of 26 children with Class III malocclusions consecutively treated with the BAMP protocol were compared with a matched sample of 15 children with untreated Class III malocclusions. All subjects in the two groups were at a prepubertal stage of skeletal development at time of first observation. Average duration of treatment was 14 months. Significant treatment-induced modifications involved both the maxilla and the mandible. The most evident deformation consisted of marked forward displacement of the maxillary complex with more moderate favourable effects in the mandible. Deformations in the vertical dimension were not detected. The significant deformations were associated with significant differences in size in the group treated with the BAMP protocol. PMID:21187527

A gene for cleidocranial dysplasia to the short arm of chromosome 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feldman, G.F.; Muenke, M.; Robin, N.H.

1995-04-01

Cleidocranial dysplasia (CCD) is an autosomal dominant generalized bone dysplasia characterized by mild-to-moderate short stature, clavicular aplasia or hypoplasia, supernumerary and ectopic teeth, delayed eruption of secondary teeth, a characteristic craniofacial appearance, and a variety of other skeletal anomalies. We have performed linkage studies in five families with CCD, with 24 affected and 20 unaffected individuals, using microsatellite markers spanning two candidate regions on chromosomes 8q and 6. The strongest support for linkage was with chromosome 6p microsatellite marker D6S282 with a two-point lod score of 4.84 ({theta} = .03). Furthermore, the multipoint lod score was 5.70 in the intervalmore » between D6S282 and D6S291. These data show that the gene for autosomal dominant CCD is located within a 19-cM interval on the short arm of chromosome 6, between D6S282 and D6S291. 25 refs., 3 figs., 1 tab.« less

Cephalometric norms for the Chinese: a compilation of existing data.

PubMed

Moate, S J; Darendeliler, M A

2002-03-01

The intention of this paper is to compile Chinese cephalometric norms for a more objective orthodontic diagnosis of Chinese patients so that their orthodontic treatment may be better planned. Studies on cephalometric norms of Chinese and subjects of Chinese descent were reviewed. Some important studies were available only in the Chinese journals and they were especially procured and translated for this purpose. A normal range of anteroposterior apical base differences, concomitant nterincisal inclinations and locations, were derived from different Chinese groups and were tabulated. The differences between Chinese and Caucasian norms are discussed. A distinctive craniofacial and dental pattern of the people of Chinese origin was found and is reflected in the cephalometric measurements. Compared with Caucasian norms, Chinese norms have skeletal, dental and soft-tissue variations. The Chinese have a shorter cranial base and a larger ANB. The Chinese dentition demonstrates greater bimaxillary-alveolar protrusion, with a decreased interincisal angle. The Chinese soft-tissue profile shows a less prominent nose, with a less obtuse nasolabial angle, and more protrusive lips.

Effects of posttreatment skeletal maturity measured with the cervical vertebral maturation method on incisor alignment relapse.

PubMed

Fudalej, Piotr; Rothe, Laura E; Bollen, Anne-Marie

2008-08-01

Our aim was to test the hypothesis that relapse of incisor alignment is associated with skeletal maturity at the end of treatment, as assessed with the cervical vertebral maturation (CVM) method. This was a case-control study with information from the postretention database at the University of Washington. Mandibular incisor irregularity (II) at least 10 years out of retention (T3) was used to define the subjects (II >6 mm, relapse group) and the controls (II <3.5 mm, stable group). The following model measurements were made: II at pretreatment (T1), II at posttreatment (T2), and intercanine width at T1 and T2. On cephalograms taken T2, the CVM status was determined. Logistic regression analyses were used to determine the association between relapse and CVM status after treatment. The models were adjusted for potentially confounding variables (II at pretreatment and posttreatment, intercanine width change during treatment, sex, age at T2, and treatment alternatives). No association between CVM stage at T2 and relapse was found (P = 0.89). Both groups had similar distributions of the CVM stages (P >0.05). Pretreatment II and postretention time were found to be correlated with long-term incisor stability (P = 0.007 and 0.034, respectively). Sex was not related to relapse (P = 0.33). Maturity of craniofacial structures at the end of treatment evaluated with the CVM method is not associated with long-term stability of incisor alignment.

Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant: A Reconstructive Solution for the Full Face and Total Scalp Burn.

PubMed

Sosin, Michael; Ceradini, Daniel J; Levine, Jamie P; Hazen, Alexes; Staffenberg, David A; Saadeh, Pierre B; Flores, Roberto L; Sweeney, Nicole G; Bernstein, G Leslie; Rodriguez, Eduardo D

2016-07-01

Reconstruction of extensive facial and scalp burns can be increasingly challenging, especially in patients that have undergone multiple procedures with less than ideal outcomes resulting in restricting neck and oral contractures, eyelid dysfunction, and suboptimal aesthetic appearance. To establish a reconstructive solution for this challenging deformity, a multidisciplinary team was assembled to develop the foundation to a facial vascularized composite allotransplantation program. The strategy of developing and executing a clinical transplant was derived on the basis of fostering a cohesive and supportive institutional clinical environment, implementing computer software and advanced technology, establishing a cadaveric transplant model, performing a research facial procurement, and selecting an optimal candidate with the aforementioned burn defect who was well informed and had the desire to undergo face transplantation. Approval from the institutional review board and organ procurement organization enabled our face transplant team to successfully perform a total face, eyelids, ears, scalp, and skeletal subunit transplant in a 41-year-old man with a full face and total scalp burn. The culmination of knowledge attained from previous experiences continues to influence the progression of facial vascularized composite allotransplantation. This surgical endeavor methodically and effectively synchronized the fundamental principles of aesthetic, craniofacial, and microvascular surgery to restore appearance and function to a patient suffering from failed conventional surgery for full face and total scalp burns. This procedure represents the most extensive soft-tissue clinical face transplant performed to date. Therapeutic, V.

Heritability of Craniofacial Structures in Normal Subjects and Patients with Sleep Apnea

PubMed Central

Chi, Luqi; Comyn, Francois-Louis; Keenan, Brendan T.; Cater, Jacqueline; Maislin, Greg; Pack, Allan I.; Schwab, Richard J.

2014-01-01

Objectives: Accumulating evidence has shown that there is a genetic contribution to obstructive sleep apnea (OSA).The objectives were to use magnetic resonance imaging (MRI) cephalometry to (1) confirm heritability of craniofacial risk factors for OSA previously shown by cephalometrics; and (2) examine the heritability of new craniofacial structures that are measurable with MRI. Design: A sib pair “quad” design examining apneics, apneic siblings, controls, and control siblings. The study design used exact matching on ethnicity and sex, frequency matching on age, and statistical control for differences in age, sex, ethnicity, height, and weight. Setting: Academic medical center. Patients: We examined 55 apneic probands (apnea-hypopnea index [AHI]: 46.8 ± 33.5 events/h), 55 proband siblings (AHI: 11.1 ± 15.9 events/h), 55 controls (AHI: 2.2 ± 1.7 events/h), and 55 control siblings (AHI: 4.1 ± 4.0 events/h). Interventions: N/A. Measurements and Results: Five independent domains reflecting different aspects of the craniofacial structure were examined. We confirmed heritability of sella–nasion–subspinale (38%, P = 0.002), saddle angle (55%, P < 0.0001), mandibular length (24%, P = 0.02) and lower facial height (33%, P = 0.006) previously measured by cephalometry. In addition, the current study added new insights by demonstrating significant heritability of mandibular width (30%, P = 0.005), maxillary width (47%, P < 0.0001), distance from the hyoid bone to the retropogonion (36%, P = 0.0018) and size of the oropharyngeal space (31%, P = 0.004). Finally, our data indicate that heritability of the craniofacial structures is similar in normal patients and those with apnea. Conclusions: The data support our a priori hypothesis that the craniofacial structures that have been associated with obstructive sleep apnea (OSA) are heritable. We have demonstrated heritability for several intermediate craniofacial phenotypes for OSA. Thus, we believe that future studies should be able to identify genes associated with these intermediate craniofacial phenotypes. Citation: Chi L, Comyn FL, Keenan BT, Cater J, Maislin G, Pack AI, Schwab RJ. Heritability of craniofacial structures in normal subjects and patients with sleep apnea. SLEEP 2014;37(10):1689-1698. PMID:25197806

Contrasting patterns of RUNX2 repeat variations are associated with palate shape in phyllostomid bats and New World primates.

PubMed

Ferraz, Tiago; Rossoni, Daniela M; Althoff, Sérgio L; Pissinatti, Alcides; Paixão-Cortês, Vanessa R; Bortolini, Maria Cátira; González-José, Rolando; Marroig, Gabriel; Salzano, Francisco M; Gonçalves, Gislene L; Hünemeier, Tábita

2018-05-18

Establishing the genetic basis that underlies craniofacial variability in natural populations is one of the main topics of evolutionary and developmental studies. One of the genes associated with mammal craniofacial variability is RUNX2, and in the present study we investigated the association between craniofacial length and width and RUNX2 across New World bats (Phyllostomidae) and primates (Catarrhini and Platyrrhini). Our results showed contrasting patterns of association between the glutamate/alanine ratios (Q/A ratio) and palate shape in these highly diverse groups. In phyllostomid bats, we found an association between shorter/broader faces and increase of the Q/A ratio. In New World monkeys (NWM) there was a positive correlation of increasing Q/A ratios to more elongated faces. Our findings reinforced the role of the Q/A ratio as a flexible genetic mechanism that would rapidly change the time of skull ossification throughout development. However, we propose a scenario in which the influence of this genetic adjustment system is indirect. The Q/A ratio would not lead to a specific phenotype, but throughout the history of a lineage, would act along with evolutionary constraints, as well as other genes, as a facilitator for adaptive morphological changes.

Pediatric considerations in craniofacial trauma.

PubMed

Koch, Bernadette L

2014-08-01

In many respects, craniofacial trauma in children is akin to that in adults. The appearance of fractures and associated injuries is frequently similar. However, the frequencies of different types of fractures and patterns of injury in younger children vary depending on the age of the child. In addition, there are unique aspects that must be considered when imaging the posttraumatic pediatric face. Some of these are based on normal growth and development of the skull base and craniofacial structures, and others on the varying etiologies and mechanisms of craniofacial injury in children, such as injuries related to toppled furniture, nonaccidental trauma, all-terrain vehicle accidents, and impalement injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

[Observational study of craniofacial growth and development in Mexican children].

PubMed

Fijikami, T K; Cedeño Pacheco, E

1991-01-01

The election of a investigation about craniofacial growing and development in Mexican children, was done due to a lack of national information in this rubric and as a fundamental part of the "growing and development in the scholastic" module of the Universidad Autónoma Metropolitana-Xochimilco, which work hypothesis was that "craniofacial growing and development in Mexican, 6 to 12 children in Xochimilco area are due to nutritional deficiency, second dentition eruption delay and dental maloclution "which was totality confirmed in a 100 Mexican facial characteristic children field work study, with cephalometric studies which permit to determine the craniofacial growing standard. This study was corroborated with a 40 children, 4 years later follow up.

Advances in Bioprinting Technologies for Craniofacial Reconstruction.

PubMed

Visscher, Dafydd O; Farré-Guasch, Elisabet; Helder, Marco N; Gibbs, Susan; Forouzanfar, Tymour; van Zuijlen, Paul P; Wolff, Jan

2016-09-01

Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years. Copyright © 2016 Elsevier Ltd. All rights reserved.

Normal/Modern: Reconstructive Surgery in a Mexican Public Hospital.

PubMed

Taylor-Alexander, Samuel

2017-10-01

A growing corpus of anthropological scholarship demonstrates how science and medicine in Mexico are imbued by national concerns with modernization. Drawing on ethnographic research in a public hospital located in the south of Mexico City, I unpack one manifestation of this dynamic, which is the conjugation of the normal and the modern in Mexican reconstructive surgery. The aspiration toward normality underlies everyday clinic practices and relationships in this field, including why parents want surgery for their children and how doctors see their patients and their responsibilities toward them. It is also central to the professional ethic of reconstructive surgeons. I argue that the realities of health care provision in Mexico coalesced with this ethic to produce reconstructive surgeons as political subjects. They aimed to modernize craniofacial surgery in Mexico and so make the bodies of craniofacial patients normal.

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation.

PubMed

Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A

2016-01-21

Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype-phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1(+/-) mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies.

Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation

PubMed Central

Sakai, Daisuke; Dixon, Jill; Achilleos, Annita; Dixon, Michael; Trainor, Paul A.

2016-01-01

Craniofacial anomalies account for approximately one-third of all birth defects and are a significant cause of infant mortality. Since the majority of the bones, cartilage and connective tissues that comprise the head and face are derived from a multipotent migratory progenitor cell population called the neural crest, craniofacial disorders are typically attributed to defects in neural crest cell development. Treacher Collins syndrome (TCS) is a disorder of craniofacial development and although TCS arises primarily through autosomal dominant mutations in TCOF1, no clear genotype–phenotype correlation has been documented. Here we show that Tcof1 haploinsufficiency results in oxidative stress-induced DNA damage and neuroepithelial cell death. Consistent with this discovery, maternal treatment with antioxidants minimizes cell death in the neuroepithelium and substantially ameliorates or prevents the pathogenesis of craniofacial anomalies in Tcof1+/− mice. Thus maternal antioxidant dietary supplementation may provide an avenue for protection against the pathogenesis of TCS and similar neurocristopathies. PMID:26792133

Sleep disorders and chronic craniofacial pain: Characteristics and management possibilities.

PubMed

Almoznino, Galit; Benoliel, Rafael; Sharav, Yair; Haviv, Yaron

2017-06-01

Chronic craniofacial pain involves the head, face and oral cavity and is associated with significant morbidity and high levels of health care utilization. A bidirectional relationship is suggested in the literature for poor sleep and pain, and craniofacial pain and sleep are reciprocally related. We review this relationship and discuss management options. Part I reviews the relationship between pain and sleep disorders in the context of four diagnostic categories of chronic craniofacial pain: 1) primary headaches: migraines, tension-type headache (TTH), trigeminal autonomic cephalalgias (TACs) and hypnic headache, 2) secondary headaches: sleep apnea headache, 3) temporomandibular joint disorders (TMD) and 4) painful cranial neuropathies: trigeminal neuralgia, post-herpetic trigeminal neuropathy, painful post-traumatic trigeminal neuropathy (PTTN) and burning mouth syndrome (BMS). Part II discusses the management of patients with chronic craniofacial pain and sleep disorders addressing the factors that modulate the pain experience as well as sleep disorders and including both non-pharmacological and pharmacological modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomaterials for Craniofacial Bone Engineering

PubMed Central

Tevlin, R.; McArdle, A.; Atashroo, D.; Walmsley, G.G.; Senarath-Yapa, K.; Zielins, E.R.; Paik, K.J.; Longaker, M.T.; Wan, D.C.

2014-01-01

Conditions such as congenital anomalies, cancers, and trauma can all result in devastating deficits of bone in the craniofacial skeleton. This can lead to significant alteration in function and appearance that may have significant implications for patients. In addition, large bone defects in this area can pose serious clinical dilemmas, which prove difficult to remedy, even with current gold standard surgical treatments. The craniofacial skeleton is complex and serves important functional demands. The necessity to develop new approaches for craniofacial reconstruction arises from the fact that traditional therapeutic modalities, such as autologous bone grafting, present myriad limitations and carry with them the potential for significant complications. While the optimal bone construct for tissue regeneration remains to be elucidated, much progress has been made in the past decade. Advances in tissue engineering have led to innovative scaffold design, complemented by progress in the understanding of stem cell–based therapy and growth factor enhancement of the healing cascade. This review focuses on the role of biomaterials for craniofacial bone engineering, highlighting key advances in scaffold design and development. PMID:25139365

Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

PubMed Central

Gaihre, Bipin; Uswatta, Suren; Jayasuriya, Ambalangodage C.

2017-01-01

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies. PMID:29156629

PDGFRβ regulates craniofacial development through homodimers and functional heterodimers with PDGFRα.

PubMed

Fantauzzo, Katherine A; Soriano, Philippe

2016-11-01

Craniofacial development is a complex morphogenetic process, disruptions in which result in highly prevalent human birth defects. While platelet-derived growth factor (PDGF) receptor α (PDGFRα) has well-documented functions in this process, the role of PDGFRβ in murine craniofacial development is not well established. We demonstrate that PDGFRα and PDGFRβ are coexpressed in the craniofacial mesenchyme of mid-gestation mouse embryos and that ablation of Pdgfrb in the neural crest lineage results in increased nasal septum width, delayed palatal shelf development, and subepidermal blebbing. Furthermore, we show that the two receptors genetically interact in this lineage, as double-homozygous mutant embryos exhibit an overt facial clefting phenotype more severe than that observed in either single-mutant embryo. We reveal a physical interaction between PDGFRα and PDGFRβ in the craniofacial mesenchyme and demonstrate that the receptors form functional heterodimers with distinct signaling properties. Our studies thus uncover a novel mode of signaling for the PDGF family during vertebrate development. © 2016 Fantauzzo and Soriano; Published by Cold Spring Harbor Laboratory Press.

Oral appliances and functional orthopaedic appliances for obstructive sleep apnoea in children.

PubMed

Carvalho, Fernando R; Lentini-Oliveira, Débora A; Prado, Lucila Bf; Prado, Gilmar F; Carvalho, Luciane Bc

2016-10-05

Apnoea is a breathing disorder marked by the absence of airflow at the nose or mouth. In children, risk factors include adenotonsillar hypertrophy, obesity, neuromuscular disorders and craniofacial anomalies. The most common treatment for obstructive sleep apnoea syndrome (OSAS) in childhood is adeno-tonsillectomy. This approach is limited by its surgical risks, mostly in children with comorbidities and, in some patients, by recurrence that can be associated with craniofacial problems. Oral appliances and functional orthopaedic appliances have been used for patients who have OSAS and craniofacial anomalies because they hold the lower jaw (mandible) forwards which potentially enlarges the upper airway and increases the upper airspace, improving the respiratory function. To assess the effects of oral appliances or functional orthopaedic appliances for obstructive sleep apnoea in children. We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 7 April 2016); Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 7 April 2016); MEDLINE Ovid (1946 to 7 April 2016); Embase Ovid (1980 to 7 April 2016); LILACS BIREME (from 1982 to 7 April 2016); BBO BIREME (from 1986 to 7 April 2016) and SciELO Web of Science (from 1997 to 7 April 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials on 7 April 2016. We placed no restrictions on the language or date of publication when searching the electronic databases. All randomised or quasi-randomised controlled trials comparing all types of oral and functional orthopaedic appliances with placebo or no treatment, in children 15 years old or younger. reduction of apnoea to less than one episode per hour. dental and skeletal relationship, sleep parameters improvement, cognitive and phonoaudiological function, behavioural problems, quality of life, side effects (tolerability) and economic evaluation. Two review authors screened studies and extracted data independently. Authors were contacted for additional information. We calculated risk ratios with 95% confidence intervals for all important dichotomous outcomes. We assessed the quality of the evidence of included studies using GRADEpro software. The initial search identified 686 trials. Only one trial, reporting the results from a total of 23 children and comparing an oral appliance to no treatment, was suitable for inclusion in the review. The trial assessed apnoea-hypopnoea, daytime symptoms (sleepiness, irritability, tiredness, school problems, morning headache, thirstiness in the morning, oral breathing and nasal stuffiness) and night-time symptoms (habitual snoring, restless sleep and nightmares measured by questionnaire). Results were inconsistent across outcomes measures and time points. The evidence was considered very low quality. There is insufficient evidence to support or refute the effectiveness of oral appliances and functional orthopaedic appliances for the treatment of obstructive sleep apnoea in children. Oral appliances or functional orthopaedic appliances may be considered in specified cases as an auxiliary in the treatment of children who have craniofacial anomalies which are risk factors for apnoea.

Craniofacial melorheostosis.

PubMed

McDermott, Meredith; Branstetter, Barton F; Seethala, Raja R

2008-01-01

Melorheostosis is a rare benign disease of cortical bone most frequently presenting as peripheral hyperostosis with a characteristic "melting wax" appearance on conventional radiographs. The disease most frequently affects the appendicular skeleton and is seen only rarely in the craniofacial bones. We discuss a case of melorheostosis in the nasal cavity and skull base with an atypical radiographic appearance and suggest findings that may differentiate craniofacial melorheostosis from more common entities in this region.

Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering.

PubMed

Obregon, F; Vaquette, C; Ivanovski, S; Hutmacher, D W; Bertassoni, L E

2015-09-01

Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side. © International & American Associations for Dental Research 2015.

Gap Junction Intercellular Communication: A Review of a Potential Platform to Modulate Craniofacial Tissue Engineering

PubMed Central

Rossello, Ricardo A.; Kohn, David H.

2009-01-01

Defects in craniofacial tissues, resulting from trauma, congenital abnormalities, oncologic resection or progressive deforming diseases, may result in aesthetic deformity, pain and reduced function. Restoring the structure, function and aesthetics of craniofacial tissues represents a substantial clinical problem in need of new solutions. More biologically-interactive biomaterials could potentially improve the treatment of craniofacial defects, and an understanding of developmental processes may help identify strategies and materials that can be used in tissue engineering. One such strategy that can potentially advance tissue engineering is cell–cell communication. Gap junction intercellular communication is the most direct way of achieving such signaling. Gap junction communication through connexin-mediated junctions, in particular connexin 43 (Cx43), plays a major role bone development. Given the important role of Cx43 in controlling development and differentiation, especially in bone cells, controlling the expression of Cx43 may provide control over cell-to-cell communication and may help overcome some of the challenges in craniofacial tissue engineering. Following a review of gap junctions in bone cells, the ability to enhance cell–cell communication and osteogenic differentiation via control of gap junctions is discussed, as is the potential utility of this approach in craniofacial tissue engineering. PMID:18481782

Craniofacial neurofibromatosis: treatment of the midface deformity.

PubMed

Singhal, Dhruv; Chen, Yi-Chieh; Tsai, Yueh-Ju; Yu, Chung-Chih; Chen, Hung Chang; Chen, Yu-Ray; Chen, Philip Kuo-Ting

2014-07-01

Craniofacial Neurofibromatosis is a benign but devastating disease. While the most common location of facial involvement is the orbito-temporal region, patients often present with significant mid-face deformities. We reviewed our experience with Craniofacial Neurofibromatosis from June 1981 to June 2011 and included patients with midface soft tissue deformities defined as gross alteration of nasal or upper lip symmetry. Data reviewed included the medical records and photobank. Over 30 years, 52 patients presented to and underwent surgical management for Craniofacial Neurofibromatosis at the Chang Gung Craniofacial Center. 23 patients (43%) demonstrated gross mid-facial deformities at initial evaluation. 55% of patients with lip deformities and 28% of patients with nasal deformities demonstrated no direct tumour involvement. The respective deformity was solely due to secondary gravitational effects from neurofibromas of the cheek subunit. Primary tumour infiltration of the nasal and/or labial subunits was treated with excision followed by various methods of reconstruction including lower lateral cartilage repositioning, forehead flaps, free flaps, and/or oral commissure suspension. Soft tissue deformities of the midface are very common in patients with Craniofacial Neurofibromatosis and profoundly affect overall aesthetic outcomes. Distinguishing primary from secondary involvement of the midface assists in surgical decision making. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Cranio-facial clefts in pre-hispanic America.

PubMed

Marius-Nunez, A L; Wasiak, D T

2015-10-01

Among the representations of congenital malformations in Moche ceramic art, cranio-facial clefts have been portrayed in pottery found in Moche burials. These pottery vessels were used as domestic items during lifetime and funerary offerings upon death. The aim of this study was to examine archeological evidence for representations of cranio-facial cleft malformations in Moche vessels. Pottery depicting malformations of the midface in Moche collections in Lima-Peru were studied. The malformations portrayed on pottery were analyzed using the Tessier classification. Photographs were authorized by the Larco Museo.Three vessels were observed to have median cranio-facial dysraphia in association with midline cleft of the lower lip with cleft of the mandible. ML001489 portrays a median cranio-facial dysraphia with an orbital cleft and a midline cleft of the lower lip extending to the mandible. ML001514 represents a median facial dysraphia in association with an orbital facial cleft and a vertical orbital dystopia. ML001491 illustrates a median facial cleft with a soft tissue cleft. Three cases of midline, orbital and lateral facial clefts have been portrayed in Moche full-figure portrait vessels. They represent the earliest registries of congenital cranio-facial malformations in ancient Peru. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The face, the future, and dental practice: how research in craniofacial biology will influence patient care.

PubMed

Townsend, G C; Brook, A H

2014-06-01

It has been a privilege to assemble a group of Australian and international researchers to produce a special issue of the Australian Dental Journal that reflects the cutting edge of research in different aspects of craniofacial biology, and also considers how these advances will influence future education and practice within dentistry. The aim of this special issue is to provide a collection of concept papers and critical reviews on key topics that cover both fundamental and applied research in craniofacial biology and to consider the clinical implications. To do this, four questions have been addressed that lead to the four sections of this issue. These are: How have we come to the present exciting position in craniofacial biology with breakthroughs over the past 50 years? What are current fundamental research topics that are helping us to understand more about craniofacial and general development, possibly leading to future clinical developments? What are the current applied research topics that will influence future clinical practice? Looking forward, what new developments in craniofacial biology may come about that will change the face of dental education and practice? The refereed papers in this special issue are grouped into the four sections that seek to respond to these demanding questions. © 2014 Australian Dental Association.

Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size.

PubMed

Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T; Weiss, Kenneth M; Mahaney, Michael C; Rogers, Jeffrey; Cheverud, James M

2018-02-01

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (V P ) and additive genetic (V A ) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution? We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the correlated response of a given EID due to selection on body mass alone. Covariates account for 1.2-91% of craniofacial V P . EID V A decreases across models as more covariates are included. The median genetic correlation estimate between each EID and body mass is 0.33. Analysis of the multivariate response to selection reveals that observed patterns of craniofacial variation in extant baboons cannot be attributed solely to correlated response to selection on body mass, particularly in males. Because a relatively large proportion of EID V A is shared with body mass variation, different methods of correcting for allometry by statistically controlling for size can alter residual V P patterns. This may conflate direct selection effects on craniofacial variation with those resulting from a correlated response to body mass selection. This shared genetic variation may partially explain how selection for increased body mass in two different papionin lineages produced remarkably similar craniofacial phenotypes. © 2017 Wiley Periodicals, Inc.

Flood, disaster, and turmoil: social issues in cleft and craniofacial care and crisis relief.

PubMed

Strauss, Ronald P; van Aalst, John A; Fox, Lynn; Stein, Margot; Moses, Michael; Cassell, Cynthia H

2011-11-01

To examine social issues in the conduct of cleft and craniofacial care through relief programs in disrupted crisis contexts. Social, health policy, and ethical analyses. At best, craniofacial team care is multidisciplinary, coordinated, and sustained, requiring a long-term relationship between team members, patients, and families. Disasters and societal turmoil interrupt such relationships, causing craniofacial care to become a secondary concern. Providing craniofacial team care in a crisis setting requires rebuilding disrupted coordination and communication. Crisis relief care involves a complex set of expectations and responsibilities and raises issues such as (1) quality assurance, infection control, appropriate standards of care, and follow-up care/continuity; (2) equity of access to services and clinical ethics in the context of war and/or deprivation; (3) training of visitors in the local nation or site; (4) disciplinary composition of teams, interprofessional communication/rivalry, and credentials of clinicians; (5) ownership of the site and local visitor relations; (6) fundraising and marketing strategies; and (7) ethical issues in the doctor-patient relationship. Specific ethical standards for international cleft and craniofacial care delivery also apply to domestic and global crisis relief contexts. Guidance on issues related to professional experience, informed consent, and continuity of care will help care providers address social and ethical issues raised in crisis relief programs. This paper proposes that the Position Paper of the American Cleft Palate-Craniofacial Association (ACPA) on International Treatment Programs should be used as a template to develop and disseminate a set of standards that apply to crisis relief.

Body Image and Quality of Life in Adolescents With Craniofacial Conditions

PubMed Central

Crerand, Canice E.; Sarwer, David B.; Kazak, Anne E.; Clarke, Alexandra; DPsych; Rumsey, Nichola

2017-01-01

Objective To evaluate body image in adolescents with and without craniofacial conditions; and to examine relationships between body image and quality of life. Design Case-control design. Setting A pediatric hospital’s craniofacial center and primary care practices. Participants 70 adolescents with visible craniofacial conditions and a demographically-matched sample of 42 adolescents without craniofacial conditions. Main Outcome Measure Adolescents completed measures of quality of life and body image including satisfaction with weight, facial and overall appearance; investment in appearance (importance of appearance to self-worth); and body image disturbance (appearance-related distress and impairment in functioning). Results Adolescents with craniofacial conditions reported lower appearance investment (p < 0.001) and were more likely to report concerns about facial features (p < 0.02) compared to non-affected youth. Females in both groups reported greater investment in appearance, greater body image disturbance, and lower weight satisfaction compared to males (p < 0.01). Within both groups, greater body image disturbance was associated with lower quality of life (p <0.01). The two groups did not differ significantly on measures of quality of life, body image disturbance, or satisfaction with appearance. Conclusions Body image and quality of life in adolescents with craniofacial conditions are similar to non-affected youth. Relationships between body image and quality of life emphasize that appearance perceptions are important to adolescents’ well-being regardless of whether they have a facial disfigurement. Investment in one’s appearance may explain variations in body image satisfaction and serve as an intervention target particularly for females. PMID:26751907

Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression.

PubMed

Quintana, Anita M; Geiger, Elizabeth A; Achilly, Nate; Rosenblatt, David S; Maclean, Kenneth N; Stabler, Sally P; Artinger, Kristin B; Appel, Bruce; Shaikh, Tamim H

2014-12-01

Mutations in HCFC1 (MIM300019), have been recently associated with cblX (MIM309541), an X-linked, recessive disorder characterized by multiple congenital anomalies including craniofacial abnormalities. HCFC1 is a transcriptional co-regulator that modulates the expression of numerous downstream target genes including MMACHC, but it is not clear how these HCFC1 targets play a role in the clinical manifestations of cblX. To begin to elucidate the mechanism by which HCFC1 modulates disease phenotypes, we have carried out loss of function analyses in the developing zebrafish. Of the two HCFC1 orthologs in zebrafish, hcfc1a and hcfc1b, the loss of hcfc1b specifically results in defects in craniofacial development. Subsequent analysis revealed that hcfc1b regulates cranial neural crest cell differentiation and proliferation within the posterior pharyngeal arches. Further, the hcfc1b-mediated craniofacial abnormalities were rescued by expression of human MMACHC, a downstream target of HCFC1 that is aberrantly expressed in cblX. Furthermore, we tested distinct human HCFC1 mutations for their role in craniofacial development and demonstrated variable effects on MMACHC expression in humans and craniofacial development in zebrafish. Notably, several individuals with mutations in either HCFC1 or MMACHC have been reported to have mild to moderate facial dysmorphia. Thus, our data demonstrates that HCFC1 plays a role in craniofacial development, which is in part mediated through the regulation of MMACHC expression. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between the curve of Spee and craniofacial variables: A regression analysis.

PubMed

Halimi, Abdelali; Benyahia, Hicham; Azeroual, Mohamed-Faouzi; Bahije, Loubna; Zaoui, Fatima

2018-06-01

The aim of this regression analysis was to identify the determining factors, which impact the curve of Spee during its genesis, its therapeutic reconstruction, and its stability, within a continuously evolving craniofacial morphology throughout life. We selected a total of 107 patients, according to the inclusion criteria. A morphological and functional clinical examination was performed for each patient: plaster models, tracing of the curve of Spee, crowding, Angle's classification, overjet and overbite were thus recorded. Then, we made a cephalometric analysis based on the standardized lateral cephalograms. In the sagittal dimension, we measured the values of angles ANB, SNA, SNB, SND, I/i; and the following distances: AoBo, I/NA, i/NB, SE and SL. In the vertical dimension, we measured the values of angles FMA, GoGn/SN, the occlusal plane, and the following distances: SAr, ArD, Ar/Con, Con/Gn, GoPo, HFP, HFA and IF. The statistical analysis was performed using the SPSS software with a significance level of 0.05. Our sample including 107 subjects was composed of 77 female patients (71.3%) and 30 male patients (27.8%) 7 hypodivergent patients (6.5%), 56 hyperdivergent patients (52.3%) and 44 normodivergent patients (41.1%). Patients' mean age was 19.35±5.95 years. The hypodivergent patients presented more pronounced curves of Spee compared to the normodivergent and the hyperdivergent populations; patients in skeletal Class I presented less pronounced curves of Spee compared to patients in skeletal Class II and Class III. These differences were non significant (P>0.05). The curve of Spee was positively and moderately correlated with Angle's classification, overjet, overbite, sellion-articulare distance, and breathing type (P<0.05). We found no correlation between age, gender and the other parameters included in the study with the curve of Spee (P>0.05). Seventy five percent (75%) of the hyperdivergent patients with an oral breathing presented an overbite of 3mm, which is quite excessive given the characteristics often admitted for this typology; this parameter could explain the overbite observed in the hyperdivergent population included in this study. For the multivariate analysis, the overbite and the sellion-articulare distance remained independently related to the curve of Spee according to the breathing type, Angle's classification, and overjet. This regression model explains 21.4% of the changes in the curve of Spee. Copyright © 2018. Published by Elsevier Masson SAS.

Morphological Integration of Soft-Tissue Facial Morphology in Down Syndrome and Siblings

PubMed Central

Starbuck, John; Reeves, Roger H.; Richtsmeier, Joan

2011-01-01

Down syndrome (DS), resulting from trisomy of chromosome 21, is the most common live-born human aneuploidy. The phenotypic expression of trisomy 21 produces variable, though characteristic, facial morphology. Although certain facial features have been documented quantitatively and qualitatively as characteristic of DS (e.g., epicanthic folds, macroglossia, and hypertelorism), all of these traits occur in other craniofacial conditions with an underlying genetic cause. We hypothesize that the typical DS face is integrated differently than the face of non-DS siblings, and that the pattern of morphological integration unique to individuals with DS will yield information about underlying developmental associations between facial regions. We statistically compared morphological integration patterns of immature DS faces (N = 53) with those of non-DS siblings (N = 54), aged 6–12 years using 31 distances estimated from 3D coordinate data representing 17 anthropometric landmarks recorded on 3D digital photographic images. Facial features are affected differentially in DS, as evidenced by statistically significant differences in integration both within and between facial regions. Our results suggest a differential affect of trisomy on facial prominences during craniofacial development. PMID:21996933

Morphological integration of soft-tissue facial morphology in Down Syndrome and siblings.

PubMed

Starbuck, John; Reeves, Roger H; Richtsmeier, Joan

2011-12-01

Down syndrome (DS), resulting from trisomy of chromosome 21, is the most common live-born human aneuploidy. The phenotypic expression of trisomy 21 produces variable, though characteristic, facial morphology. Although certain facial features have been documented quantitatively and qualitatively as characteristic of DS (e.g., epicanthic folds, macroglossia, and hypertelorism), all of these traits occur in other craniofacial conditions with an underlying genetic cause. We hypothesize that the typical DS face is integrated differently than the face of non-DS siblings, and that the pattern of morphological integration unique to individuals with DS will yield information about underlying developmental associations between facial regions. We statistically compared morphological integration patterns of immature DS faces (N = 53) with those of non-DS siblings (N = 54), aged 6-12 years using 31 distances estimated from 3D coordinate data representing 17 anthropometric landmarks recorded on 3D digital photographic images. Facial features are affected differentially in DS, as evidenced by statistically significant differences in integration both within and between facial regions. Our results suggest a differential affect of trisomy on facial prominences during craniofacial development. 2011 Wiley Periodicals, Inc.

[Anesthesia in a child operated for cleft lip associated with Patau's syndrome].

PubMed

Kamal, Manoj; Varghese, Don; Bhagde, Jeet; Singariya, Geeta; Simon, Annie Miju; Singh, Amar

Patients with Patau's syndrome (Trisomy 13) have multiple craniofacial, cardiac, neurological and renal anomalies with very less life expectancy. Among craniofacial anomalies cleft lip and palate are common. These craniofacial and cardiac anomalies present difficulties with anesthesia. We therefore describe the anesthetic management in the case of a Trisomy 13 child for operated for cleft lip at 10 months of age. Copyright © 2017. Publicado por Elsevier Editora Ltda.

Biomaterials in craniofacial reconstruction.

PubMed

Cho, Younghoon R; Gosain, Arun K

2004-07-01

Biomaterials have become an integral component of craniofacial reconstruction. Their increasing ease of use, long "shelf-life," and safety enables them to be used effectively and play an important role in reducing operating times. There are various biomaterials currently available and specific usages have been characterized well in the literature. This article reviews different biomaterials that can be used in craniofacial reconstruction,including autogenous bone, methyl methacrylate and hard tissue replacement,hydroxyapatite, porous polyethylene, bioactive glass, and demineralized bone.

American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection: Overview of a powerful tool for orthodontic research and teaching.

PubMed

Baumrind, Sheldon; Curry, Sean

2015-08-01

This article reports on the current status of the American Association of Orthodontists Foundation (AAOF) Craniofacial Growth Legacy Collection--an AAOF-supported multi-institutional project that uses the Internet and cloud computing to collect and share craniofacial images and data for orthodontic research and education. The project gives investigators and clinicians all over the world online access to longitudinal information on craniofacial development in untreated children with malocclusions of various types. It also is a unique source of control samples for testing the validity of consensually accepted beliefs about the effects of orthodontic treatment or of failure to treat. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Craniofacial reconstruction - series (image)

MedlinePlus

Patients requiring craniofacial reconstruction have: birth defects (such as hypertelorism, Crouzon's disease, Apert's syndrome) injuries to the head, face, or jaws (maxillofacial) tumors deformities caused by treatments of tumors

Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes

PubMed Central

de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

2016-01-01

Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1+/− mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies. PMID:27711076

Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.

PubMed

de Peralta, Mauro S Porcel; Mouguelar, Valeria S; Sdrigotti, María Antonella; Ishiy, Felipe A A; Fanganiello, Roberto D; Passos-Bueno, Maria R; Coux, Gabriela; Calcaterra, Nora B

2016-10-06

Treacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1 +/- mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROS-cytoprotective action that prevented the redox-responsive genes' upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

2014-09-01

Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

The FaceBase Consortium: A comprehensive program to facilitate craniofacial research

PubMed Central

Hochheiser, Harry; Aronow, Bruce J.; Artinger, Kristin; Beaty, Terri H.; Brinkley, James F.; Chai, Yang; Clouthier, David; Cunningham, Michael L.; Dixon, Michael; Donahue, Leah Rae; Fraser, Scott E.; Hallgrimsson, Benedikt; Iwata, Junichi; Klein, Ophir; Marazita, Mary L.; Murray, Jeffrey C.; Murray, Stephen; de Villena, Fernando Pardo-Manuel; Postlethwait, John; Potter, Steven; Shapiro, Linda; Spritz, Richard; Visel, Axel; Weinberg, Seth M.; Trainor, Paul A.

2012-01-01

The FaceBase Consortium consists of ten interlinked research and technology projects whose goal is to generate craniofacial research data and technology for use by the research community through a central data management and integrated bioinformatics hub. Funded by the National Institute of Dental and Craniofacial Research (NIDCR) and currently focused on studying the development of the middle region of the face, the Consortium will produce comprehensive datasets of global gene expression patterns, regulatory elements and sequencing; will generate anatomical and molecular atlases; will provide human normative facial data and other phenotypes; conduct follow up studies of a completed genome-wide association study; generate independent data on the genetics of craniofacial development, build repositories of animal models and of human samples and data for community access and analysis; and will develop software tools and animal models for analyzing and functionally testing and integrating these data. The FaceBase website (http://www.facebase.org) will serve as a web home for these efforts, providing interactive tools for exploring these datasets, together with discussion forums and other services to support and foster collaboration within the craniofacial research community. PMID:21458441

Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression

PubMed Central

Singh, Nikhil; Gupta, Mudit; Trivedi, Chinmay M.; Singh, Manvendra K.; Li, Li; Epstein, Jonathan A.

2013-01-01

Craniofacial development is characterized by reciprocal interactions between neural crest cells and neighboring cell populations of ectodermal, endodermal and mesodermal origin. Various genetic pathways play critical roles in coordinating the development of cranial structures by modulating the growth, survival and differentiation of neural crest cells. However, the regulation of these pathways, particularly at the epigenomic level, remains poorly understood. Using murine genetics, we show that neural crest cells exhibit a requirement for the class I histone deacetylase Hdac3 during craniofacial development. Mice in which Hdac3 has been conditionally deleted in neural crest demonstrate fully penetrant craniofacial abnormalities, including microcephaly, cleft secondary palate and dental hypoplasia. Consistent with these abnormalities, we observe dysregulation of cell cycle genes and increased apoptosis in neural crest structures in mutant embryos. Known regulators of cell cycle progression and apoptosis in neural crest, including Msx1, Msx2 and Bmp4, are upregulated in Hdac3-deficient cranial mesenchyme. These results suggest that Hdac3 serves as a critical regulator of craniofacial morphogenesis, in part by repressing core apoptotic pathways in cranial neural crest cells. PMID:23506836

The genesis of craniofacial biology as a health science discipline.

PubMed

Sperber, G H; Sperber, S M

2014-06-01

The craniofacial complex encapsulates the brain and contains the organs for key functions of the body, including sight, hearing and balance, smell, taste, respiration and mastication. All these systems are intimately integrated within the head. The combination of these diverse systems into a new field was dictated by the dental profession's desire for a research branch of basic science devoted and attuned to its specific needs. The traditional subjects of genetics, embryology, anatomy, physiology, biochemistry, dental materials, odontology, molecular biology and palaeoanthropology pertaining to dentistry have been drawn together by many newly emerging technologies. These new technologies include gene sequencing, CAT scanning, MRI imaging, laser scanning, image analysis, ultrasonography, spectroscopy and visualosonics. A vibrant unitary discipline of investigation, craniofacial biology, has emerged that builds on the original concept of 'oral biology' that began in the 1960s. This paper reviews some of the developments that have led to the genesis of craniofacial biology as a fully-fledged health science discipline of significance in the advancement of clinical dental practice. Some of the key figures and milestones in craniofacial biology are identified. © 2014 Australian Dental Association.

Aristaless-like homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats

PubMed Central

Lyons, Leslie A.; Erdman, Carolyn A.; Grahn, Robert A.; Hamilton, Michael J.; Carter, Michael J.; Helps, Christopher R.; Alhaddad, Hasan; Gandolfi, Barbara

2015-01-01

Frontonasal dysplasia (FND) can have severe presentations that are medically and socially debilitating. Several genes are implicated in FND conditions, including Aristaless-Like Homeobox 1 (ALX1), which is associated with FND3. Breeds of cats are selected and bred for extremes in craniofacial morphologies. In particular, a lineage of Burmese cats with severe brachycephyla is extremely popular and is termed Contemporary Burmese. Genetic studies demonstrated that the brachycephyla of the Contemporary Burmese is a simple co-dominant trait, however, the homozygous cats have a severe craniofacial defect that is incompatible with life. The craniofacial defect of the Burmese was genetically analyzed over a 20 year period, using various genetic analysis techniques. Family-based linkage analysis localized the trait to cat chromosome B4. Genome-wide association studies and other genetic analyses of SNP data refined a critical region. Sequence analysis identified a 12 bp in frame deletion in ALX1, c.496delCTCTCAGGACTG, which is 100% concordant with the craniofacial defect and not found in cats not related to the Contemporary Burmese. PMID:26610632

3D modeling, custom implants and its future perspectives in craniofacial surgery

PubMed Central

Parthasarathy, Jayanthi

2014-01-01

Custom implants for the reconstruction of craniofacial defects have gained importance due to better performance over their generic counterparts. This is due to the precise adaptation to the region of implantation, reduced surgical times and better cosmesis. Application of 3D modeling in craniofacial surgery is changing the way surgeons are planning surgeries and graphic designers are designing custom implants. Advances in manufacturing processes and ushering of additive manufacturing for direct production of implants has eliminated the constraints of shape, size and internal structure and mechanical properties making it possible for the fabrication of implants that conform to the physical and mechanical requirements of the region of implantation. This article will review recent trends in 3D modeling and custom implants in craniofacial reconstruction. PMID:24987592

Publication Rates of Studies Presented at the International Society of Craniofacial Surgery Congress.

PubMed

Dobson, Hannah; Wall, Steven

2016-11-01

The proportion of presentations achieving publication in a peer-review journal has been suggested to demonstrate the quality of research presented at a conference. No data is available examining the publication rate of research presented at Craniofacial Surgery meetings. The aim of the study was to examine the publication rate of abstracts presented at the International Society of Craniofacial Surgery Biennial Congresses from 2003 to 2011. A search was made of the PubMed database for publication of podium presentations of International Society of Craniofacial Surgery Congresses between 2003 and 2011. Thirty-five percent of podium presentations were published in a peer-reviewed journal. Thirty-one percent of presentations were published within 4 years, and the rate of publication decreased 2 years following presentation.

Injectable scaffolds: Preparation and application in dental and craniofacial regeneration

PubMed Central

Chang, Bei; Ahuja, Neelam; Ma, Chi; Liu, Xiaohua

2016-01-01

Injectable scaffolds are appealing for tissue regeneration because they offer many advantages over pre-formed scaffolds. This article provides a comprehensive review of the injectable scaffolds currently being investigated for dental and craniofacial tissue regeneration. First, we provide an overview of injectable scaffolding materials, including natural, synthetic, and composite biomaterials. Next, we discuss a variety of characteristic parameters and gelation mechanisms of the injectable scaffolds. The advanced injectable scaffolding systems developed in recent years are then illustrated. Furthermore, we summarize the applications of the injectable scaffolds for the regeneration of dental and craniofacial tissues that include pulp, dentin, periodontal ligament, temporomandibular joint, and alveolar bone. Finally, our perspectives on the injectable scaffolds for dental and craniofacial tissue regeneration are offered as signposts for the future advancement of this field. PMID:28649171

Craniofacial form and function in Metriorhynchidae (Crocodylomorpha: Thalattosuchia): modelling phenotypic evolution with maximum-likelihood methods.

PubMed

Young, Mark T; Bell, Mark A; Brusatte, Stephen L

2011-12-23

Metriorhynchid crocodylomorphs were the only group of archosaurs to fully adapt to a pelagic lifestyle. During the Jurassic and Early Cretaceous, this group diversified into a variety of ecological and morphological types, from large super-predators with a broad short snout and serrated teeth to specialized piscivores/teuthophages with an elongate tubular snout and uncarinated teeth. Here, we use an integrated repertoire of geometric morphometric (form), biomechanical finite-element analysis (FEA; function) and phylogenetic data to examine the nature of craniofacial evolution in this clade. FEA stress values significantly correlate with morphometric values representing skull length and breadth, indicating that form and function are associated. Maximum-likelihood methods, which assess which of several models of evolution best explain the distribution of form and function data on a phylogenetic tree, show that the two major metriorhynchid subclades underwent different evolutionary modes. In geosaurines, both form and function are best explained as evolving under 'random' Brownian motion, whereas in metriorhynchines, the form metrics are best explained as evolving under stasis and the function metric as undergoing a directional change (towards most efficient low-stress piscivory). This suggests that the two subclades were under different selection pressures, and that metriorhynchines with similar skull shape were driven to become functionally divergent.

Insulin alleviates degradation of skeletal muscle protein by inhibiting the ubiquitin-proteasome system in septic rats.

PubMed

Chen, Qiyi; Li, Ning; Zhu, Weiming; Li, Weiqin; Tang, Shaoqiu; Yu, Wenkui; Gao, Tao; Zhang, Juanjuan; Li, Jieshou

2011-06-03

Hypercatabolism is common under septic conditions. Skeletal muscle is the main target organ for hypercatabolism, and this phenomenon is a vital factor in the deterioration of recovery in septic patients. In skeletal muscle, activation of the ubiquitin-proteasome system plays an important role in hypercatabolism under septic status. Insulin is a vital anticatabolic hormone and previous evidence suggests that insulin administration inhibits various steps in the ubiquitin-proteasome system. However, whether insulin can alleviate the degradation of skeletal muscle protein by inhibiting the ubiquitin-proteasome system under septic condition is unclear. This paper confirmed that mRNA and protein levels of the ubiquitin-proteasome system were upregulated and molecular markers of skeletal muscle proteolysis (tyrosine and 3-methylhistidine) simultaneously increased in the skeletal muscle of septic rats. Septic rats were infused with insulin at a constant rate of 2.4 mU.kg-1.min-1 for 8 hours. Concentrations of mRNA and proteins of the ubiquitin-proteasome system and molecular markers of skeletal muscle proteolysis were mildly affected. When the insulin infusion dose increased to 4.8 mU.kg-1.min-1, mRNA for ubiquitin, E2-14 KDa, and the C2 subunit were all sharply downregulated. At the same time, the levels of ubiquitinated proteins, E2-14KDa, and the C2 subunit protein were significantly reduced. Tyrosine and 3-methylhistidine decreased significantly. We concluded that the ubiquitin-proteasome system is important skeletal muscle hypercatabolism in septic rats. Infusion of insulin can reverse the detrimental metabolism of skeletal muscle by inhibiting the ubiquitin-proteasome system, and the effect is proportional to the insulin infusion dose.

Melorheostosis involving the craniofacial skeleton.

PubMed

Ethunandan, Madanagopalan; Khosla, Nalin; Tilley, Elizabeth; Webb, Andrew

2004-11-01

Melorheostosis is a rare bone disorder, usually affecting the long bones and adjacent soft tissue. It was originally described by Leri and Joanny in 1922, after its classic x-ray features of flowing hyperostosis resembling dripping candle wax. There have been fewer than 10 reported cases of craniofacial involvement, and in most instances these have also involved the appendicular skeleton. The authors report a case of melorheostosis with isolated craniofacial involvement, describe the clinical course and radiologic and histologic features, and review the pertinent literature.

Development of an Ocular and Craniofacial Trauma Treatment Training System

DTIC Science & Technology

2013-08-01

Craniofacial Trauma Treatment Training System PRINCIPAL INVESTIGATOR: Mark P. Ottensmeyer, Ph.D. CONTRACTING ORGANIZATION: Massachusetts...Annual 3. DATES COVERED 11 July 2012 – 10 July 2013 4. TITLE AND SUBTITLE Development of an Ocular and Craniofacial Trauma Treatment Training System...15    Review of  treatment  modes and potential error modes to be detected ................... 15 2.3.2.a.   Implement  improvements  for  upgraded

Effect of hindlimb suspension and clenbuterol treatment on polyamine levels in skeletal muscle

NASA Technical Reports Server (NTRS)

Abukhalaf, Imad K.; von Deutsch, Daniel A.; Wineski, Lawrence E.; Silvestrov, Natalia A.; Abera, Saare A.; Sahlu, Sinafikish W.; Potter, David E.; Thierry-Palmer, M. (Principal Investigator)

2002-01-01

Polyamines are unbiquitous, naturally occurring small aliphatic, polycationic, endogenous compounds. They are involved in many cellular processes and may serve as secondary or tertiary messengers to hormonal regulation. The relationship of polyamines and skeletal muscle mass of adductor longus, extensor digitorum longus, and gastrocnemius under unloading (hindlimb suspension) conditions was investigated. Unloading significantly affected skeletal muscle polyamine levels in a fiber-type-specific fashion. Under loading conditions, clenbuterol treatment increased all polyamine levels, whereas under unloading conditions, only the spermidine levels were consistently increased. Unloading attenuated the anabolic effects of clenbuterol in predominately slow-twitch muscles (adductor longus), but had little impact on clenbuterol's action as a countermeasure in fast- twitch muscles such as the extensor digitorum longus. Spermidine appeared to be the primary polyamine involved in skeletal muscle atrophy/hypertrophy. Copyright 2002 S. Karger AG, Basel.

K-RasV14I recapitulates Noonan syndrome in mice

PubMed Central

Hernández-Porras, Isabel; Fabbiano, Salvatore; Schuhmacher, Alberto J.; Aicher, Alexandra; Cañamero, Marta; Cámara, Juan Antonio; Cussó, Lorena; Desco, Manuel; Heeschen, Christopher; Mulero, Francisca; Bustelo, Xosé R.; Guerra, Carmen; Barbacid, Mariano

2014-01-01

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. NS also is associated with a risk for developing myeloproliferative disorders (MPD), including juvenile myelomonocytic leukemia (JMML). Mutations responsible for NS occur in at least 11 different loci including KRAS. Here we describe a mouse model for NS induced by K-RasV14I, a recurrent KRAS mutation in NS patients. K-RasV14I–mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML. Homozygous animals had perinatal lethality whose penetrance varied with genetic background. Exposure of pregnant mothers to a MEK inhibitor rescued perinatal lethality and prevented craniofacial dysmorphia and cardiac defects. However, Mek inhibition was not sufficient to correct these defects when mice were treated after weaning. Interestingly, Mek inhibition did not correct the neoplastic MPD characteristic of these mutant mice, regardless of the timing at which the mice were treated, thus suggesting that MPD is driven by additional signaling pathways. These genetically engineered K-RasV14I–mutant mice offer an experimental tool for studying the molecular mechanisms underlying the clinical manifestations of NS. Perhaps more importantly, they should be useful as a preclinical model to test new therapies aimed at preventing or ameliorating those deficits associated with this syndrome. PMID:25359213

Association of transforming growth-factor alpha gene polymorphisms with nonsyndromic cleft palate only (CPO)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiang, R.; Lidral, A.C.; Ardinger, H.H.

1993-10-01

Genetic analysis and tissue-specific expression studies support a role for transforming growth-factor alpha (TGFA) in craniofacial development. Previous studies have confirmed an association of alleles for TGFA with nonsyndromic cleft lip with or without cleft palate (CL/P) in humans. The authors carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO). The PCR products from 12 overlapping sets of primers to the TGFA cDNA were examined by using single-strand conformational polymorphism analysis. Four DNA polymorphic sites for TGFA were identified in the 3[prime] untranslated region ofmore » the TGFA gene. These variants, as well as previously identified RFLPs for TGFA, were characterized in case and control populations for CPO by using X[sup 2] analysis. A significant association between alleles of TGFA and CPO was identified which further supports a role for this gene as one of the genetic determinants of craniofacial development. Sequence analysis of the variants disclosed a cluster of three variable sites within 30 bp of each other in the 3[prime] untranslated region previously associated with an antisense transcript. These studies extend the role for TGFA in craniofacial morphogenesis and support an interrelated mechanism underlying nonsyndromic forms of CL/P. 46 refs., 3 figs., 3 tabs.« less

Fishing the Molecular Bases of Treacher Collins Syndrome

PubMed Central

Weiner, Andrea M. J.; Scampoli, Nadia L.; Calcaterra, Nora B.

2012-01-01

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development. PMID:22295061

Fishing the molecular bases of Treacher Collins syndrome.

PubMed

Weiner, Andrea M J; Scampoli, Nadia L; Calcaterra, Nora B

2012-01-01

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

Craniofacial asymmetry as a marker of socioeconomic status among undocumented Mexican immigrants in the United States.

PubMed

Weisensee, Katherine E; Spradley, M Katherine

2018-05-01

This study examines levels of fluctuating asymmetry (FA) in Mexican residents, U.S. residents, and undocumented border crossers (UBCs) from Mexico to the United States. Craniofacial structures develop symmetrically under ideal circumstances; however, during periods of developmental stress random deviations from perfect symmetry, or FA, can occur. It is hypothesized that the UBC sample would represent individuals of a lower socioeconomic status (SES) who experienced higher stress levels during development, and that these individuals would consequently have higher levels of FA. Three-dimensional cranial landmarks were collected from 509 individuals representing the three resident groups. Geometric morphometric methods were used to calculate an FA score for each individual. The FA score provides a distance measure that is a scalar measure of the magnitude of FA in each individual. The results show that the difference in the means of the FA scores between UBCs and U.S. residents is 0.43 (p = 0.02), with UBCs showing significantly higher levels of FA compared to U.S. residents. Moreover, Mexican residents' FA levels are intermediate between and not significantly different from the other two samples. These results suggest that levels of FA may prove useful for reconstructing individuals' social and economic circumstances, and that craniofacial asymmetry provides a suitable biological marker for analyzing differences in SES among different groups. Copyright © 2018 Elsevier B.V. All rights reserved.

Regenerating skeletal muscle in the face of aging and disease.

PubMed

Jasuja, Ravi; LeBrasseur, Nathan K

2014-11-01

Skeletal muscle is a fundamental organ in the generation of force and movement, the regulation of whole-body metabolism, and the provision of resiliency. Indeed, physical medicine and rehabilitation is recognized for optimizing skeletal muscle health in the context of aging (sarcopenia) and disease (cachexia). Exercise is, and will remain, the cornerstone of therapies to improve skeletal muscle health. However, there are now a number of promising biologic and small molecule interventions currently under development to rejuvenate skeletal muscle, including myostatin inhibitors, selective androgen receptor modulators, and an activator of the fast skeletal muscle troponin complex. The opportunities for skeletal muscle-based regenerative therapies and a selection of emerging pharmacologic interventions are discussed in this review.

Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle

PubMed Central

Vendelbo, M. H.; Clasen, B. F. F.; Treebak, J. T.; Møller, L.; Krusenstjerna-Hafstrøm, T.; Madsen, M.; Nielsen, T. S.; Stødkilde-Jørgensen, H.; Pedersen, S. B.; Jørgensen, J. O. L.; Goodyear, L. J.; Wojtaszewski, J. F. P.; Møller, N.

2012-01-01

During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated eight healthy subjects after a 72-h fast compared with a 10-h overnight fast. Insulin action on skeletal muscle was assessed by a hyperinsulinemic euglycemic clamp and by determining insulin signaling to glucose transport. In addition, substrate oxidation, skeletal muscle lipid content, regulation of glycogen synthesis, and AMPK signaling were assessed. Skeletal muscle insulin sensitivity was reduced profoundly in response to a 72-h fast and substrate oxidation shifted to predominantly lipid oxidation. This was associated with accumulation of both lipid and glycogen in skeletal muscle. Intracellular insulin signaling to glucose transport was impaired by regulation of phosphorylation at specific sites on AS160 but not TBC1D1, both key regulators of glucose uptake. In contrast, fasting did not impact phosphorylation of AMPK or insulin regulation of Akt, both of which are established upstream kinases of AS160. These findings show that insulin resistance in muscles from healthy individuals is associated with suppression of site-specific phosphorylation of AS160, without Akt or AMPK being affected. This impairment of AS160 phosphorylation, in combination with glycogen accumulation and increased intramuscular lipid content, may provide the underlying mechanisms for resistance to insulin in skeletal muscle after a prolonged fast. PMID:22028408

Brief communication: timing of spheno-occipital closure in modern Western Australians.

PubMed

Franklin, Daniel; Flavel, Ambika

2014-01-01

The spheno-occipital synchondrosis is a craniofacial growth centre between the occipital and sphenoid bones-its ossification persists into adolescence, which for the skeletal biologist, means it has potential application for estimating subadult age. Based on previous research the timing of spheno-occipital fusion is widely variable between and within populations, with reports of complete fusion in individuals as young as 11 years of age and nonfusion in adults. The aim of this study is, therefore, to examine this structure in a mixed sex sample of Western Australian individuals that developmentally span late childhood to adulthood. The objective is to develop statistically quantified age estimation standards based on scoring the degree of spheno-occipital fusion. The sample comprises multidetector computed tomography (MDCT) scans of 312 individuals (169 male; 143 female) between 5 and 25 years of age. Each MDCT scan is visualized in a standardized sagittal plane using three-dimensional oblique multiplanar reformatting. Fusion status is scored according to a four-stage system. Transition analysis is used to calculate age ranges for each defined stage and determine the mean age for transition between an unfused, fusing and fused status. The maximum likelihood estimates for the transition from open to fusing in the endocranial half is 14.44 years (male) and 11.42 years (female); transition from fusion in the ectocranial half to complete fusion is 16.16 years (male) and 13.62 years (female). This study affirms the potential value of assessing the degree of fusion in the spheno-occipital synchondrosis as an indicator of skeletal age. Copyright © 2013 Wiley Periodicals, Inc.

Cranial airways and the integration between the inner and outer facial skeleton in humans.

PubMed

Bastir, Markus; Rosas, Antonio

2013-10-01

The cranial airways are in the center of the human face. Therefore variation in the size and shape of these central craniofacial structures could have important consequences for the surrounding midfacial morphology during development and evolution. Yet such interactions are unclear because one school of thought, based on experimental and developmental evidence, suggests a relative independence (modularity) of these two facial compartments, whereas another one assumes tight morphological integration. This study uses geometric morphometrics of modern humans (N = 263) and 40 three-dimensional-landmarks of the skeletal nasopharynx and nasal cavity and outer midfacial skeleton to analyze these questions in terms of modularity. The sizes of all facial compartments were all strongly correlated. Shape integration was high between the cranial airways and the outer midfacial skeleton and between the latter and the anterior airway openings (skeletal regions close to and including piriform aperture). However, no shape integration was detected between outer midface and posterior airway openings (nasopharynx and choanae). Similarly, no integration was detected between posterior and anterior airway openings. This may reflect functional modularization of nasal cavity compartments related to respiratory physiology and differential developmental interactions with the face. Airway size likely relates to the energetics of the organism, whereas airways shape might be more indicative of respiratory physiology and climate. Although this hypothesis should be addressed in future steps, here we suggest that selection on morphofunctional characteristics of the cranial airways could have cascading effects for the variation, development, and evolution of the human face. Copyright © 2013 Wiley Periodicals, Inc.

Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

PubMed

Davideau, J L; Demri, P; Hotton, D; Gu, T T; MacDougall, M; Sharpe, P; Forest, N; Berdal, A

1999-12-01

Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

Characterizing mandibular growth using three-dimensional imaging techniques and anatomic landmarks

PubMed Central

Kelly, Michael P.; Vorperian, Houri K.; Wang, Yuan; Tillman, Katelyn K.; Werner, Helen M.; Chung, Moo K.; Gentry, Lindell R.

2017-01-01

Objective To provide quantitative data on the multi-planar growth of the mandible, this study derived accurate linear and angular mandible measurements using landmarks on three dimensional (3D) mandible models. This novel method was used to quantify 3D mandibular growth and characterize the emergence of sexual dimorphism. Design Cross-sectional and longitudinal imaging data were obtained from a retrospective computed tomography (CT) database for 51 typically developing individuals between the ages of one and nineteen years. The software Analyze was used to generate 104 3DCT mandible models. Eleven landmarks placed on the models defined six linear measurements (lateral condyle, gonion, and endomolare width, ramus and mental depth, and mandible length) and three angular measurements (gonion, gnathion, and lingual). A fourth degree polynomial fit quantified growth trends, its derivative quantified growth rates, and a composite growth model determined growth types (neural/cranial and somatic/skeletal). Sex differences were assessed in four age cohorts, each spanning five years, to determine the ontogenetic pattern producing sexual dimorphism of the adult mandible. Results Mandibular growth trends and growth rates were non-uniform. In general, structures in the horizontal plane displayed predominantly neural/cranial growth types, whereas structures in the vertical plane had somatic/skeletal growth types. Significant prepubertal sex differences in the inferior aspect of the mandible dissipated when growth in males began to outpace that of females at eight to ten years of age, but sexual dimorphism re-emerged during and after puberty. Conclusions This 3D analysis of mandibular growth provides preliminary normative developmental data for clinical assessment and craniofacial growth studies. PMID:28161602

Disruption of RAB40AL function leads to Martin--Probst syndrome, a rare X-linked multisystem neurodevelopmental human disorder.

PubMed

Bedoyan, Jirair Krikor; Schaibley, Valerie M; Peng, Weiping; Bai, Yongsheng; Mondal, Kajari; Shetty, Amol C; Durham, Mark; Micucci, Joseph A; Dhiraaj, Arti; Skidmore, Jennifer M; Kaplan, Julie B; Skinner, Cindy; Schwartz, Charles E; Antonellis, Anthony; Zwick, Michael E; Cavalcoli, James D; Li, Jun Z; Martin, Donna M

2012-05-01

Martin--Probst syndrome (MPS) is a rare X-linked disorder characterised by deafness, cognitive impairment, short stature and distinct craniofacial dysmorphisms, among other features. The authors sought to identify the causative mutation for MPS. Massively parallel sequencing in two affected, related male subjects with MPS identified a RAB40AL (also called RLGP) missense mutation (chrX:102,079,078-102,079,079AC→GA p.D59G; hg18). RAB40AL encodes a small Ras-like GTPase protein with one suppressor of cytokine signalling box. The p.D59G variant is located in a highly conserved region of the GTPase domain between β-2 and β-3 strands. Using RT-PCR, the authors show that RAB40AL is expressed in human fetal and adult brain and kidney, and adult lung, heart, liver and skeletal muscle. RAB40AL appears to be a primate innovation, with no orthologues found in mouse, Xenopus or zebrafish. Western analysis and fluorescence microscopy of GFP-tagged RAB40AL constructs from transiently transfected COS7 cells show that the D59G missense change renders RAB40AL unstable and disrupts its cytoplasmic localisation. This is the first study to show that mutation of RAB40AL is associated with a human disorder. Identification of RAB40AL as the gene mutated in MPS allows for further investigations into the molecular mechanism(s) of RAB40AL and its roles in diverse processes such as cognition, hearing and skeletal development.

Disruption of RAB40AL function leads to Martin–Probst syndrome, a rare X-linked multisystem neurodevelopmental human disorder

PubMed Central

Bedoyan, Jirair Krikor; Schaibley, Valerie M; Peng, Weiping; Bai, Yongsheng; Mondal, Kajari; Shetty, Amol C; Durham, Mark; Micucci, Joseph A; Dhiraaj, Arti; Skidmore, Jennifer M; Kaplan, Julie B; Skinner, Cindy; Schwartz, Charles E; Antonellis, Anthony; Zwick, Michael E; Cavalcoli, James D; Li, Jun Z

2012-01-01

Background and aim Martin–Probst syndrome (MPS) is a rare X-linked disorder characterised by deafness, cognitive impairment, short stature and distinct craniofacial dysmorphisms, among other features. The authors sought to identify the causative mutation for MPS. Methods and results Massively parallel sequencing in two affected, related male subjects with MPS identified a RAB40AL (also called RLGP) missense mutation (chrX:102,079,078-102,079,079AC→GA p.D59G; hg18). RAB40AL encodes a small Ras-like GTPase protein with one suppressor of cytokine signalling box. The p.D59G variant is located in a highly conserved region of the GTPase domain between β-2 and β-3 strands. Using RT-PCR, the authors show that RAB40AL is expressed in human fetal and adult brain and kidney, and adult lung, heart, liver and skeletal muscle. RAB40AL appears to be a primate innovation, with no orthologues found in mouse, Xenopus or zebrafish. Western analysis and fluorescence microscopy of GFP-tagged RAB40AL constructs from transiently transfected COS7 cells show that the D59G missense change renders RAB40AL unstable and disrupts its cytoplasmic localisation. Conclusions This is the first study to show that mutation of RAB40AL is associated with a human disorder. Identification of RAB40AL as the gene mutated in MPS allows for further investigations into the molecular mechanism(s) of RAB40AL and its roles in diverse processes such as cognition, hearing and skeletal development. PMID:22581972

Siamese twins with craniofacial duplication and bilateral cleft lip/palate in a ceramic representation of the Chimú culture (Peru): a comparative analysis with a current case.

PubMed

Pachajoa, Harry; Hernandez-Amaris, Maria F; Porras-Hurtado, Gloria Liliana; Rodriguez, Carlos A

2014-06-01

Craniofacial duplication or diprosopus is a very rare malformation that is present in approximately 0.4% of conjoined twins. Here is presented a case of craniofacial duplication in association with bilateral cleft lip/palate in both heads found in a ceramic representation from the early Chimú culture from Peru. A comparative analysis is made with a current case of a 28-week-old fetus with similar characteristics. After reviewing the medical literature on conjoined twins, very few reports of facial cleft in both twins were found, with no reports at all of bilateral cleft lip/palate. This ceramic crock is considered one of the first representations suggestive of craniofacial duplication, and probably the first reporting it in association with facial cleft.

Dental and Nondental Stem Cell Based Regeneration of the Craniofacial Region: A Tissue Based Approach

PubMed Central

Hughes, Declan; Song, Bing

2016-01-01

Craniofacial reconstruction may be a necessary treatment for those who have been affected by trauma, disease, or pathological developmental conditions. The use of stem cell therapy and tissue engineering shows massive potential as a future treatment modality. Currently in the literature, there is a wide variety of published experimental studies utilising the different stem cell types available and the plethora of available scaffold materials. This review investigates different stem cell sources and their unique characteristics to suggest an ideal cell source for regeneration of individual craniofacial tissues. At present, understanding and clinical applications of stem cell therapy remain in their infancy with numerous challenges to overcome. In spite of this, the field displays immense capacity and will no doubt be utilised in future clinical treatments of craniofacial regeneration. PMID:27143979

Oral and Craniofacial Clinical Signs Associated to Genetic Conditions in Human Identification Part I: A Review

PubMed Central

Ayoub, Fouad; Aoun, Nicole; el Husseini, Hassan; Jassar, Houssam; Sayah, Fida; Salameh, Ziad

2015-01-01

Background: Forensic dentistry is one of the most reliable methods used in human identification when other technique as fingerprint, DNA, visual identification cannot be used. Genetic disorders have several manifestations that can target the intra-oral cavity, the cranio-facial area or any location in the human body. Materials and Methods: A literature search of the scientific database (Medline and Science Direct) for the years 1990 to 2014 was carried out to find out all the available papers that indicate oral, cranio-facial signs, genetic and human identification. Results: A table with 10 genetic conditions was described with oral and cranio-facial signs that can help forensic specialist in human identification. Conclusion: This review showed a correlation between genetics, facial and intra-oral signs that would help forensic ondontologist in the identification procedures. PMID:26028912

Management options of non-syndromic sagittal craniosynostosis.

PubMed

Lee, Bryan S; Hwang, Lee S; Doumit, Gaby D; Wooley, Joseph; Papay, Francis A; Luciano, Mark G; Recinos, Violette M

2017-05-01

There have been various effective surgical procedures for the treatment of non-syndromic sagittal craniosynostosis, but no definitive guidelines for management have been established. We conducted a study to elucidate the current state of practice and establish a warranted standard of care. An Internet-based study was sent to 180 pediatric neurosurgeons across the country and 102 craniofacial plastic surgeons in fourteen different countries, to collect data for primary indication for surgical management, preference for timing and choice of surgery, and pre-, peri-, and post-operative management options. The overall response rate from both groups was 32% (n=90/284). Skull deformity was the primary indication for surgical treatment in patients without signs of hydrocephalus for both neurosurgeons and craniofacial surgeons (80% and 63%, respectively). Open surgical management was most commonly performed at six months of age by neurosurgeons (46%) and also by craniofacial surgeons (35%). Open surgical approach was favored for patients younger than four months of age by neurosurgeons (50%), but endoscopic approach was favored by craniofacial surgeons (35%). When performing an open surgical intervention, most neurosurgeons preferred pi or reversed pi procedure (27%), whereas total cranial vault remodeling was the most commonly performed procedure by craniofacial surgeons (37%). The data demonstrated a discrepancy in the treatment options for non-syndromic sagittal craniosynostosis. By conducting/comparing a wide survey to collect consolidative data from both groups of pediatric neurosurgeons and craniofacial plastic surgeons, we can attempt to facilitate the establishment of standard of care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi-detector row computed tomography.

PubMed

Takahashi, Masashi; Ohashi, Hirofumi

2013-06-01

Costello syndrome is a rare multiple congenital anomaly syndrome caused by heterozygous germline HRAS mutations, which is characterized by intellectual disability, growth retardation, distinctive facies, loose skin, cardiomyopathy and a preposition to malignancies. Although teeth abnormalities have been encountered in nearly two-thirds of the patients in literature, the evaluation tended to be limited to the extent which can be obtained from physical examination. We investigated detailed craniofacial, oral and dental findings in four patients with Costello syndrome. In this study, images reconstructed by multi-detector row computed tomography (MDCT) were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. All four patients showed true/relative macrocephaly with facial bone hypoplasia and gingival hypertrophy. Occlusal attrition, malocclusion, small dental arches, microdontia, and convex face were noted in three patients. In addition, one patient showed dental caries, conic tooth and gingivitis, and another patient showed hypodontia. Our study suggests that craniofacial and dental abnormalities are common in Costello syndrome patients and comprehensive dental care should be provided from early infancy. To our knowledge, this is the first study of thorough craniofacial and dental evaluation by using MDCT in Costello syndrome. MDCT is a useful tool for precise evaluation of craniofacial and oral manifestations in patients with congenital anomaly/intellectual disability syndromes. © 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.

Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

PubMed

Crist, Colin

2017-01-01

Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mouse Models of Rare Craniofacial Disorders.

PubMed

Achilleos, Annita; Trainor, Paul A

2015-01-01

A rare disease is defined as a condition that affects less than 1 in 2000 individuals. Currently more than 7000 rare diseases have been documented, and most are thought to be of genetic origin. Rare diseases primarily affect children, and congenital craniofacial syndromes and disorders constitute a significant proportion of rare diseases, with over 700 having been described to date. Modeling craniofacial disorders in animal models has been instrumental in uncovering the etiology and pathogenesis of numerous conditions and in some cases has even led to potential therapeutic avenues for their prevention. In this chapter, we focus primarily on two general classes of rare disorders, ribosomopathies and ciliopathies, and the surprising finding that the disruption of fundamental, global processes can result in tissue-specific craniofacial defects. In addition, we discuss recent advances in understanding the pathogenesis of an extremely rare and specific craniofacial condition known as syngnathia, based on the first mouse models for this condition. Approximately 1% of all babies are born with a minor or major developmental anomaly, and individuals suffering from rare diseases deserve the same quality of treatment and care and attention to their disease as other patients. © 2015 Elsevier Inc. All rights reserved.

Bone Repair Cells for Craniofacial Regeneration

PubMed Central

Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

2012-01-01

Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

The FaceBase Consortium: a comprehensive resource for craniofacial researchers

PubMed Central

Brinkley, James F.; Fisher, Shannon; Harris, Matthew P.; Holmes, Greg; Hooper, Joan E.; Wang Jabs, Ethylin; Jones, Kenneth L.; Kesselman, Carl; Klein, Ophir D.; Maas, Richard L.; Marazita, Mary L.; Selleri, Licia; Spritz, Richard A.; van Bakel, Harm; Visel, Axel; Williams, Trevor J.; Wysocka, Joanna

2016-01-01

The FaceBase Consortium, funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health, is designed to accelerate understanding of craniofacial developmental biology by generating comprehensive data resources to empower the research community, exploring high-throughput technology, fostering new scientific collaborations among researchers and human/computer interactions, facilitating hypothesis-driven research and translating science into improved health care to benefit patients. The resources generated by the FaceBase projects include a number of dynamic imaging modalities, genome-wide association studies, software tools for analyzing human facial abnormalities, detailed phenotyping, anatomical and molecular atlases, global and specific gene expression patterns, and transcriptional profiling over the course of embryonic and postnatal development in animal models and humans. The integrated data visualization tools, faceted search infrastructure, and curation provided by the FaceBase Hub offer flexible and intuitive ways to interact with these multidisciplinary data. In parallel, the datasets also offer unique opportunities for new collaborations and training for researchers coming into the field of craniofacial studies. Here, we highlight the focus of each spoke project and the integration of datasets contributed by the spokes to facilitate craniofacial research. PMID:27287806

Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression.

PubMed

Singh, Nikhil; Gupta, Mudit; Trivedi, Chinmay M; Singh, Manvendra K; Li, Li; Epstein, Jonathan A

2013-05-15

Craniofacial development is characterized by reciprocal interactions between neural crest cells and neighboring cell populations of ectodermal, endodermal and mesodermal origin. Various genetic pathways play critical roles in coordinating the development of cranial structures by modulating the growth, survival and differentiation of neural crest cells. However, the regulation of these pathways, particularly at the epigenomic level, remains poorly understood. Using murine genetics, we show that neural crest cells exhibit a requirement for the class I histone deacetylase Hdac3 during craniofacial development. Mice in which Hdac3 has been conditionally deleted in neural crest demonstrate fully penetrant craniofacial abnormalities, including microcephaly, cleft secondary palate and dental hypoplasia. Consistent with these abnormalities, we observe dysregulation of cell cycle genes and increased apoptosis in neural crest structures in mutant embryos. Known regulators of cell cycle progression and apoptosis in neural crest, including Msx1, Msx2 and Bmp4, are upregulated in Hdac3-deficient cranial mesenchyme. These results suggest that Hdac3 serves as a critical regulator of craniofacial morphogenesis, in part by repressing core apoptotic pathways in cranial neural crest cells. Copyright © 2013 Elsevier Inc. All rights reserved.

[Anterior craniofacial resection: oncologic outcome and complications in a series of 111 cases].

PubMed

Suárez, C; Llorente, J L; Fernández de León, R; Cabanillas, R; Suárez, V; López, A

2004-01-01

Anterior craniofacial resection is a standardized procedure for the treatment of ethmoid and frontal orbital tumors with intracranial invasion. A retrospective review of 111 patients with sinonasal tumors involving the anterior skull base who underwent combined craniofacial surgery. The most frequent pathological entity was adenocarcinoma (54 cases) and other epithelial tumors (29 cases). Five year actuarial survival according to the Kaplan-Meier method was 40%. Survival was affected by the histology of the tumor, brain involvement, and deep soft tissue involvement of the orbit. The UICC staging system did not show statistical prognostic significance. Complications occurred in 39 (35.1%) patients, resulting in 4 (3.6%) postoperative deaths. Major complications included cerebrospinal fluid leak in 18 patients, meningitis in 10, infection in 9, stroke in 4, and pneumocephalus in 4. The extent of the craniofacial resection was the most important factor associated with major complications. Despite the advanced stage of most of the patients, anterior craniofacial resection succeeded in terms of an acceptable survival rate. Nevertheless, significant complications were observed although in most patients were not life-threatening and had no negative impact on the quality of life.

Bone Grafting the Cleft Maxilla

MedlinePlus

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The fourth dimension in simulation surgery for craniofacial surgical procedures.

PubMed

Kurihara, T

2001-03-01

The intracranial volume was measured in all 18 cases of craniosynostosis and craniofacial synostosis with 3DCT using a modification of Miyake's formula, with a 6 years' follow-up. 1: There were no cases where the intracranial volume was less than the modified Miyake's formula. 2: Total cranial reshaping, compared to the local forehead advancement, was effective in increasing the intracranial cavity and growth postoperatively. 3: In cases of craniofacial synostosis, there is a possibility that mental retardation will develop if the intracranial volume tends to increase rapidly and more than expected.

Differences in Craniofacial Structures and Obesity in Caucasian and Chinese Patients with Obstructive Sleep Apnea

PubMed Central

Lee, Richard W. W.; Vasudavan, Sivabalan; Hui, David S.; Prvan, Tania; Petocz, Peter; Darendeliler, M. Ali; Cistulli, Peter A.

2010-01-01

Study Objectives: To explore differences in craniofacial structures and obesity between Caucasian and Chinese patients with obstructive sleep apnea (OSA). Design: Inter-ethnic comparison study. Setting: Two sleep disorder clinics in Australia and Hong Kong. Patients: 150 patients with OSA (74 Caucasian, 76 Chinese). Interventions: Anthropometry, cephalometry, and polysomnography were performed and compared. Subgroup analyses after matching for: (1) body mass index (BMI); (2) OSA severity. Measurements and Results: The mean age and BMI were similar between the ethnic groups. Chinese patients had more severe OSA (AHI 35.3 vs 25.2 events/h, P = 0.005). They also had more craniofacial bony restriction, including a shorter cranial base (63.6 ± 3.3 vs 77.5 ± 6.7 mm, P < 0.001), maxilla (50.7 ± 3.7 vs 58.8 ± 4.3 mm, P < 0.001) and mandible length (65.4 ± 4.2 vs 77.9 ± 9.4 mm, P < 0.001). These findings remained after correction for differences in body height. Similar results were shown in the BMI-matched analysis (n = 66). When matched for OSA severity (n = 52), Chinese patients had more craniofacial bony restriction, but Caucasian patients were more overweight (BMI 30.7 vs 28.4 kg/m2, P = 0.03) and had a larger neck circumference (40.8 vs 39.1 cm, P = 0.004); however, the ratios of BMI to the mandible or maxilla size were similar. Conclusions: Craniofacial factors and obesity contribute differentially to OSA in Caucasian and Chinese patients. For the same degree of OSA severity, Caucasians were more overweight, whereas Chinese exhibited more craniofacial bony restriction. Citation: Lee RWW; Vasudavan S; Hui DS; Prvan T; Petocz P; Darendeliler MA; Cistulli PA. Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. SLEEP 2010;33(8):1075-1080. PMID:20815189

Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.

1988-11-01

Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plugmore » or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.« less

Novel autosomal dominant mandibulofacial dysostosis with ptosis: clinical description and exclusion of TCOF1

PubMed Central

Hedera, P; Toriello, H; Petty, E

2002-01-01

Methods: Six affected family members underwent a complete medical genetics physical examination and two affected subjects had skeletal survey. All available medical records were reviewed. Linkage analysis using the markers spanning the TCOF1 locus was performed. One typically affected family member had a high resolution karyotype. Results: Affected subjects had significant craniofacial abnormalities without any significant acral changes and thus had a phenotype consistent with a MFD variant. Distinctive features included hypoplasia of the zygomatic complex, micrognathia with malocclusion, auricular abnormalities with conductive hearing loss, and ptosis. Significantly negative two point lod scores were obtained for markers spanning the TCOF1 locus, excluding the possibility that the disease in our kindred is allelic with TCS. High resolution karyotype was normal. Conclusions: We report a kindred with a novel type of MFD that is not linked to the TCOF1 locus and is also clinically distinct from other types of AD MFD. Identification of additional families will facilitate identification of the gene causing this type of AD MFD and further characterisation of the clinical phenotype. PMID:12114479

Say-Meyer syndrome: additional manifestations in a new patient and phenotypic assessment.

PubMed

Salinas-Torres, Victor M

2015-07-01

In 1981, Say and Meyer described a seemingly X-linked recessive syndrome of trigonocephaly, short stature, and developmental delay. Here, I present a new patient and review eight patients from the literature examining the nature and phenotypic differences. A Mexican 10-year-old boy with Say-Meyer syndrome is described. Additionally, he had C6 vertebral right pedicle agenesis, brachymesophalangy of the fifth fingers, bilateral widening of Sylvian fissure, and white matter amplitude as novel observed findings of the syndrome. This appears to be the first Say-Meyer syndrome patient with extracranial skeletal anomalies. In light of these manifestations, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with a significant clinical variability. Moreover, increasing evidence points to a variable expressivity of the same autosomal dominant mutation. Accordingly, it is proposed that Say-Meyer syndrome should be considered in those patients with the combination of trigonocephaly/metopic synostosis, short stature, developmental delay including prenatal and postnatal growth disorders, craniofacial dysmorphic features (especially hypotelorism), structural CNS anomalies (mainly white matter involvement), conductive hearing loss, seizures, and cardiovascular abnormalities.

Unmasking of a Recessive SCARF2 Mutation by a 22q11.12 de novo Deletion in a Patient with Van den Ende-Gupta Syndrome.

PubMed

Bedeschi, M F; Colombo, L; Mari, F; Hofmann, K; Rauch, A; Gentilin, B; Renieri, A; Clerici, D

2010-01-01

Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation.

Simpson-Golabi-Behmel syndrome associated with renal dysplasia and embryonal tumor: localization of the gene to Xqcen-q21.

PubMed

Hughes-Benzie, R M; Hunter, A G; Allanson, J E; Mackenzie, A E

We report 6 affected males in a 5-generation family with x-linked Simpson-Golabi-Behmel (SGB) syndrome. All had pre- and postnatal overgrowth with 2 adult males attaining heights over 195 cm. Other features included "coarse" face with hypertelorism, broad nasal root, cleft palate, full lips with a midline groove of the lower lip, grooved tongue with tongue tie, prominent mandible, congenital heart defects, arrhythmias, supernumerary nipples, splenomegaly, large dysplastic kidneys, cryptorchidism, hypospadias, skeletal abnormalities and postaxial hexadactyly. All affected individuals were of normal intelligence. One boy died at age 19 months of a neuroblastoma. The putative origin of the gene in this family was the maternal great grandmother of the propositus. Eight carrier females, who showed varying manifestations of the gene, have been identified. Anthropometric analysis has identified preliminary characteristic craniofacial dimensions in this syndrome. Molecular studies have shown a maximal lod score of 2.81 with no recombinants observed for the SGB-DXYS68 pairing, mapping the disorder to Xqcen-Xq21.3.

Obstetric significance of fetal craniofacial duplication. A case report.

PubMed

Chervenak, F A; Pinto, M M; Heller, C I; Norooz, H

1985-01-01

Craniofacial duplication (diprosopus) is a rare form of conjoined twins. Whenever fetal hydrocephalus is diagnosed, a careful search for other anomalies, such as diprosopus, is mandatory. The obstetric management depends upon the time of the diagnosis.

77 FR 35990 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... Craniofacial Research Special Emphasis Panel; Molecular Characterization of Salivary Tumors RFA: R01 and R21...: Jayalakshmi Raman, Ph.D., Scientific Review Officer, Scientific Review Branch, National Institute of Dental...

Clinical application of three-dimensional printing technology in craniofacial plastic surgery.

PubMed

Choi, Jong Woo; Kim, Namkug

2015-05-01

Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models.

The craniofacial complex in 47, XXX females.

PubMed

Krusinskiene, Viktorija; Krusinskie, Viktorija; Alvesalo, Lassi; Sidlauskas, Antanas

2005-08-01

A study of the craniofacial complex in four 47, XXX Finnish females, or females with an extra X chromosome, was carried out using cephalometric analysis comprising linear and angular measurements. The lengths of the anterior and posterior cranial bases, the calvarium, mandibular ramus and posterior and upper anterior face heights were found to be significantly shorter than in female controls, while the angles between the foraminal and clival planes, the mandibular plane and cranial base, the maxillary and occlusal planes, the maxillary and mandibular planes and the foraminal and mandibular planes, and also the gonial angle, were significantly enlarged. The present findings of reduced linear measurements, together with the results of studies on the craniofacial complex of 47, XXY and 47, XYY males, suggest dimensional variation between these groups from the promoting effect of an extra Y chromosome and the retarding effect of an extra X chromosome on craniofacial growth.

Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation

PubMed Central

Kong, Yawei; Grimaldi, Michael; Curtin, Eugene; Dougherty, Max; Kaufman, Charles; White, Richard M.; Zon, Leonard I.; Liao, Eric C.

2015-01-01

Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor TRIM abrogated first pharyngeal arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with over-expression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complimentary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation and convergence during craniofacial morphogenesis. PMID:24684905

Clinical Application of Three-Dimensional Printing Technology in Craniofacial Plastic Surgery

PubMed Central

Kim, Namkug

2015-01-01

Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models. PMID:26015880

Growth and Development of Dentofacial Complex influenced by Genetic and Environmental Factors using Monozygotic Twins.

PubMed

Manjusha, K K; Jyothindrakumar, K; Nishad, A; Manoj, K Madhav

2017-09-01

The purpose of this study was to determine the possible effects of genetic and environmental factors on dentofacial complex using monozygotic twins. The study sample was made of 21 pairs of monozygotic twins (14 female pairs and seven male pairs) between 10 and 25 years. Pretreatment lateral cephalo-grams were used which were traced and digitized, and various landmarks to determine the anteroposterior and vertical proportions were marked. Samples were divided into two groups. The correlation between groups was found by calculating Pearson's product moment correlation coefficients. The range of the correlation coefficient was from 0.705 to 0.952. Gonial angle showed the highest correlation coefficient (0.952), while saddle angle showed the lowest correlation coefficient (0.705). The growth and development of craniofacial complex is under mutifactorial control. However, genetic influences do tend to play a dominant role. By studying identical twins, we can study about the interaction of the environment with the genes and how it affects the growth and development of the body in general and dentofacial complex in particular. By utilizing twin studies, we can identify whether a particular trait, disease, or disorder is influenced more strongly by genetics or by the environment. Success of orthodontic treatment depends on a proper diagnosis of the problem including its etiological factors. Genetic studies let the orthodontists to understand the effects of genetic and environmental factors in the growth and development of dentofacial complex better and allows to prevent or treat malocclusions and skeletal anomalies in better ways.

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

PubMed Central

Adams, Dany Spencer; Uzel, Sebastien G. M.; Akagi, Jin; Wlodkowic, Donald; Andreeva, Viktoria; Yelick, Pamela Crotty; Devitt‐Lee, Adrian; Pare, Jean‐Francois; Levin, Michael

2016-01-01

Key points Xenopus laevis craniofacial development is a good system for the study of Andersen–Tawil Syndrome (ATS)‐associated craniofacial anomalies (CFAs) because (1) Kcnj2 is expressed in the nascent face; (2) molecular‐genetic and biophysical techniques are available for the study of ion‐dependent signalling during craniofacial morphogenesis; (3) as in humans, expression of variant Kcnj2 forms in embryos causes a muscle phenotype; and (4) variant forms of Kcnj2 found in human patients, when injected into frog embryos, cause CFAs in the same cell lineages.Forced expression of WT or variant Kcnj2 changes the normal pattern of V mem (resting potential) regionalization found in the ectoderm of neurulating embryos, and changes the normal pattern of expression of ten different genetic regulators of craniofacial development, including markers of cranial neural crest and of placodes.Expression of other potassium channels and two different light‐activated channels, all of which have an effect on V mem, causes CFAs like those induced by injection of Kcnj2 variants. In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an inactive Cl− channel, do not cause CFAs, demonstrating that correct craniofacial development depends on a pattern of bioelectric states, not on ion‐ or channel‐specific signalling.Using optogenetics to control both the location and the timing of ion flux in developing embryos, we show that affecting V mem of the ectoderm and no other cell layers is sufficient to cause CFAs, but only during early neurula stages. Changes in V mem induced late in neurulation do not affect craniofacial development.We interpret these data as strong evidence, consistent with our hypothesis, that ATS‐associated CFAs are caused by the effect of variant Kcnj2 on the V mem of ectodermal cells of the developing face. We predict that the critical time is early during neurulation, and the critical cells are the ectodermal cranial neural crest and placode lineages. This points to the potential utility of extant, ion flux‐modifying drugs as treatments to prevent CFAs associated with channelopathies such as ATS. Abstract Variants in potassium channel KCNJ2 cause Andersen–Tawil Syndrome (ATS); the induced craniofacial anomalies (CFAs) are entirely unexplained. We show that KCNJ2 is expressed in Xenopus and mouse during the earliest stages of craniofacial development. Misexpression in Xenopus of KCNJ2 carrying ATS‐associated mutations causes CFAs in the same structures affected in humans, changes the normal pattern of membrane voltage potential regionalization in the developing face and disrupts expression of important craniofacial patterning genes, revealing the endogenous control of craniofacial patterning by bioelectric cell states. By altering cells’ resting potentials using other ion translocators, we show that a change in ectodermal voltage, not tied to a specific protein or ion, is sufficient to cause CFAs. By adapting optogenetics for use in non‐neural cells in embryos, we show that developmentally patterned K+ flux is required for correct regionalization of the resting potentials and for establishment of endogenous early gene expression domains in the anterior ectoderm, and that variants in KCNJ2 disrupt this regionalization, leading to the CFAs seen in ATS patients. PMID:26864374

Craniofacial anomalies associated with hypospadias. Description of a hospital based population in South America.

PubMed

Fernandez, Nicolas; Escobar, Rebeca; Zarante, Ignacio

2016-01-01

Hypospadias is a congenital abnormality of the penis, in which there is incomplete development of the distal urethra. There are numerous reports showing na increase of prevalence of hypospadias. Association of craniofacial malformations in patients diagnosed with hypospadias is rare. The aim of this study is to describe the association between hypospadias and craniofacial congenital anomalies. A retrospective review of the Latin-American collaborative study of congenital malformations (ECLAMC) data was performed between January 1982 and December 2011. We included children diagnosed with associated hypospadias and among them we selected those that were associated with any craniofacial congenital anomaly. Global prevalence was 11.3 per 10.000 newborns. In this population a total of 809 patients with 1117 associated anomalies were identified. On average there were 1.7 anomalies per patient. Facial anomalies were present in 13.2%. The most commonly major facial anomaly associated to hypospadias was cleft lip/palate with 52 cases. We identified that 18% have an association with other anomalies, and found an association between craniofacial anomalies and hypospadias in 0.59 cases/10.000 newborns. Hypospadias is the most common congenital anomaly affecting the genitals. Its association with other anomalies is rare. It has been reported that other malformations occur in 29.3% of the cases with hypospadias. The more proximal the meatus, the higher the risk for having another associated anomaly. Associated hypospadias are rare, and it is important to identify the concurrent occurrence of craniofacial anomalies to better treat patients that might need a multidisciplinary approach. Copyright© by the International Brazilian Journal of Urology.

Craniofacial anomalies associated with hypospadias. Description of a hospital based population in South America

PubMed Central

Fernandez, Nicolas; Escobar, Rebeca; Zarante, Ignacio

2016-01-01

ABSTRACT Introduction: Hypospadias is a congenital abnormality of the penis, in which there is incomplete development of the distal urethra. There are numerous reports showing an increase of prevalence of hypospadias. Association of craniofacial malformations in patients diagnosed with hypospadias is rare. The aim of this study is to describe the association between hypospadias and craniofacial congenital anomalies. Materials and Methods: A retrospective review of the Latin-American collaborative study of congenital malformations (ECLAMC) data was performed between January 1982 and December 2011. We included children diagnosed with associated hypospadias and among them we selected those that were associated with any craniofacial congenital anomaly. Results: Global prevalence was 11.3 per 10.000 newborns. In this population a total of 809 patients with 1117 associated anomalies were identified. On average there were 1.7 anomalies per patient. Facial anomalies were present in 13.2%. The most commonly major facial anomaly associated to hypospadias was cleft lip/palate with 52 cases. We identified that 18% have an association with other anomalies, and found an association between craniofacial anomalies and hypospadias in 0.59 cases/10.000 newborns. Discussion: Hypospadias is the most common congenital anomaly affecting the genitals. Its association with other anomalies is rare. It has been reported that other malformations occur in 29.3% of the cases with hypospadias. The more proximal the meatus, the higher the risk for having another associated anomaly. Conclusion: Associated hypospadias are rare, and it is important to identify the concurrent occurrence of craniofacial anomalies to better treat patients that might need a multidisciplinary approach. PMID:27564292

Pediatric craniofacial fractures due to violence: comparing violent and nonviolent mechanisms of injury.

PubMed

Mericli, Alexander F; DeCesare, Gary E; Zuckerbraun, Noel S; Kurland, Kristen S; Grunwaldt, Lorelei; Vecchione, Lisa; Losee, Joseph E

2011-07-01

This study examines the epidemiologic data of pediatric craniofacial fractures secondary to violence, comparing these data to craniofacial fractures sustained from all other causes. A retrospective review was completed on all patients who presented to the emergency department of a major urban children's hospital from 2000 to 2005 with a craniofacial fracture. Data were compared between patients with fractures due to violent and nonviolent mechanisms. Socioeconomic analysis was performed using Geographic Information System mapping and 2000 US Census data by postal code. One thousand five hundred twenty-eight patients were diagnosed with skull and/or facial fractures. Isolated skull fractures were excluded, leaving 793 patients in the study. Ninety-eight children were injured due to violence, and 695 were injured from a nonviolent cause. Patients with violence-related fractures were more likely to be older, male, and nonwhite and live in a socioeconomically depressed area. A greater number of patients with violence-related injuries sustained nasal and mandible angle fractures, whereas more patients with non-violence-related injuries sustained skull and orbital fractures. Those with violence-related craniofacial fractures had a lower percentage of associated multiorgan system injuries and a lower rate of hospital admissions and intensive care unit admissions. The rate of open reduction and internal fixation for craniofacial fractures was similar in both groups. Patients with violence-related fractures had fewer associated serious injuries and lower morbidity and lived in a more socioeconomically depressed area. The information gained from this descriptive study improves our ability to characterize this population of pediatric patients and to identify the associated constellation of injuries in such fractures.

Psychological and Social Factors in Undergoing Reconstructive Surgery Among Individuals With Craniofacial Conditions: An Exploratory Study

PubMed Central

Bemmels, Heather; Biesecker, Barbara; Schmidt, Johanna L.; Krokosky, Alyson; Guidotti, Rick; Sutton, Erica J.

2012-01-01

Objective Reconstructive surgery to improve psychological well-being is commonly offered to children with craniofacial conditions. Few studies have explored the challenges of reconstructive surgery beyond the physical risks: poor treatment outcomes, infection, brain damage, and death. This qualitative study aims to understand the psychological and social implications such interventions can have for individuals with craniofacial conditions. Design A total of 38 individuals between the ages of 12 and 61 with such craniofacial conditions as Sturge-Weber syndrome, Treacher Collins syndrome, Möbius syndrome, cleft lip and palate, Noonan syndrome, Crouzon syndrome, and amniotic band syndrome participated in semistructured video-recorded interviews. Participants were recruited at conferences, through study flyers, and by word of mouth. Descriptive, thematic analysis was used to identify themes related to reconstructive surgery. Results Dominant themes included undergoing surgery to reduce stigmatization, the psychological and social implications of the interventions, outcome satisfaction, parental involvement in decision making about surgery, and recommendations for parents considering surgery for their children with craniofacial conditions. Experiences with reconstructive surgery varied, with some participants expressing surgical benefits and others, disillusionment. Conclusions The range of participant attitudes and experiences reflect the complexity of reconstructive surgery. Pediatric health care teams involved in the care of children with craniofacial conditions play an important role in advising patients (and their parents) about existing treatment options. The psychological and social implications of reconstructive surgery should be relayed to help families weigh the risks and benefits of surgery in an informed and meaningful way. PMID:22315960

Growth hormone positive effects on craniofacial complex in Turner syndrome.

PubMed

Juloski, Jovana; Dumančić, Jelena; Šćepan, Ivana; Lauc, Tomislav; Milašin, Jelena; Kaić, Zvonimir; Dumić, Miroslav; Babić, Marko

2016-11-01

Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. Copyright © 2016 Elsevier Ltd. All rights reserved.

Craniofacial duplication (diprosopus): report of a case with a review of the literature.

PubMed

Amr, S S; Hammouri, M F

1995-01-01

A case of craniofacial duplication (diprosopus) is presented. Details on this rare form of conjoined twins are described, and the proposed theories of its embryogenesis are discussed with brief review of the pertinent literature.

Surgical Treatment of Pediatric Craniofacial Fractures: A National Perspective.

PubMed

Massenburg, Benjamin B; Sanati-Mehrizy, Paymon; Taub, Peter J

2015-11-01

Head trauma is the most common cause of death because of injury in children, and trauma alone is the leading cause of morbidity and mortality in pediatrics. This study aimed to characterize the demographics and economic burden associated with the surgical and nonsurgical repair of craniofacial fractures in the pediatric inpatient population in the United States. A retrospective cohort study was performed using the 2012 Kids' Inpatient Database which identified 20,070 patients who had a skull or facial fracture, of whom 6395 (31.9%) were treated surgically. Epidemiologic patient and hospital data were analyzed as potential determinants of surgical treatment, prolonged hospitalizations, and higher charges. Pediatric craniofacial fractures are estimated to represent $1.2 billion of national healthcare expenditures annually. The average patient charge for surgical treatment of a craniofacial fracture in the pediatric population is $84,849 compared with $52,490 for nonsurgical management (P < 0.001), and the average length of stay was longer for surgical repair when compared with nonsurgical management for craniofacial fractures (5.3 days versus 4.6 days, P < 0.001). Patients who were older, African American, had nonprivate insurance, whose fracture was caused by external trauma, and who were treated in an urban hospital had an independently increased likelihood of surgical repair of craniofacial fractures. Patients who were older, female, insured, of lower income brackets, whose fracture was caused by a motor vehicle accident, who had surgical treatment of their craniofacial fracture, and who were treated in hospitals in the South, Midwest, or West, teaching hospitals, and government-owned hospitals had an independent risk for a prolonged hospitalization. Patients who were older, Caucasian, insured, whose fracture was caused by a motor vehicle accident, and who were treated in hospitals in the South, teaching hospitals, pediatric hospitals, larger hospitals, and government-owned hospitals had an independent risk for increased patient charges. Craniofacial fractures in the pediatric population represent a large economic burden to the patient and family, as well as the healthcare system as a whole. The identified patient and hospital demographics that are associated with prolonged hospital stays and higher patient charges may represent potential barriers to care, and additional research to elucidate these factors is warranted.

Amino Acid Sensing in Skeletal Muscle

PubMed Central

Moro, Tatiana; Ebert, Scott M.; Adams, Christopher M.; Rasmussen, Blake B.

2016-01-01

Aging impairs skeletal muscle protein synthesis, leading to muscle weakness and atrophy. However, the underlying molecular mechanisms remain poorly understood. Here, we review evidence that mTORC1- and ATF4-mediated amino acid sensing pathways, triggered by impaired amino acid delivery to aged skeletal muscle, may play important roles in skeletal muscle aging. Interventions that alleviate age-related impairments in muscle protein synthesis, strength and/or muscle mass appear to do so by reversing age-related changes in skeletal muscle amino acid delivery, mTORC1 activity and/or ATF4 activity. An improved understanding of the mechanisms and roles of amino acid sensing pathways in skeletal muscle may lead to evidence-based strategies to attenuate sarcopenia. PMID:27444066

Evaluation of the Transverse Craniofacial Morphology of Adolescents With Repaired Unilateral Cleft Lip and Palate Using Cone-Beam Computed Tomography.

PubMed

Buyuk, Suleyman Kutalmiş; Celikoglu, Mevlut; Benkli, Yasin Atakan; Sekerci, Ahmet Ercan

2016-10-01

The aim of the study was to evaluate the transverse craniofacial morphology of the adolescent patients affected by unilateral cleft lip and palate (UCLP) and to compare the findings with age- and sex-matched control group without any cleft using their cone-beam computed tomography (CBCT) images. The study sample (n = 56 patients; mean age: 14.35 ± 3.06 years) consisted of 26 UCLP (n = 26 patients; 10 women and 16 men; mean age: 13.70 ± 2.94 years) and 30 control (n = 30 patients; 19 women and 11 men; mean age: 14.90 ± 3.10 years) subjects. Twenty-five conventional skeletal and dental tissue landmarks were identified. Twenty widely used frontal cephalometric variables (14 linear distances, 3 angles, and 3 ratios) were measured. The data were analyzed using the independent t-test between the groups. Patients affected by UCLP had statistically significantly smaller interorbital width (89.83 ± 4.16 mm), maxillary width (58.02 ± 5.77 mm), maxillary intermolar width (52.83 ± 4.83 mm), and upper face height (57.64 ± 4.57 mm) (P < 0.05) compared with the control group. Conversely, ANS-isf distance was significantly greater in the UCLP group (29.62 ± 5.19 mm) than in the control group (26.74 ± 3.99 mm) (P = 0.023). Moreover, alveolar cleft width had significant effect on Cr-ANS (r = 0.446, P = 0.022) and the ANS-isf (r = 0.459, P = 0.018) measurements. The UCLP group showed statistically significantly smaller values for interorbital width, maxillary width, maxillary intermolar width, and upper face height than the noncleft controls.

Bone morphogenetic protein type I receptor inhibition induces cleft palate associated with micrognathia and cleft lower lip in mice.

PubMed

Lai, Yongzhen; Xie, Changfu; Zhang, Shixian; Gan, Guowu; Wu, Di; Chen, Weihui

2016-07-01

Gain-of- and loss-of-function studies have demonstrated that changes in bone morphogenetic protein (BMP) signaling during embryo development cause craniofacial malformations, including cleft palate. It remains uncertain whether BMP signaling could be targeted pharmacologically to affect craniofacial morphogenesis. Pregnant C57Bl/6J mice were treated with the BMP type I receptor inhibitor LDN-193189 at the dose of 3, 6, or 9 mg/kg twice a day by intraperitoneal injection from embryonic day 10.5 (E10.5) to E15.5. At E16.5, embryos were investigated by facial measurement analysis and histology to determine the optimal concentration for malformation. Subsequent embryonic phenotypes were analyzed in detail by histology, whole-mount skeletal staining, micro-computed tomography, and palatal organic culture. We further used immunohistochemistry to analyze protein expression of the BMP-mediated canonical and noncanonical signaling components. The optimal concentration of LDN-193189 was determined to be 6 mg/kg. In utero, LDN-193189 exposures induced partial clefting of the anterior palate or complete cleft palate, which was attributed to a reduced cell proliferation rate in the secondary palate, and delayed palatal elevation caused by micrognathia. Analysis of signal transduction in palatal shelves at E12.5 and E13.5 identified a significant reduction of BMP/Smad signaling (p-Smad1/5/8) and unchanged BMP noncanonical signaling (p-p38, p-Erk1/2) after treatment with LDN-193189. The results of this study indicate that LDN-193189 can be used to manipulate BMP signaling by selectively targeting the BMP/Smad signaling pathway to affect palatal morphogenesis and produce phenotypes mimicking those caused by genetic mutations. This work established a novel mouse model for teratogen-induced cleft palate. Birth Defects Research (Part A) 106:612-623, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Critical Role of TRPM7 As an Ion Channel Protein in Mediating the Mineralization of the Craniofacial Hard Tissues

PubMed Central

Nakano, Yukiko; Le, Michael H.; Abduweli, Dawud; Ho, Sunita P.; Ryazanova, Lillia V.; Hu, Zhixian; Ryazanov, Alexey G.; Den Besten, Pamela K.; Zhang, Yan

2016-01-01

Magnesium ion (Mg2+) is the fourth most common cation in the human body, and has a crucial role in many physiological functions. Mg2+ homeostasis is an important contributor to bone development, however, its roles in the development of dental mineralized tissues have not yet been well known. We identified that transient receptor potential cation channel, subfamily M, member 7 (TRPM7), was significantly upregulated in the mature ameloblasts as compared to other ameloblasts through our whole transcript microarray analyses of the ameloblasts. TRPM7, an ion channel for divalent metal cations with an intrinsic serine/threonine protein kinase activity, has been characterized as a key regulator of whole body Mg2+ homeostasis. Semi-quantitative PCR and immunostaining for TRMP7 confirmed its upregulation during the maturation stage of enamel formation, at which ameloblasts direct rapid mineralization of the enamel matrix. The significantly hypomineralized craniofacial structures, including incisors, molars, and cranial bones were demonstrated by microCT analysis, von Kossa and trichrome staining in Trpm7Δkinase∕+ mice. A previously generated heterozygous mouse model with the deletion of the TRPM7 kinase domain. Interestingly, the skeletal phenotype of Trpm7Δkinase∕+ mice resembled those found in the tissue-nonspecific alkaline phosphatase (Alpl) KO mice, thus we further examined whether ALPL protein content and alkaline phosphatase (ALPase) activity in ameloblasts, odontoblasts and osteoblasts were affected in those mice. While ALPL protein in Trpm7Δkinase∕+ mice remained at the similar level as that in wt mice, ALPase activities in the Trpm7Δkinase∕+ mice were almost nonexistent. Supplemented magnesium successfully rescued the activities of ALPase in ameloblasts, odontoblasts and osteoblasts of Trpm7Δkinase∕+ mice. These results suggested that TRPM7 is essential for mineralization of enamel as well as dentin and bone by providing sufficient Mg2+ for the ALPL activity, underlining the key importance of ALPL for biomineralization. PMID:27458382

EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

EPA Science Inventory

Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

76 FR 58284 - National Institute of Dental and Craniofacial Research; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... Craniofacial Research Special Emphasis Panel; Teleconference Review of Pre Clinical (R34) and Secondary Data Analysis (R03) Applications. Dates: October 18, 2011. Time: 11 a.m. to 1 p.m. Agenda: To review and...

pitx2 Deficiency Results in Abnormal Ocular and Craniofacial Development in Zebrafish

PubMed Central

Liu, Yi; Semina, Elena V.

2012-01-01

Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6–8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates. PMID:22303467

Embryonic fate map of first pharyngeal arch structures in the sox10: kaede zebrafish transgenic model.

PubMed

Dougherty, Max; Kamel, George; Shubinets, Valeriy; Hickey, Graham; Grimaldi, Michael; Liao, Eric C

2012-09-01

Cranial neural crest cells follow stereotypic patterns of migration to form craniofacial structures. The zebrafish is a powerful vertebrate genetic model where transgenics with reporter proteins under the transcriptional regulation of lineage-specific promoters can be generated. Numerous studies demonstrate that the zebrafish ethmoid plate is embryologically analogous to the mammalian palate. A fate map correlating embryonic cranial neural crest to defined jaw structures would provide a useful context for the morphogenetic analysis of craniofacial development. To that end, the sox10:kaede transgenic was generated, where sox10 provides lineage restriction to the neural crest. Specific regions of neural crest were labeled at the 10-somite stage by photoconversion of the kaede reporter protein. Lineage analysis was carried out during pharyngeal development in wild-type animals, after miR140 injection, and after estradiol treatment. At the 10-somite stage, cranial neural crest cells anterior of the eye contributed to the median ethmoid plate, whereas cells medial to the eye formed the lateral ethmoid plate and trabeculae and a posterior population formed the mandible. miR-140 overexpression and estradiol inhibition of Hedgehog signaling resulted in cleft development, with failed migration of the anterior cell population to form the median ethmoid plate. The sox10:kaede transgenic line provides a useful tool for neural crest lineage analysis. These studies illustrate the advantages of the zebrafish model for application in morphogenetic studies of vertebrate craniofacial development.

Craniofacial Reconstruction Using Rational Cubic Ball Curves

PubMed Central

Majeed, Abdul; Mt Piah, Abd Rahni; Gobithaasan, R. U.; Yahya, Zainor Ridzuan

2015-01-01

This paper proposes the reconstruction of craniofacial fracture using rational cubic Ball curve. The idea of choosing Ball curve is based on its robustness of computing efficiency over Bezier curve. The main steps are conversion of Digital Imaging and Communications in Medicine (Dicom) images to binary images, boundary extraction and corner point detection, Ball curve fitting with genetic algorithm and final solution conversion to Dicom format. The last section illustrates a real case of craniofacial reconstruction using the proposed method which clearly indicates the applicability of this method. A Graphical User Interface (GUI) has also been developed for practical application. PMID:25880632

A personal tribute to a great educator: how Henry Kawamoto influenced my interest in facial soft tissue anatomy and changed my plastic surgery career.

PubMed

Stuzin, James M

2012-11-01

Henry Kawamoto remains one of the most influential craniofacial surgeons of the 20th century. A Tessier-trained craniofacial surgeon, Dr. Kawamoto has personally influenced not only the lives of his patients, but significantly also the lives of those craniofacial fellows he educated, passing on the Tessier methodology to future generations. This article serves as an anecdote as to how Dr. Kawamoto's mentoring influenced a personal understanding of facial soft tissue anatomy, leading to improved technical approaches for surgical rejuvenation of the aging face.

Connective tissue cells expressing fibro/adipogenic progenitor markers increase under chronic damage: relevance in fibroblast-myofibroblast differentiation and skeletal muscle fibrosis.

PubMed

Contreras, Osvaldo; Rebolledo, Daniela L; Oyarzún, Juan Esteban; Olguín, Hugo C; Brandan, Enrique

2016-06-01

Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition.

Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

PubMed

Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

2017-09-01

The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

Normalized Shape and Location of Perturbed Craniofacial Structures in the Xenopus Tadpole Reveal an Innate Ability to Achieve Correct Morphology

PubMed Central

Vandenberg, Laura N.; Adams, Dany S.; Levin, Michael

2012-01-01

Background Embryonic development can often adjust its morphogenetic processes to counteract external perturbation. The existence of self-monitoring responses during pattern formation is of considerable importance to the biomedicine of birth defects, but has not been quantitatively addressed. To understand the computational capabilities of biological tissues in a molecularly-tractable model system, we induced craniofacial defects in Xenopus embryos, then tracked tadpoles with craniofacial deformities and used geometric morphometric techniques to characterize changes in the shape and position of the craniofacial structures. Results Canonical variate analysis revealed that the shapes and relative positions of perturbed jaws and branchial arches were corrected during the first few months of tadpole development. Analysis of the relative movements of the anterior-most structures indicates that misplaced structures move along the anterior-posterior and left-right axes in ways that are significantly different from their normal movements. Conclusions Our data suggest a model in which craniofacial structures utilize a measuring mechanism to assess and adjust their location relative to other local organs. Understanding the correction mechanisms at work in this system could lead to the better understanding of the adaptive decision-making capabilities of living tissues and suggest new approaches to correct birth defects in humans. PMID:22411736

Bilateral lambdoid and sagittal synostosis (BLSS): a unique craniosynostosis syndrome or predictable craniofacial phenotype?

PubMed

Hing, Anne V; Click, Eleanor S; Holder, Ursula; Seto, Marianne L; Vessey, Kyle; Gruss, Joseph; Hopper, Richard; Cunningham, Michael L

2009-05-01

Multisutural craniosynostosis that includes bilateral lambdoid and sagittal synostosis (BLSS) results in a very characteristic head shape with frontal bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and inferior displacement of the ears. This entity has been reported both in the genetics literature as craniofacial dyssynostosis and in the surgical literature as "Mercedes Benz" syndrome. Craniofacial dyssynostosis was first described in 1976 by Dr. Neuhauser when he presented a series of seven patients with synostosis of the sagittal and lambdoid sutures, short stature, and developmental delay. Over the past 30 years nine additional patients with craniofacial dyssynostosis have been reported in the literature adding to the growing evidence for a distinct craniosynostosis syndrome. The term "Mercedes Benz" syndrome was coined by Moore et al. in 1998 due to the characteristic appearance of the fused sutures on three-dimensional CT imaging. In contrast to the aforementioned reported cases of craniofacial dyssynostosis, all three patients had normal development. Recently, there have been several case reports of patients with BLSS and distinct chromosomal anomalies. These findings suggest that BLSS is a heterogeneous disorder perhaps with syndromic, chromosomal, and isolated forms. In this manuscript we will present the largest series of patients with BLSS and review clinical, CT, and molecular findings.

Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

PubMed

Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

2007-07-01

To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

How Useful Are Skeletal Surveys in the Second Year of Life?

ERIC Educational Resources Information Center

Hansen, Karen Kirhofer; Campbell, Kristine A.

2009-01-01

Objective: To evaluate the utility of skeletal surveys in cases of possible physical abuse in the second year of life. Methods: Radiology records for all children under 24 months of age referred to our child protection team from January 2002 through November 2006, who had a skeletal survey performed and/or interpreted by the pediatric radiologists…

mRNA-seq reveals skeletal muscle atrophy in response to handling stress in a marine teleost, the red cusk-eel (Genypterus chilensis).

PubMed

Aedo, Jorge E; Maldonado, Jonathan; Aballai, Víctor; Estrada, Juan M; Bastias-Molina, Macarena; Meneses, Claudio; Gallardo-Escarate, Cristian; Silva, Herman; Molina, Alfredo; Valdés, Juan A

2015-12-01

Fish reared under intensive conditions are repeatedly exposed to stress, which negatively impacts growth. Although most fish follow a conserved pattern of stress response, with increased concentrations of cortisol, each species presents specificities in the cell response and stress tolerance. Therefore, culturing new species requires a detailed knowledge of these specific responses. The red cusk-eel (Genypterus chilensis) is a new economically important marine species for the Chilean aquaculture industry. However, there is no information on the stress- and cortisol-induced mechanisms that decrease skeletal muscle growth in this teleost. Using Illumina RNA-seq technology, skeletal muscle sequence reads for G. chilensis were generated under control and handling stress conditions. Reads were mapped onto a reference transcriptome, resulting in the in silico identification of 785 up-regulated and 167 down-regulated transcripts. Gene ontology enrichment analysis revealed a significant up-regulation of catabolic genes associated with skeletal muscle atrophy. These results were validated by RT-qPCR analysis for ten candidates genes involved in ubiquitin-mediated proteolysis, autophagy and skeletal muscle growth. Additionally, using a primary culture of fish skeletal muscle cells, the effect of cortisol was evaluated in relation to red cusk-eel skeletal muscle atrophy. The present data demonstrated that handling stress promotes skeletal muscle atrophy in the marine teleost G. chilensis through the expression of components of the ubiquitin-proteasome and autophagy-lysosome systems. Furthermore, cortisol was a powerful inductor of skeletal muscle atrophy in fish myotubes. This study is an important step towards understanding the atrophy system in non-model teleost species and provides novel insights on the cellular and molecular mechanisms that control skeletal muscle growth in early vertebrates.

Comparing phototoxicity during the development of a zebrafish craniofacial bone using confocal and light sheet fluorescence microscopy techniques.

PubMed

Jemielita, Matthew; Taormina, Michael J; Delaurier, April; Kimmel, Charles B; Parthasarathy, Raghuveer

2013-12-01

The combination of genetically encoded fluorescent proteins and three-dimensional imaging enables cell-type-specific studies of embryogenesis. Light sheet microscopy, in which fluorescence excitation is provided by a plane of laser light, is an appealing approach to live imaging due to its high speed and efficient use of photons. While the advantages of rapid imaging are apparent from recent work, the importance of low light levels to studies of development is not well established. We examine the zebrafish opercle, a craniofacial bone that exhibits pronounced shape changes at early developmental stages, using both spinning disk confocal and light sheet microscopies of fluorescent osteoblast cells. We find normal and aberrant opercle morphologies for specimens imaged with short time intervals using light sheet and spinning disk confocal microscopies, respectively, under equivalent exposure conditions over developmentally-relevant time scales. Quantification of shapes reveals that the differently imaged specimens travel along distinct trajectories in morphological space. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

75 FR 58409 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and Craniofacial... Kelly, Scientific Review Officer, Scientific Review Branch, [[Page 58410

Reflections on my journey in biomedical research: the art, science, and politics of advocacy.

PubMed

Slavkin, H C

2013-01-01

Scientific Discovery often reflects the art, science, and advocacy for biomedical research. Here the author reflects on selected highlights of discovery that contributed to several aspects of our understanding of craniofacial biology and craniofacial diseases and disorders.

PATHOGENESIS OF METHANOL-INDUCED CRANIOFACIAL DEFECTS IN C57BL/6J MICE

EPA Science Inventory

BACKGROUND: Methanol administered to C57BL/6J mice during gastrulation causes severe craniofacial dysmorphology. We describe dysmorphogenesis, cell death, cell cycle assessment, and effects on development of cranial ganglia and nerves observed following administration of methanol...

Maternal diet supplementation with methyl donors and increased parity affect the incidence of craniofacial defects in the offspring of twisted gastrulation mutant mice.

PubMed

Billington, Charles J; Schmidt, Brian; Zhang, Lei; Hodges, James S; Georgieff, Michael K; Schotta, Gunnar; Gopalakrishnan, Rajaram; Petryk, Anna

2013-03-01

Diets rich in methyl-donating compounds, including folate, can provide protection against neural tube defects, but their role in preventing craniofacial defects is less clear. Mice deficient in Twisted gastrulation (TWSG1), an extracellular modulator of bone morphogenetic protein signaling, manifest both midline facial defects and jaw defects, allowing study of the effects of methyl donors on various craniofacial defects in an experimentally tractable animal model. The goal of this study was to examine the effects of maternal dietary supplementation with methyl donors on the incidence and type of craniofacial defects among Twsg1(-/-) offspring. Nulliparous and primiparous female mice were fed an NIH31 standard diet (control) or a methyl donor supplemented (MDS) diet (folate, vitamin B-12, betaine, and choline). Observed defects in the pups were divided into those derived mostly from the first branchial arch (BA1) (micrognathia, agnathia, cleft palate) and midline facial defects in the holoprosencephaly spectrum (cyclopia, proboscis, and anterior truncation). In the first pregnancy, offspring of mice fed the MDS diet had lower incidence of BA1-derived defects (12.8% in MDS vs. 32.5% in control; P = 0.02) but similar incidence of midline facial defects (6.4% in MDS vs. 5.2% in control; P = 1.0). Increased maternal parity was independently associated with increased incidence of craniofacial defects after adjusting for diet (from 37.7 to 59.5% in control, P = 0.04 and from 19.1 to 45.3% in MDS, P = 0.045). In conclusion, methyl donor supplementation shows protective effects against jaw defects, but not midline facial defects, and increased parity can be a risk factor for some craniofacial defects.

Children of the Philippines: attitudes toward visible physical impairment.

PubMed

Harper, D C; Peterson, D B

2001-11-01

This pilot study was designed to evaluate children's attitudes and understanding of physical disabilities with special reference to those with craniofacial anomalies in the Philippines. Children with and without craniofacial anomalies were studied. This was a two-group correlational design with additional statistical assessment of subgroup differences. Each group was interviewed and information obtained on a standard disability preference task, attributions for playmate choice, and frequency of contact with disabilities. Parents completed a structured interview. Participants were 122 children recruited from Negros, Philippines. Fifty-four children with craniofacial anomalies (aged 7 to 12 years) were enrolled in the study, and 68 children without any disabilities were recruited from a local school in Bacolod City, Negros, Philippines. Participants completed a picture-ranking interview of specific physical disabilities and provided their reasons for their play choices and their contact with physical disabilities. The Kendall W correlation was significant for the children with craniofacial anomalies and for those without physical disabilities. Both groups reported lower preferences for disabilities that interfere with play and social interactions. Children depicted with facial anomalies received lower preference, compared with other physical disabilities. Children with craniofacial anomalies who have experienced surgical repair reported more positive rankings for the child depicted with a facial cleft. Sex differences in disability preference were noted. Children in the Philippines with and without craniofacial differences revealed similarities in preferences to children in several Western (United States) and non-Western countries. Children depicted with facial anomalies received lower preference than other visible physical differences. Children reported both positive and negative explanations for their disability play preferences. Facial differences may result in illogical and negative explanations for social avoidance among children. Similar reactions are noted in other parts of the world.

Craniofacial resection for nonmelanoma skin cancer of the head and neck.

PubMed

Backous, Douglas D; DeMonte, Franco; El-Naggar, Adel; Wolf, Pat; Weber, Randal S

2005-06-01

We reviewed our experience with craniofacial resection for advanced, nonmelanoma skin cancer of the head and neck to determine prognostic factors, local control rate, disease free survival, morbidity, and mortality. Retrospective review of consecutive patients treated at a tertiary referral center from 1982 to 1993. Charts of patients having craniofacial resection for aggressive nonmelanoma cutaneous malignancies were reviewed and living patients followed for 10 additional years. Demographics, histology, previous interventions, treatment, surgical pathology, reconstructions, and complications were examined. The product-limit method was used to calculate survival functions, and the log-rank test was used to compare survival distributions. Thirty-five patients, mean age 66.7 years, received treatment at our facility. Follow-up ranged from 2 to 191 (mean 47.4) months. Histology included 20 squamous cell carcinomas (SCC) and 15 basal cell carcinomas (BCC). Sixty percent had craniofacial resection alone, and 28.6% also had postoperative radiotherapy. There were two perioperative deaths, and 37.1% suffered early and 14.3% late surgical complications. Two- and five- year survival was significantly better (P=.02) with BCC (92% and 76%) than with SCC (54% and 24%). Long-term disease-specific survival was 20%, and 11.4% of our subjects were living with disease. Intracranial extension (P=.02), perineural invasion (P=.049), and prior radiotherapy significantly decreased 5-year survival. Acceptable mortality and morbidity is possible using craniofacial resection to treat advanced nonmelanoma skin cancer. Although disease-specific survival remains poor, positive trends were noted in local control beginning at 2 years of follow-up. Because patients often have few remaining options for cure, craniofacial resection is justified when technically feasible.

An Anthropometric Study of Cranio-Facial Measurements and Their Correlation with Vertical Dimension of Occlusion among Saudi Arabian Subpopulations.

PubMed

Majeed, Muhammed Irfan; Haralur, Satheesh B; Khan, Muhammed Farhan; Al Ahmari, Maram Awdah; Al Shahrani, Nourah Falah; Shaik, Sharaz

2018-04-15

Determining and restoring physiological vertical dimension of occlusion (VDO) is the critical step during complete mouth rehabilitation. The improper VDO compromises the aesthetics, phonetics and functional efficiency of the prosthesis. Various methods are suggested to determine the accurate VDO, including the facial measurements in the clinical situations with no pre-extraction records. The generalisation of correlation between the facial measurements to VDO is criticised due to gender dimorphism and racial differences. Hence, it is prudent to verify the hypothesis of facial proportion and correlation of lower third of the face to remaining craniofacial measurements in different ethnic groups. The objective of the study was to evaluate the correlation of craniofacial measurements and OVD in the Saudi-Arabian ethnic group. Total of 228 participants from Saudi-Arabian Ethnic group were randomly recruited in this cross-sectional study. Fifteen craniofacial measurements were recorded with modified digital Vernier callipers, and OVD was recorded at centric occlusion. The obtained data were analysed by using the Spearman's correlation and linear regression analysis. The Mean OVD in male participants was higher (69.25 ± 5.54) in comparison to female participants (57.41 ± 5.32). The craniofacial measurement of Exocanthion-right labial commissure and the Mesial wall of the right external auditory canal-orbitale lateral had a strong positive correlation with VDO. The strong correlation was recorded with a trichion-upper border of right eyebrow line and trichion-Nasion only in males. Meanwhile, the length of an auricle recorded the positive correlation in female participants. Being simple and non-invasive technique, craniofacial measurements and linear equations could be routinely utilised to determine VDO.

Academic Productivity of Faculty Associated With Craniofacial Surgery Fellowship Programs.

PubMed

Ruan, Qing Zhao; Ricci, Joseph A; Silvestre, Jason; Ho, Olivia A; Ganor, Oren; Lee, Bernard T

2017-11-01

The H-index is increasingly being used as a measure of academic productivity and has been applied to various surgical disciplines. Here the authors calculate the H-index of craniofacial surgery fellowship faculty in North America in order to determine its utility for academic productivity among craniofacial surgeons. A list of fellowship programs was obtained from the website of the American Society of Craniofacial Surgery. Faculty demographics and institution characteristics were obtained from official program websites and the H-index was calculated using Scopus (Elsevier, USA). Data were assessed using bivariate analysis tools (Kruskal-Wallis and Mann-Whitney tests) to determine the relationship between independent variables and career publications, H-index and 5-year H-index (H5-index) of faculty. Dunn test for multiple comparisons was also calculated. A total of 102 faculty members from 29 craniofacial surgery fellowship programs were identified and included. Faculty demographics reflected a median age of 48 (interquartile range [IQR] 13), a predominantly male sample (88/102, 89.7%), and the rank of assistant professor being the most common among faculty members (41/102, 40.2%). Median of career publications per faculty was 37 (IQR 52.5) and medians of H-index and H5-index were 10.0 (IQR 13.75) and 3.5 (IQR 3.25), respectively. Greater age, male gender, Fellow of the American College of Surgeons membership, higher academic rank, and program affiliation with ranked research medical schools were significantly associated with higher H-indices. Variables associated with seniority were positively associated with the H-index. These results suggest that the H-index may be used as an adjunct in determining academic productivity for promotions among craniofacial surgeons.

The mitochondrial phylogeny of an ancient lineage of ray-finned fishes (Polypteridae) with implications for the evolution of body elongation, pelvic fin loss, and craniofacial morphology in Osteichthyes

PubMed Central

2010-01-01

Background The family Polypteridae, commonly known as "bichirs", is a lineage that diverged early in the evolutionary history of Actinopterygii (ray-finned fish), but has been the subject of far less evolutionary study than other members of that clade. Uncovering patterns of morphological change within Polypteridae provides an important opportunity to evaluate if the mechanisms underlying morphological evolution are shared among actinoptyerygians, and in fact, perhaps the entire osteichthyan (bony fish and tetrapods) tree of life. However, the greatest impediment to elucidating these patterns is the lack of a well-resolved, highly-supported phylogenetic tree of Polypteridae. In fact, the interrelationships of polypterid species have never been subject to molecular phylogenetic analysis. Here, we infer the first molecular phylogeny of bichirs, including all 12 recognized species and multiple subspecies using Bayesian analyses of 16S and cyt-b mtDNA. We use this mitochondrial phylogeny, ancestral state reconstruction, and geometric morphometrics to test whether patterns of morphological evolution, including the evolution of body elongation, pelvic fin reduction, and craniofacial morphology, are shared throughout the osteichthyan tree of life. Results Our molecular phylogeny reveals 1) a basal divergence between Erpetoichthys and Polypterus, 2) polyphyly of P. endlicheri and P. palmas, and thus 3) the current taxonomy of Polypteridae masks its underlying genetic diversity. Ancestral state reconstructions suggest that pelvic fins were lost independently in Erpetoichthys, and unambiguously estimate multiple independent derivations of body elongation and shortening. Our mitochondrial phylogeny suggested species that have lower jaw protrusion and up-righted orbit are closely related to each other, indicating a single transformation of craniofacial morphology. Conclusion The mitochondrial phylogeny of polypterid fish provides a strongly-supported phylogenetic framework for future comparative evolutionary, physiological, ecological, and genetic analyses. Indeed, ancestral reconstruction and geometric morphometric analyses revealed that the patterns of morphological evolution in Polypteridae are similar to those seen in other osteichthyans, thus implying the underlying genetic and developmental mechanisms responsible for those patterns were established early in the evolutionary history of Osteichthyes. We propose developmental and genetic mechanisms to be tested under the light of this new phylogenetic framework. PMID:20100320

Three-dimensional Imaging Methods for Quantitative Analysis of Facial Soft Tissues and Skeletal Morphology in Patients with Orofacial Clefts: A Systematic Review

PubMed Central

Kuijpers, Mette A. R.; Chiu, Yu-Ting; Nada, Rania M.; Carels, Carine E. L.; Fudalej, Piotr S.

2014-01-01

Background Current guidelines for evaluating cleft palate treatments are mostly based on two-dimensional (2D) evaluation, but three-dimensional (3D) imaging methods to assess treatment outcome are steadily rising. Objective To identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate. Data sources Literature was searched using PubMed (1948–2012), EMBASE (1980–2012), Scopus (2004–2012), Web of Science (1945–2012), and the Cochrane Library. The last search was performed September 30, 2012. Reference lists were hand searched for potentially eligible studies. There was no language restriction. Study selection We included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample size had at least one cleft type. Only primary publications were included. Data extraction Independent extraction of data and quality assessments were performed by two observers. Results Five hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements; therefore, only a systematic review could be conducted. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time. Conclusion Available evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate it. Systematic review registration International Prospective Register of Systematic Reviews, PROSPERO CRD42012002041 PMID:24710215

77 FR 59202 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and... Review Officer, Scientific Review Branch, National Institute of Dental & Craniofacial Research, National...

Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

PubMed

Arce-Estrada, Gabriel Emmanuel; Gómez-Toscano, Valeria; Cedillo-Peláez, Carlos; Sesman-Bernal, Ana Luisa; Bosch-Canto, Vanessa; Mayorga-Butrón, José Luis; Vargas-Villavicencio, José Antonio; Correa, Dolores

2017-07-03

We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. A two-month-old male had a twin in utero who disappeared between the 7 th and the 14 th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Advances in imaging: impact on studying craniofacial bone structure.

PubMed

Majumdar, S

2003-01-01

Methods for measuring the structure of craniofacial bones are discussed in this paper. In addition to the three-dimensional macro-structure of the craniofacial skeleton, there is considerable interest in imaging the bone at a microscopic resolution in order to depict the micro-architecture of the trabecular bone itself. In addition to the density of the bone, the microarchitecture reflects bone quality. An understanding of bone quality and density changes has implications for a number of craniofacial pathologies, as well as for implant design and understanding the biomechanical function and loading of the jaw. Trabecular bone micro-architecture has been recently imaged using imaging methods such as micro-computed tomography, magnetic resonance imaging, and the images have been used in finite element models to assess bone mechanical properties. In this paper, some of the recent advances in micro-computed tomography and magnetic resonance imaging are reviewed, and their potential for imaging the trabecular bone in mandibular bones is presented. Examples of in vitro and in vivo images are presented.

Craniofacial morphometric analysis of mandibular prognathism.

PubMed

Chang, H P; Liu, P H; Yang, Y H; Lin, H C; Chang, C H

2006-03-01

The purpose of this study was to provide more information about the morphological characteristics of the craniofacial complex in mandibular prognathism. Forty young adult males having mandibular prognathism were compared with 40 having normal occlusion. This was conducted to carry out geometric morphometric assessments to localize alterations, using Procrustes analysis and thin-plate spline analysis, in addition to conventional cephalometric techniques. Procrustes analysis indicated that the mean craniofacial, midfacial and mandibular morphology was significantly different in prognathic subjects compared with normal controls. This finding was corroborated by the multivariate Hotelling T(2)-test of cephalometric variables. Mandibular prognathism demonstrated a shorter and slightly retropositioned maxilla, a greater total length and anterior positioning of the mandible. Thin-plate spline analysis revealed a developmental diminution of the palatomaxillary region anteroposteriorly and a developmental elongation of the mandible anteroposteriorly, leading to the appearance of a prognathic mandibular profile. In conclusion, thin-plate spline analysis seems to provide a valuable supplement for conventional cephalometric analysis because the complex patterns of craniofacial shape change are visualized suggestive by means of grid deformations.

SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling.

PubMed

Vasudevan, Harish N; Soriano, Philippe

2014-11-10

Receptor tyrosine kinase signaling is critical for mammalian craniofacial development, but the key downstream transcriptional effectors remain unknown. We demonstrate that serum response factor (SRF) is induced by both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling in mouse embryonic palatal mesenchyme cells and that Srf neural crest conditional mutants exhibit facial clefting accompanied by proliferation and migration defects. Srf and Pdgfra mutants interact genetically in craniofacial development, but Srf and Fgfr1 mutants do not. This signal specificity is recapitulated at the level of cofactor activation: while both PDGF and FGF target gene promoters show enriched genome-wide overlap with SRF ChIP-seq peaks, PDGF selectively activates a network of MRTF-dependent cytoskeletal genes. Collectively, our results identify a role for SRF in proliferation and migration during craniofacial development and delineate a mechanism of receptor tyrosine kinase specificity mediated through differential cofactor usage, leading to a PDGF-responsive SRF-driven transcriptional program in the midface. Copyright © 2014 Elsevier Inc. All rights reserved.

Surgical Management of Polyostotic Craniofacial Fibrous Dysplasia: Long-Term Outcomes and Predictors for Postoperative Regrowth

PubMed Central

Boyce, Alison M.; Burke, Andrea; Peck, Carolee Cutler; DuFresne, Craig R.; Lee, Janice S.; Collins, Michael T.

2017-01-01

Background The mainstay of treatment for craniofacial fibrous dysplasia is surgical; however, optimal indications and techniques are poorly understood, particularly in polyostotic disease and McCune-Albright syndrome. This study investigated surgical indications and risk factors for recurrence in a large cohort. Methods One hundred thirty-three craniofacial fibrous dysplasia subjects in a natural history study were evaluated. Radiographic studies, operative reports, and clinical records were reviewed. Results Thirty-six subjects underwent 103 craniofacial procedures (mean, 2.8 operations per subject), with 13.5 ± 10.5-year follow-up (range, 0 to 39 years). The most common indication was craniofacial deformity (n = 61 operations), including 36 initial operations (59 percent) and 26 reoperations (41 percent). Mean time to reoperation was 3.4 ± 3.2 years (range, 0.3 to 13.3 years). Re-growth occurred after 42 operations (68 percent), and was more frequent after operations in subjects with McCune-Albright syndrome growth hormone excess [22 of 25 operations (88 percent)] than without growth hormone excess [15 of 36 operations (58 percent); p = 0.02]. Of 11 subjects with growth hormone excess, nine (82 percent) were undiagnosed at the time of their initial operation. Regrowth was more frequent after debulking procedures [31 of 38 (82 percent)] than after more aggressive reconstructions [nine of 20 (45 percent); p = 0.007]. Eleven subjects underwent treatment for aneurysmal bone cysts, with recurrence in one subject. Eleven subjects underwent biopsies and none had complications or regrowth. Conclusions Craniofacial fibrous dysplasia regrowth and reoperation are common, particularly after debulking procedures. Outcomes are favorable for aneurysmal bone cysts and biopsies. McCune-Albright syndrome growth hormone excess is a risk factor for regrowth, and may be underdiagnosed in surgical patients. Surgeons should be aware of appropriate screening for endocrinopathies in fibrous dysplasia. These findings highlight the importance of a multidisciplinary approach to craniofacial fibrous dysplasia, and individualized care with long-term follow-up. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV. PMID:27219238

A PCA-Based method for determining craniofacial relationship and sexual dimorphism of facial shapes.

PubMed

Shui, Wuyang; Zhou, Mingquan; Maddock, Steve; He, Taiping; Wang, Xingce; Deng, Qingqiong

2017-11-01

Previous studies have used principal component analysis (PCA) to investigate the craniofacial relationship, as well as sex determination using facial factors. However, few studies have investigated the extent to which the choice of principal components (PCs) affects the analysis of craniofacial relationship and sexual dimorphism. In this paper, we propose a PCA-based method for visual and quantitative analysis, using 140 samples of 3D heads (70 male and 70 female), produced from computed tomography (CT) images. There are two parts to the method. First, skull and facial landmarks are manually marked to guide the model's registration so that dense corresponding vertices occupy the same relative position in every sample. Statistical shape spaces of the skull and face in dense corresponding vertices are constructed using PCA. Variations in these vertices, captured in every principal component (PC), are visualized to observe shape variability. The correlations of skull- and face-based PC scores are analysed, and linear regression is used to fit the craniofacial relationship. We compute the PC coefficients of a face based on this craniofacial relationship and the PC scores of a skull, and apply the coefficients to estimate a 3D face for the skull. To evaluate the accuracy of the computed craniofacial relationship, the mean and standard deviation of every vertex between the two models are computed, where these models are reconstructed using real PC scores and coefficients. Second, each PC in facial space is analysed for sex determination, for which support vector machines (SVMs) are used. We examined the correlation between PCs and sex, and explored the extent to which the choice of PCs affects the expression of sexual dimorphism. Our results suggest that skull- and face-based PCs can be used to describe the craniofacial relationship and that the accuracy of the method can be improved by using an increased number of face-based PCs. The results show that the accuracy of the sex classification is related to the choice of PCs. The highest sex classification rate is 91.43% using our method. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhanced Skeletal Muscle Expression of EcSOD Mitigates Streptozotocin-Induced Diabetic Cardiomyopathy by Reducing Oxidative Stress and Aberrant Cell Signaling

PubMed Central

Call, Jarrod A.; Chain, Kristopher H.; Martin, Kyle S.; Lira, Vitor A.; Okutsu, Mitsuharu; Zhang, Mei; Yan, Zhen

2015-01-01

Background Exercise training enhances extracellular superoxide dismutase (EcSOD) expression in skeletal muscle and elicits positive health outcomes in individuals with diabetes. The goal of this study was to determine if enhanced skeletal muscle expression of EcSOD is sufficient to mitigate streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM). Methods and Results Exercise training promotes EcSOD expression in skeletal muscle and provides protection against DCM; however, it is not known if enhanced EcSOD expression in skeletal muscle plays a functional role in this protection. Here, we show that skeletal muscle-specific EcSOD transgenic mice (TG) are protected from cardiac hypertrophy, fibrosis and dysfunction under the condition of type-1 diabetes induced by STZ injection. We also show that both exercise training and muscle-specific transgenic expression of EcSOD result in elevated EcSOD protein in the blood and heart without increased transcription in the heart, suggesting enhanced expression of EcSOD from skeletal muscle redistributes to the heart. Importantly, cardiac tissue in TG mice displayed significantly reduced oxidative stress, aberrant cell signaling and inflammatory cytokine expression compared with wild type mice under the same diabetic condition. Conclusions Enhanced expression of EcSOD in skeletal muscle is sufficient to mitigate STZ-induced DCM through attenuation of oxidative stress, aberrant cell signaling and inflammation, suggesting a cross-organ mechanism by which exercise training improves cardiac function in diabetes. PMID:25504759

A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development.

PubMed

Ding, Mengmeng; Jin, Li; Xie, Lin; Park, So Hyun; Tong, Yixin; Wu, Di; Chhabra, A Bobby; Fu, Zheng; Li, Xudong

2018-03-01

An autosomal-recessive inactivating mutation R272Q in the human intestinal cell kinase (ICK) gene caused profound multiplex developmental defects in human endocrine-cerebro-osteodysplasia (ECO) syndrome. ECO patients exhibited a wide variety of skeletal abnormalities, yet the underlying mechanisms by which ICK regulates skeletal development remained largely unknown. The goal of this study was to understand the structural and mechanistic basis underlying skeletal anomalies caused by ICK dysfunction. Ick R272Q knock-in transgenic mouse model not only recapitulated major ECO skeletal defects such as short limbs and polydactyly but also revealed a deformed spine with defective intervertebral disk. Loss of ICK function markedly reduced mineralization in the spinal column, ribs, and long bones. Ick mutants showed a significant decrease in the proliferation zone of long bones and the number of type X collagen-expressing hypertrophic chondrocytes in the spinal column and the growth plate of long bones. These results implicate that ICK plays an important role in bone and cartilage development by promoting chondrocyte proliferation and maturation. Our findings provided new mechanistic insights into the skeletal phenotype of human ECO and ECO-like syndromes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terespolsky, D.; Siegel-Bartelt, J.; Weksberg, R.

Simpson-Golabi Behmel syndrome (SGBS) is an X-linked disorder characterized by pre- and postnatal macrosomia, minor facial anomalies, and variable visceral, skeletal, and neurological abnormalities. Since its first description by Simpson et al., a wide clinical range of cases has been reported. There is great variability in severity, ranging from a mild form associated with long-term survival to an early lethal form with multiple congenital anomalies and severe mental retardation. In 8 reported families, affected individuals died in infancy. Here we present 4 maternally related, male cousins with a severe variant of SGBS. One of these males was aborted therapeutically atmore » 19 weeks of gestation following the detection of multicystic kidneys on ultrasound. The 3 liveborn males were hydropic at birth with a combination of craniofacial anomalies including macrocephaly; apparently low-set, posteriorly angulated ears; hypertelorism; short, broad nose with anteverted nares; large mouth with thin upper vermilion border; prominent philtrum; high-arched or cleft palate; short neck; redundant skin; hypoplastic nails; skeletal defects involving upper and lower limbs; gastrointestinal and genitourinary anomalies. All 3 patients were hypotonic and neurologically impaired from birth. With the exception of a trilobate left lung in one patient, the cardiorespiratory system was structurally normal. All patients died within the first 8 weeks of life of multiple complications including pneumonia and sepsis. Two SGBS kindreds, with moderate expression of the condition, have been mapped to Xq27. It is not known whether severe, familiar cases, such as ours, are genetically distinct from and map to another locus. Final resolution of the genetic basis of the phenotypic variability in SGBS must await cloning and mutation analysis of the SGBS gene(s). 21 refs., 4 figs., 1 tab.« less

Craniofacial Duplication: A Case Report

PubMed Central

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-01-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature. PMID:24179933

Craniofacial duplication: a case report.

PubMed

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-09-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature.

Unfavourable results with distraction in craniofacial skeleton

PubMed Central

Agarwal, Rajiv

2013-01-01

Distraction osteogenesis has revolutionised the management of craniofacial abnormalities. The technique however requires precise planning, patient selection, execution and follow-up to achieve consistent and positive results and to avoid unfavourable results. The unfavourable results with craniofacial distraction stem from many factors ranging from improper patient selection, planning and use of inappropriate distraction device and vector. The present study analyses the current standards and techniques of distraction and details in depth the various errors and complications that may occur due to this technique. The commonly observed complications of distraction have been detailed along with measures and suggestions to avoid them in clinical practice. PMID:24501455

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An assessment of the compliance of systematic review articles published in craniofacial surgery with the PRISMA statement guidelines: A systematic review.

PubMed

Pidgeon, Thomas Edward; Wellstead, Georgina; Sagoo, Harkiran; Jafree, Daniyal J; Fowler, Alexander J; Agha, Riaz A

2016-10-01

Systematic review evidence is increasing within craniofacial surgery. Compliance with recognised reporting guidelines for systematic review evidence has not been assessed. To assess the compliance of systematic reviews published in craniofacial journals with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting criteria. Thomson Reuters impact factor was used to identify three top craniofacial journals. A search for all systematic review articles published in these journals from 1st May 2010 to 30th April 2015 was conducted using MEDLINE PubMed. Two independent researchers assessed each study for inclusion and performed the data extraction. Data included the article reference information; the pathology and interventions examined and compliance of each review article with the PRISMA checklist. 97 studies were returned by the search. 62 studies proceeded to data extraction. The mean percentage of applicable PRISMA items that were met across all studies was 72.5% (range 28.6-96.2%). The area of poorest compliance was with the declaration of a study protocol (19.4% of studies). Only 37.1% of studies declared their source of funding. Compliance of systematic review articles within craniofacial surgery with areas of the PRISMA checklist could be improved. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The Public Recognizes Plastic Surgeons as Leading Experts in the Treatment of Congenital Cleft and Craniofacial Anomalies.

PubMed

Denadai, Rafael; Samartine Junior, Hugo; Denadai, Rodrigo; Raposo-Amaral, Cassio Eduardo

2015-11-01

The aim of this study is to assess the public perception of plastic surgeons (PS) as craniofacial surgery specialists. Members of the public (N = 1514) were asked to choose 1 or 2 specialists that they perceived to be an expert for 13 craniofacial surgery-related scenarios. Response patterns were distributed as "plastic surgeon alone" (PS alone), "PS combined with other specialists", or "no plastic surgeon" (No PS). Sociodemographic data, previous plastic surgery contact, and source of reported information were also collected. "Plastic surgeon alone" was significantly (all P < 0.05) more recognized as experts than all other response patterns particularly in congenital anomalies-related scenarios (83.33%). There was a significantly (all P < 0.05) poor understanding of the role of PSs in head/neck infection management, chronic facial palsy management, dental disease management, head and neck cancer surgery, vascular malformation surgery, and facial fracture surgery. Sex, age, education level, health care professional, prior plastic surgery contact, and source of reported information were not significant (all P < 0.05) determinants of "PS" as the response in bivariate and multivariate analyses. Public recognized PSs as experts primarily in treatment of congenital cleft and craniofacial anomalies, but as the overall scope of craniofacial surgery practice was poorly understood and known, improved public education is needed.

Application of Computer-Assisted Design and Manufacturing-Fabricated Artificial Bone in the Reconstruction of Craniofacial Bone Defects.

PubMed

Liang, Weiqiang; Yao, Yuanyuan; Huang, Zixian; Chen, Yuhong; Ji, Chenyang; Zhang, Jinming

2016-07-01

The purpose of this study was to evaluate the clinical application of individual craniofacial bone fabrications using computer-assisted design (CAD)-computer-assisted manufacturing technology for the reconstruction of craniofacial bone defects. A total of 8 patients diagnosed with craniofacial bone defects were enrolled in this study between May 2007 and August 2010. After computed tomography scans were obtained, the patients were fitted with artificial bone that was created using CAD software, rapid prototyping technology, and epoxy-methyl acrylate resin and hydroxyapatite materials. The fabrication was fixed to the defect area with titanium screws, and soft tissue defects were repaired if necessary. The fabrications were precisely fixed to the defect areas, and all wounds healed well without any serious complications except for 1 case with intraoral incision dehiscence, which required further treatment. Postoperative curative effects were retrospectively observed after 6 to 48 months, acceptable anatomic and cosmetic outcomes were obtained, and no rejections or other complications occurred. The use of CAD-computer-assisted manufacturing technology-assisted epoxy-methyl acrylate resin and hydroxyapatite composite artificial bone to treat patients with craniofacial bone defects could enable the precise reconstruction of these defects and obtain good anatomic and cosmetic outcomes. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The influence of craniofacial to standing height proportion on perceived attractiveness.

PubMed

Naini, F B; Cobourne, M T; McDonald, F; Donaldson, A N A

2008-10-01

An idealised male image, based on Vitruvian Man, was created. The craniofacial height was altered from a proportion of 1/6 to 1/10 of standing height, creating 10 images shown in random order to 89 observers (74 lay people; 15 clinicians), who ranked the images from the most to the least attractive. The main outcome was the preference ranks of image attractiveness given by the observers. Linear regressions were used to assess what influences the choice for the most and the least attractive images, followed by a multivariate rank ordinal logistic regression to test the influence of age, gender, ethnicity and professional status of the observer. A craniofacial height to standing height proportion of 1/7.5 was perceived as the most attractive (36%), followed by a proportion of 1/8 (26%). The images chosen as most attractive by more than 10% of observers had a mean proportion of 1/7.8(min=1/7; max=1/8.5). The images perceived as most unattractive had a proportion of 1/6 and 1/10. The choice of images was not influenced by the age, gender, ethnicity or professional status of the observers. The ideal craniofacial height to standing height proportion is in the range 1/7 to 1/8.5. This finding should be considered when planning treatment to alter craniofacial or facial height.

Current and emerging basic science concepts in bone biology: implications in craniofacial surgery.

PubMed

Oppenheimer, Adam J; Mesa, John; Buchman, Steven R

2012-01-01

Ongoing research in bone biology has brought cutting-edge technologies into everyday use in craniofacial surgery. Nonetheless, when osseous defects of the craniomaxillofacial skeleton are encountered, autogenous bone grafting remains the criterion standard for reconstruction. Accordingly, the core principles of bone graft physiology continue to be of paramount importance. Bone grafts, however, are not a panacea; donor site morbidity and operative risk are among the limitations of autologous bone graft harvest. Bone graft survival is impaired when irradiation, contamination, and impaired vascularity are encountered. Although the dura can induce calvarial ossification in children younger than 2 years, the repair of critical-size defects in the pediatric population may be hindered by inadequate bone graft donor volume. The novel and emerging field of bone tissue engineering holds great promise as a limitless source of autogenous bone. Three core constituents of bone tissue engineering have been established: scaffolds, signals, and cells. Blood supply is the sine qua non of these components, which are used both individually and concertedly in regenerative craniofacial surgery. The discerning craniofacial surgeon must determine the proper use for these bone graft alternatives, while understanding their concomitant risks. This article presents a review of contemporary and emerging concepts in bone biology and their implications in craniofacial surgery. Current practices, areas of controversy, and near-term future applications are emphasized.

Sh3pxd2b Mice Are a Model for Craniofacial Dysmorphology and Otitis Media

PubMed Central

Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E.; Zheng, Qing Y.

2011-01-01

Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2bnee) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2bnee mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2bnee mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2bnee) mirrors craniofacial dysmorphology and otitis media in humans. PMID:21818352

MicroRNA in Skeletal Muscle: Its Crucial Roles in Signal Proteins, Mus cle Fiber Type, and Muscle Protein Synthesis.

PubMed

Zhang, Jing; Liu, Yu Lan

2017-01-01

Pork is one of the most economical sources of animal protein for human consumption. Meat quality is an important economic trait for the swine industry, which is primarily determined by prenatal muscle development and postnatal growth. Identification of the molecular mechanisms underlying skeletal muscle development is a key priority. MicroRNAs (miRNAs) are a class of small noncoding RNAs that have emerged as key regulators of skeletal muscle development. A number of muscle-related miRNAs have been identified by functional gain and loss experiments in mouse model. However, determining miRNA-mRNA interactions involved in pig skeletal muscle still remains a significant challenge. For a comprehensive understanding of miRNA-mediated mechanisms underlying muscle development, miRNAome analyses of pig skeletal muscle have been performed by deep sequencing. Additionally, porcine miRNA single nucleotide polymorphisms have been implicated in muscle fiber types and meat quality. The present review provides an overview of current knowledge on recently identified miRNAs involved in myogenesis, muscle fiber type and muscle protein metabolism. Undoubtedly, further systematic understanding of the functions of miRNAs in pig skeletal muscle development will be helpful to expand the knowledge of basic skeletal muscle biology and be beneficial for the genetic improvement of meat quality traits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of hypodynamic simulations on the skeletal system of monkeys

NASA Technical Reports Server (NTRS)

Young, D. R.; Tremor, J. W.

1977-01-01

A research and development program was undertaken to evaluate the skeletal losses of subhuman primates in hypodynamic environments. The goals of the program are: (1) to uncover the mechanisms by which weightlessness affects the skeletal system; (2) to determine the consequences and reversibility of bone mineral losses; and (3) to acquire a body of data needed to formulate an appropriate countermeasure program for the prevention of skeletal deconditioning. Space flight experiment simulation facilities are under development and will be tested for their capability in supporting certain of the requirements for these investigations.

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... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and..., Scientific Review Branch, National Institute of Dental and Craniofacial Research, One Democracy Plaza, Room...

77 FR 23488 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... unwarranted invasion of personal privacy. Name of Committee: National Advisory Dental and Craniofacial...

78 FR 7794 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and...: National Institute of Dental and Craniofacial Research Special Emphasis Panel; R34/U01 Grant Application...

75 FR 62553 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and..., National Institute of Dental and Craniofacial Research, One Democracy Plaza, Room 670, Bethesda, MD 20892...

75 FR 2150 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... Dental and Craniofacial Research Special Emphasis Panel; Review R13. Date: February 19, 2010. Time: 2 p.m...: Mary Kelly, Scientific Review Officer, Scientific Review Branch, National Inst. of Dental...

76 FR 5183 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act.... Krishnaraju, PhD, MS, Scientific Review Officer, Scientific Review Branch, National Inst. of Dental...

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors.

PubMed

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Zehuan; Tan, Nguan Soon

2018-05-10

Skeletal muscle comprises 30⁻40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies.

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

PubMed Central

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Zehuan

2018-01-01

Skeletal muscle comprises 30–40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies. PMID:29747466

Predictors of sleep disordered breathing in children: the PANIC study.

PubMed

Ikävalko, Tiina; Närhi, Matti; Eloranta, Aino-Maija; Lintu, Niina; Myllykangas, Riitta; Vierola, Anu; Tuomilehto, Henri; Lakka, Timo; Pahkala, Riitta

2018-05-25

We studied longitudinally the associations of craniofacial morphology, mouth breathing, orthodontic treatment, and body fat content with the risk of having and developing sleep disordered breathing (SDB) in childhood. We hypothesized that deviant craniofacial morphology, mouth breathing, and adiposity predict SDB among children. The participants were 412 children 6-8 years of age examined at baseline and 329 children aged 9-11 years re-examined at an average 2.2-year follow-up. An experienced orthodontist evaluated facial proportions, dental occlusion, soft tissue structures, and mode of breathing and registered malocclusions in orthodontic treatment. Body fat percentage was assessed by dual-energy X-ray absorptiometry and SDB symptoms by a questionnaire. Children with SDB more likely had convex facial profile, increased lower facial height, mandibular retrusion, tonsillar hypertrophy, and mouth breathing at baseline and convex facial profile, mandibular retrusion, and mouth breathing at follow-up than children without SDB at these examinations. Male gender and body adiposity, mouth breathing, and distal molar occlusion at baseline were associated with SDB later in childhood. Adipose tissue under the chin, mandibular retrusion, vertically large or normal throat and malocclusion in orthodontic treatment at baseline predicted developing SDB during follow-up of among children without SDB at baseline. We could not conduct polysomnographic examinations to define sleep disturbances. Instead, we used a questionnaire filled out by the parents to assess symptoms of SDB. The results indicate that among children, deviant craniofacial morphology, mouth breathing, body adiposity, and male gender seem to have implications in the pathophysiology of SDB.

Craniofacial and upper airway morphology in pediatric sleep-disordered breathing and changes in quality of life with rapid maxillary expansion.

PubMed

Katyal, Vandana; Pamula, Yvonne; Daynes, Cathal N; Martin, James; Dreyer, Craig W; Kennedy, Declan; Sampson, Wayne J

2013-12-01

The association between pediatric sleep-disordered breathing caused by upper airway obstruction and craniofacial morphology is poorly understood and contradictory. The aims of this study were to evaluate the prevalence of children at risk for sleep-disordered breathing, as identified in an orthodontic setting by validated screening questionnaires, and to examine associations with their craniofacial and upper airway morphologies. A further aim was to assess the change in quality of life related to sleep-disordered breathing for affected children undergoing rapid maxillary expansion to correct a palatal crossbite or widen a narrow maxilla. A prospective case-control study with children between 8 and 17 years of age (n = 81) at an orthodontic clinic was undertaken. The subjects were grouped as high risk or low risk for sleep-disordered breathing based on the scores from a validated 22-item Pediatric Sleep Questionnaire and the Obstructive Sleep Apnea-18 Quality of Life Questionnaire. Variables pertaining to a screening clinical examination, cephalometric assessment, and dental cast analysis were tested for differences between the 2 groups at baseline. Ten children who underwent rapid maxillary expansion were followed longitudinally until removal of the appliance approximately 9 months later with a repeated Obstructive Sleep Apnea-18 Quality of Life Questionnaire. All data were collected blinded to the questionnaire results. The frequency of palatal crossbite involving at least 3 teeth was significantly higher in the high-risk group at 68.2%, compared with the low-risk group at 23.2% (P <0.0001). Average quality of life scores in the high-risk group indicated reduced quality of life related to sleep-disordered breathing by 16% compared with children in the low-risk group at baseline (P <0.0001). Cephalometrically, mean inferior airway space, posterior nasal spine to adenoidal mass distance, and adenoidal mass to soft palate distance were reduced in the high-risk group compared with the low-risk group by 1.87 mm (P <0.03), 2.82 mm (P <0.04), and 2.13 mm (P <0.03), respectively. The mean maxillary intercanine, maxillary interfirst premolar, maxillary interfirst molar, mandibular intercanine, and mandibular interfirst premolar widths were reduced in the high-risk group compared with the low-risk group by 4.22 mm (P <0.0001), 3.92 mm (P <0.0001), 4.24 mm (P <0.0001), 1.50 mm (P <0.01), and 1.84 mm (P <0.01), respectively. Children treated with rapid maxillary expansion showed an average improvement of 14% in quality of life scores in the high-risk group compared with the low-risk group, which showed a slight worsening in quality of life related to sleep-disordered breathing by an average of 1% (P <0.04), normalizing the quality of life scores in the high-risk children to the baseline scores compared with the low-risk group. Children at high risk for sleep-disordered breathing are characterized by reduced quality of life, reduced nasopharyngeal and oropharyngeal sagittal dimensions, palatal crossbite, and reduced dentoalveolar transverse widths in the maxillary and mandibular arches. No sagittal or vertical craniofacial skeletal cephalometric predictors were identified for children at high risk for sleep-disordered breathing. In the short term, rapid maxillary expansion might aid in improvement of the quality of life for children with a narrow maxilla in the milder end of the sleep-disordered breathing spectrum. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

The oral and craniofacial relevance of chemically modified RNA therapeutics.

PubMed

Elangovan, Satheesh; Kormann, Michael S D; Khorsand, Behnoush; Salem, Aliasger K

2016-01-01

Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy, and their combinations are currently being explored for oral and craniofacial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions.

The Oral and Craniofacial Relevance of Chemically Modified RNA Therapeutics

PubMed Central

Kormann, Michael S.D.; Khorsand, Behnoush

2016-01-01

Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy and its combinations are currently being explored for oral and cranio-facial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions. PMID:26896600

Family Members as Participants on Craniofacial Teams.

ERIC Educational Resources Information Center

Andrews, James; Seaver, Earl; Stevens, George; Whiteley, Joseph

1998-01-01

Family members (N=83) who participated in professional team staffing concerning treatment plans for their child with a craniofacial difference (typically, cleft lip and/or palate) were surveyed. Ninety-seven percent of respondents said they would choose to meet with the team on their next visit to the clinic. The role of early interventionists on…

76 FR 23612 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: May 23, 2011. Open: 8:30 a.m...

78 FR 50426 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

76 FR 51995 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: September 19, 2011. Open: 8:30...

77 FR 49820 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: September 21, 2012. Open: 8:30...

77 FR 50140 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

77 FR 29673 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

78 FR 24761 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: May 21, 2013. Open: 8:30 a.m...

76 FR 57748 - National Institute of Dental & Craniofacial Research Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

76 FR 79199 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

78 FR 45934 - The National Institute of Dental and Craniofacial Research (NIDCR) Strategic Plan Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-30

... a new strategic plan to guide the Institute's research efforts and priorities over the next six... areas identified below. (1) ``Transformative'' areas of research where new discoveries could have the greatest benefit for advancing dental, oral, and craniofacial research. (2) New technical capabilities or...

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

3D-Printing Technologies for Craniofacial Rehabilitation, Reconstruction, and Regeneration.

PubMed

Nyberg, Ethan L; Farris, Ashley L; Hung, Ben P; Dias, Miguel; Garcia, Juan R; Dorafshar, Amir H; Grayson, Warren L

2017-01-01

The treatment of craniofacial defects can present many challenges due to the variety of tissue-specific requirements and the complexity of anatomical structures in that region. 3D-printing technologies provide clinicians, engineers and scientists with the ability to create patient-specific solutions for craniofacial defects. Currently, there are three key strategies that utilize these technologies to restore both appearance and function to patients: rehabilitation, reconstruction and regeneration. In rehabilitation, 3D-printing can be used to create prostheses to replace or cover damaged tissues. Reconstruction, through plastic surgery, can also leverage 3D-printing technologies to create custom cutting guides, fixation devices, practice models and implanted medical devices to improve patient outcomes. Regeneration of tissue attempts to replace defects with biological materials. 3D-printing can be used to create either scaffolds or living, cellular constructs to signal tissue-forming cells to regenerate defect regions. By integrating these three approaches, 3D-printing technologies afford the opportunity to develop personalized treatment plans and design-driven manufacturing solutions to improve aesthetic and functional outcomes for patients with craniofacial defects.

3D-Printing Technologies for Craniofacial Rehabilitation, Reconstruction, and Regeneration

PubMed Central

Nyberg, Ethan L.; Farris, Ashley L.; Hung, Ben P.; Dias, Miguel; Garcia, Juan R.; Dorafshar, Amir H.; Grayson, Warren L.

2016-01-01

The treatment of craniofacial defects can present many challenges due to the variety of tissue-specific requirements and the complexity of anatomical structures in that region. 3D-printing technologies provide clinicians, engineers and scientists with the ability to create patient-specific solutions for craniofacial defects. Currently, there are 3 key strategies that utilize these technologies to restore both appearance and function to patients: rehabilitation, reconstruction and regeneration. In rehabilitation, 3D-printing can be used to create prostheses to replace or cover damaged tissues. Reconstruction, through plastic surgery, can also leverage 3D-printing technologies to create custom cutting guides, fixation devices, practice models and implanted medical devices to improve patient outcomes. Regeneration of tissue attempts to replace defects with biological materials. 3D-printing can be used to create either scaffolds or living, cellular constructs to signal tissue-forming cells to regenerate defect regions. By integrating these three approaches, 3D-printing technologies afford the opportunity to develop personalized treatment plans and design-driven manufacturing solutions to improve aesthetic and functional outcomes for patients with craniofacial defects. PMID:27295184