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Sample records for human craniofacial disorders

  1. Modeling human craniofacial disorders in Xenopus.

    PubMed

    Dubey, Aditi; Saint-Jeannet, Jean-Pierre

    2017-03-01

    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. 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. 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.

  2. Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders.

    PubMed

    Brugmann, S A; Powder, K E; Young, N M; Goodnough, L H; Hahn, S M; James, A W; Helms, J A; Lovett, M

    2010-03-01

    Mammals and birds have common embryological facial structures, and appear to employ the same molecular genetic developmental toolkit. We utilized natural variation found in bird beaks to investigate what genes drive vertebrate facial morphogenesis. We employed cross-species microarrays to describe the molecular genetic signatures, developmental signaling pathways and the spectrum of transcription factor (TF) gene expression changes that differ between cranial neural crest cells in the developing beaks of ducks, quails and chickens. Surprisingly, we observed that the neural crest cells established a species-specific TF gene expression profile that predates morphological differences between the species. A total of 232 genes were differentially expressed between the three species. Twenty-two of these genes, including Fgfr2, Jagged2, Msx2, Satb2 and Tgfb3, have been previously implicated in a variety of mammalian craniofacial defects. Seventy-two of the differentially expressed genes overlap with un-cloned loci for human craniofacial disorders, suggesting that our data will provide a valuable candidate gene resource for human craniofacial genetics. The most dramatic changes between species were in the Wnt signaling pathway, including a 20-fold up-regulation of Dkk2, Fzd1 and Wnt1 in the duck compared with the other two species. We functionally validated these changes by demonstrating that spatial domains of Wnt activity differ in avian beaks, and that Wnt signals regulate Bmp pathway activity and promote regional growth in facial prominences. This study is the first of its kind, extending on previous work in Darwin's finches and provides the first large-scale insights into cross-species facial morphogenesis.

  3. Craniofacial ciliopathies: a new classification for craniofacial disorders

    PubMed Central

    Brugmann, Samantha A.; Cordero, Dwight R.; Helms, Jill A.

    2011-01-01

    Craniofacial dysmorphologies are some of the most variable and common defects affecting the population. Herein we examine a group of craniofacial disorders that are the result of defects in primary cilia; ubiquitous, microtubule based organelles that transduce molecular signals and facilitate the interactions between the cell and its environment. Based on the frequent appearance of craniofacial phenotypes in diseases born from defective primary cilia (ciliopathies) we propose a new class of craniofacial disorders referred to as craniofacial ciliopathies. We explore the most frequent phenotypes associated with ciliopathic conditions and the ciliary gene mutations responsible for craniofacial defects. Finally, we propose that some non-classified disorders may now be classified as craniofacial ciliopathies. PMID:21108387

  4. Regenerative Strategies for Craniofacial Disorders

    PubMed Central

    Garland, Catharine B.; Pomerantz, Jason H.

    2012-01-01

    Craniofacial disorders present markedly complicated problems in reconstruction because of the complex interactions of the multiple, simultaneously affected tissues. Regenerative medicine holds promise for new strategies to improve treatment of these disorders. This review addresses current areas of unmet need in craniofacial reconstruction and emphasizes how craniofacial tissues differ from their analogs elsewhere in the body. We present a problem-based approach to illustrate current treatment strategies for various craniofacial disorders, to highlight areas of need, and to suggest regenerative strategies for craniofacial bone, fat, muscle, nerve, and skin. For some tissues, current approaches offer excellent reconstructive solutions using autologous tissue or prosthetic materials. Thus, new “regenerative” approaches would need to offer major advantages in order to be adopted. In other tissues, the unmet need is great, and we suggest the greatest regenerative need is for muscle, skin, and nerve. The advent of composite facial tissue transplantation and the development of regenerative medicine are each likely to add important new paradigms to our treatment of craniofacial disorders. PMID:23248598

  5. 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.

  6. Heritability of the Human Craniofacial Complex.

    PubMed

    Šešelj, Maja; Duren, Dana L; Sherwood, Richard J

    2015-09-01

    Quantifying normal variation and the genetic underpinnings of anatomical structures is one of the main goals of modern morphological studies. However, the extent of genetic contributions to normal variation in craniofacial morphology in humans is still unclear. The current study addresses this gap by investigating the genetic underpinnings of normal craniofacial morphology. The sample under investigation consists of 75 linear and angular measurements spanning the entire craniofacial complex, recorded from lateral cephalographs of 1,379 participants in the Fels Longitudinal Study. Heritabilities for each trait were estimated using SOLAR, a maximum-likelihood variance components approach utilizing all pedigree information for parameter estimation. Trait means and mean effects of the covariates age, sex, age(2) , sex × age, and sex × age(2) were simultaneously estimated in the analytic models. All traits of the craniofacial complex were significantly heritable. Heritability estimates ranged from 0.10 to 0.60, with the majority being moderate. It is important to note that we found similar ranges of heritability occurring across the different functional/developmental components of the craniofacial complex, the splanchnocranium, the basicranium, and the neurocranium. This suggests that traits from different regions of the craniofacial complex are of comparable utility for the purposes of population history and phylogeny reconstruction. At the same time, this genetic influence on craniofacial morphology signals a caution to researchers of nongenetic studies to consider the implications of this finding when selecting samples for study given their project design and goals. © 2015 Wiley Periodicals, Inc.

  7. A review of craniofacial disorders caused by spliceosomal defects.

    PubMed

    Lehalle, D; Wieczorek, D; Zechi-Ceide, R M; Passos-Bueno, M R; Lyonnet, S; Amiel, J; Gordon, C T

    2015-11-01

    The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.

  8. Vertical Craniofacial Morphology and its Relation to Temporomandibular Disorders

    PubMed Central

    Bavia, Paula Furlan

    2016-01-01

    ABSTRACT Objectives This study investigated the association between craniofacial morphology and temporomandibular disorders in adults. The influence of different craniofacial morphologies on painful temporomandibular disorders was also evaluated. Material and Methods A total of 200 subjects were selected, including 100 with temporomandibular disorders (TMD) and 100 without TMD (control), diagnosed by research diagnostic criteria for temporomandibular disorders. All subjects were submitted to lateral cephalometric radiographs, and classified as brachyfacial, mesofacial, or dolichofacial by Ricketts’ analysis. Data were analysed by Tukey-Kramer and Chi-square tests. Results No association between craniofacial morphology and TMD was found (P = 0.6622). However, brachyfacial morphology influences the presence of painful TMD (P = 0.0077). Conclusions Craniofacial morphology is not related to temporomandibular disorders in general. PMID:27489610

  9. 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.

  10. Sleep deprivation sensitizes human craniofacial muscles.

    PubMed

    Kristiansen, Eva Szuchy; Nielsen, Louise Skou; Christensen, Siv Sofie; Botvid, Sofia Hedvig Christina; Nørgaard Poulsen, Jeppe; Gazerani, Parisa

    2017-06-01

    It is unknown whether and how sleep deprivation influences craniofacial muscle sensitivity in healthy humans. We investigated whether total sleep deprivation (TSD) and one night of recovery sleep (RS) can alter mechanical pain sensitivity in temporal and masseter muscles. Fifteen healthy volunteers participated in three consecutive sessions. Pressure pain thresholds were measured on the temporal and masseter muscles. Both temporal and masseter muscles became sensitized after 24 h of TSD. RS reversed the muscle sensitization.

  11. 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

  12. Symptoms of Sleep Disordered Breathing in Children with Craniofacial Malformations

    PubMed Central

    Moraleda-Cibrián, Marta; Edwards, Sean P.; Kasten, Steven J.; Berger, Mary; Buchman, Steven R.; O'Brien, Louise M.

    2014-01-01

    Study Objective: The purpose of this study was to investigate the frequency of sleep disordered breathing (SDB) symptoms in a clinical sample of children with congenital craniofacial malformations (CFM) followed at a tertiary medical center and non-selected for sleep problems. Methods: Cross-sectional study of 575 children aged 2-18 years followed at the Craniofacial Anomalies Program between March 2007 and May 2011. The Sleep-Related Breathing Disturbance scale of the Pediatric Sleep Questionnaire was used to screen for SDB, snoring, and sleepiness. A cutoff value ≥ 0.33 of the total answered questions identified children with positive screening for SDB symptoms. Results: Overall, 25% of children screened positive for SDB, 28% for snoring, and 20% for sleepiness. In children with non-syndromic CFM, those with Robin sequence had the highest frequency of SDB, snoring, and sleepiness (43%, 44%, and 38%, respectively). In children with syndromic CFM, velocardiofacial/ DiGeorge syndrome had the highest frequency of SDB and sleepiness (48% and 43%, respectively). Children with Treacher Collins had the highest frequency of snoring (83%). The presence of cleft palate was not associated with an increased frequency of SDB symptoms. Nevertheless, children with syndromic CFM, compared to those with non-syndromic CFM, had a higher SDB score (0.27 ± 0.21 vs.0.21 ± 0.19, p = 0.003) and were more likely to have sleepiness (26% vs. 18%, p = 0.05). Conclusions: Congenital craniofacial malformations in children are associated with high risk for SDB symptoms. Our findings should encourage a high index of suspicion for SDB in children with CFM, with a low threshold for further testing and close follow-up. Citation: Moraleda-Cibrián M; Edwards SP; Kasten SJ; Berger M; Buchman SR; O'Brien LM. Symptoms of sleep disordered breathing in children with craniofacial malformations. J Clin Sleep Med 2014;10(3):307-312. PMID:24634629

  13. Craniofacial Syndromes and Sleep-Related Breathing Disorders

    PubMed Central

    Tan, Hui-Leng; Kheirandish-Gozal, Leila; Abel, François; Gozal, David

    2015-01-01

    Summary Children with craniofacial syndromes are at risk of sleep disordered breathing, the most common being obstructive sleep apnea. Midface hypoplasia in children with craniosynostosis and glossoptosis in children with Pierre Robin syndrome are well recognized risk factors, but the etiology is often multifactorial and many children have multilevel airway obstruction. We examine the published evidence and explore the current management strategies in these complex patients. Some treatment modalities are similar to those used in otherwise healthy children such as as adenotonsillectomy, positive pressure ventilation and in the refractory cases, tracheostomy. However, there are some distinct approaches such as nasopharyngeal airways, tongue lip adhesion, mandibular distraction osteogenesis in children with Pierre Robin sequence, and midface advancement in children with craniosynostoses. Clinicians should have a low threshold for referral for evaluation of sleep-disordered-breathing in these patients. PMID:26454241

  14. 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.

  15. Utility of screening for obstructive sleep apnea syndrome in children with craniofacial disorders.

    PubMed

    Cielo, Christopher M; Silvestre, Jason; Paliga, J Thomas; Maguire, Meg; Gallagher, Paul R; Marcus, Carole L; Taylor, Jesse A

    2014-09-01

    Children with craniofacial disorders are at increased risk for obstructive sleep apnea syndrome. Methods for diagnosing obstructive sleep apnea syndrome in this population remain controversial. Sleep studies are the criterion standard but are impractical for all patients. The utility of obstructive sleep apnea syndrome questionnaires such as the Pediatric Sleep Questionnaire is unknown in children with craniofacial disorders. The authors hypothesized that the Pediatric Sleep Questionnaire would be a sensitive tool for detecting obstructive sleep apnea syndrome in children with craniofacial abnormalities. A retrospective review of consecutive children with diagnosed craniofacial disorders who both completed the Pediatric Sleep Questionnaire and underwent polysomnography was performed. Demographics, Pediatric Sleep Questionnaire score, and polysomnographic data were recorded. Statistical analysis included calculation of sensitivity, specificity, positive predictive value, and negative predictive value for the Pediatric Sleep Questionnaire. Eighty-three children aged 2 to 18 years were included in the study. Of these, 44 (53.0 percent) screened positive on the Pediatric Sleep Questionnaire and 23 (27.7 percent) had polysomnographic evidence of obstructive sleep apnea syndrome, but the sensitivity of the Pediatric Sleep Questionnaire for detecting obstructive sleep apnea syndrome in this sample was only 0.57 and the specificity was 0.48. Positive predictive value and negative predictive value were 0.30 and 0.74, respectively. The correlation between the apnea hypopnea index and Pediatric Sleep Questionnaire score was 0.152 (p = 0.17). A substantial portion of craniofacial patients referred for polysomnography was found to have obstructive sleep apnea syndrome. However, the Pediatric Sleep Questionnaire is not a good screening tool for obstructive sleep apnea syndrome in children with craniofacial conditions. More research is needed to determine which patients with

  16. A multinational deployment of 3D laser scanning to study craniofacial dysmorphology in fetal alcohol spectrum disorders

    NASA Astrophysics Data System (ADS)

    Rogers, Jeff; Wernert, Eric; Moore, Elizabeth; Ward, Richard; Wetherill, Leah F.; Foroud, Tatiana

    2007-01-01

    Craniofacial anthropometry (the measurement and analysis of head and face dimensions) has been used to assess and describe abnormal craniofacial variation (dysmorphology) and the facial phenotype in many medical syndromes. Traditionally, anthropometry measurements have been collected by the direct application of calipers and tape measures to the subject's head and face, and can suffer from inaccuracies due to restless subjects, erroneous landmark identification, clinician variability, and other forms of human error. Three-dimensional imaging technologies promise a more effective alternative that separates the acquisition and measurement phases to reduce these variabilities while also enabling novel measurements and longitudinal analysis of subjects. Indiana University (IU) is part of an international consortium of researchers studying fetal alcohol spectrum disorders (FASD). Fetal alcohol exposure results in predictable craniofacial dysmorphologies, and anthropometry has been proven to be an effective diagnosis tool for the condition. IU is leading a project to study the use of 3D surface scanning to acquire anthropometry data in order to more accurately diagnose FASD, especially in its milder forms. This paper describes our experiences in selecting, verifying, supporting, and coordinating a set of 3D scanning systems for use in collecting facial scans and anthropometric data from around the world.

  17. The role of physical therapy in craniofacial pain disorders: an adjunct to dental pain management.

    PubMed

    Heinrich, S

    1991-01-01

    Treatment of craniofacial pain disorders is often complicated by diverse factors such as acute or chronic trauma and persistent postural changes. In addition, emotional issues and life stress often cloud the recovery process. Physical therapists, with their diverse knowledge base and highly competent treatment skills, can be quite effective in assisting dentists and physicians with management of the many difficult upper quarter and craniofacial pain syndromes. This article reviews the role of myofascial and craniosacral dysfunction, as well as the function of posture, tension, and stress in the development of these syndromes. Additionally, it provides a comprehensive overview of the many evaluative techniques and treatment options that can be provided by today's physical therapists.

  18. Craniofacial Morphology Affects Bite Force in Patients with Painful Temporomandibular Disorders.

    PubMed

    Bavia, Paula Furlan; Vilanova, Larissa Soares Reis; Garcia, Renata Cunha Matheus Rodrigues

    2016-01-01

    Craniofacial morphology affects masticatory performance in healthy dentate subjects, but little is known about its effects in patients with painful temporomandibular disorders (TMDs). Forty-eight female patients (mean age of 28±5.8 years) with painful TMDs underwent lateral cephalometric radiography. Using Ricketts' cephalometric analysis and the Vert method, subjects were assigned to three groups according to their craniofacial morphology: brachyfacial (n=22), mesofacial (n=13), and dolichofacial (n=13). Research diagnostic criteria for TMD were used to confirm the TMD diagnosis for each patient. Pain intensity was reported by each patient based on a visual analog scale (VAS). Maximum bite force (MBF) was measured with pressure sensors placed on the first molar site. Masticatory performance (MP) was assessed by chewing a silicone-based artificial material and determining the resulting particle size by the sieve method. Chewing ability (CA) was evaluated for seven food types and analyzed by a VAS questionnaire. Data were analyzed by one-way ANOVA followed by a Tukey-Kramer test (p<0.05). MBF differed in each group, with brachyfacial patients having the highest MBF values. There was no difference in MP among the groups. The groups differed only in their ability to chew one of the seven evaluated food types. In summary, craniofacial morphology affects the MBF without impairing MP or CA in patients with painful TMDs.

  19. Orientation of craniofacial planes and temporomandibular disorder in young adults with normal occlusion.

    PubMed

    Ciancaglini, R; Colombo-Bolla, G; Gherlone, E F; Radaelli, G

    2003-09-01

    The aim of this study was to investigate the relationship between orientation of craniofacial planes relative to the true horizontal and temporomandibular disorder (TMD), in normal occlusion. Fourteen university dental students, with full natural dentition and bilateral Angle Class I occlusion, who exhibited signs and symptoms of TMD, were compared with 14 age- and sex-matched healthy controls. Frontal and lateral photographs were taken in natural head position with the subject standing up, clenching a Fox plane and having a facial arch positioned. Photographs were examined by a standardized image analysis. Inter-pupillary axis, Frankfurt, occlusal and Camper planes were evaluated. In frontal view, the Frankfurt plane was right rotated relative to the true horizontal both in TMD subjects (P < 0.01) and controls (P < 0.05), but rotation was larger in TMD subjects (mean difference between groups, 1.1 degrees, 95% confidence interval, 95% CI, 0.2-2.0 degrees ). No significant deviation from the horizontal or difference between groups was observed for the interpupillary axis and occlusal plane. In lateral view, the Frankfurt plane was upward-orientated relative to the true horizontal in TMD group (mean angular deviation 2.8 degrees, 95% CI, 1.0-4.6 degrees ). The occlusal and Camper planes were downward-orientated in both groups (P < 0.0001), but inclination of occlusal plane tended to be smaller in TMD subjects (mean difference between groups, -3.8 degrees, 95% CI, -7.6-0.1 degrees ). Angles between any craniofacial planes did not significantly differ between groups. The findings show that in young adults with normal occlusion, a weak association exists between the orientation of craniofacial planes in natural head position and signs and symptoms of TMD. Furthermore, they suggest that, within this population, TMD might be mainly associated with head posture rather than with craniofacial morphology.

  20. Utilizing the chicken as an animal model for human craniofacial ciliopathies

    PubMed Central

    Schock, Elizabeth N.; Chang, Ching-Fang; Youngworth, Ingrid A.; Davey, Megan G.; Delany, Mary E.; Brugmann, Samantha A.

    2015-01-01

    The chicken has been a particularly useful model for the study of craniofacial development and disease for over a century due to their relatively large size, accessibility, and amenability for classical bead implantation and transplant experiments. Several naturally occurring mutant lines with craniofacial anomalies also exist and have been heavily utilized by developmental biologist for several decades. Two of the most well known lines, talpid2 (ta2) and talpid3 (ta3), represent the first spontaneous mutants to have the causative genes identified. Despite having distinct genetic causes, both mutants have recently been identified as ciliopathic. Excitingly, both of these mutants have been classified as models for human craniofacial ciliopathies: Oral-facial-digital syndrome (ta2) and Joubert syndrome (ta3). Herein, we review and compare these two models of craniofacial disease and highlight what they have revealed about the molecular and cellular etiology of ciliopathies. Furthermore, we outline how applying classical avian experiments and new technological advances (transgenics and genome editing) with naturally occurring avian mutants can add a tremendous amount to what we currently know about craniofacial ciliopathies. PMID:26597494

  1. Phenotypic evolution of human craniofacial morphology after admixture: a geometric morphometrics approach.

    PubMed

    Martínez-Abadías, Neus; González-José, Rolando; González-Martín, Antonio; Van der Molen, Silvina; Talavera, Arturo; Hernández, Patricia; Hernández, Miquel

    2006-03-01

    An evolutionary, diachronic approach to the phenotypic craniofacial pattern arisen in a human population after high levels of admixture and gene flow was achieved by means of geometric morphometrics. Admixture has long been studied after molecular data. Nevertheless, few efforts have been made to explain the morphological outcome in human craniofacial samples. The Spanish-Amerindian contact can be considered a good scenario for such an analysis. Here we present a comparative analysis of craniofacial shape changes observed between two putative ancestor groups, Spanish and precontact Aztecs, and two diachronic admixed groups, corresponding to early and late colonial periods from the Mexico's Central Valley. Quantitative shape comparisons of Amerindian, Spanish, and admixed groups were used to test the expectations of quantitative genetics for admixture events. In its simplest form, this prediction states that an admixed group will present phenotypic values falling between those of both parental groups. Results show that, in general terms, although the human skull is a complex, integrated structure, the craniofacial morphology observed fits the theoretical expectations of quantitative genetics. Thus, it is predictive of population structure and history. In fact, results obtained after the craniofacial analysis are in accordance with previous molecular and historical interpretations, providing evidence that admixture is a main microevolutionary agent influencing modern Mexican gene pool. However, expectations are not straightforward when moderate shape changes are considered. Deviations detected at localized structures, such as the upper and lower face, highlight the evolution of a craniofacial pattern exclusively inherent to the admixed groups, indicating that quantitative characters might respond to admixture in a complicated, nondirectional way. (c) 2005 Wiley-Liss, Inc.

  2. 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.

  3. Localization of the homolog of a mouse craniofacial mutant to human chromosome 18q11 and evaluation of linkage to human CLP and CPO

    SciTech Connect

    Griffith, A.J.; Burgess, D.L.; Kohrman, D.C.; Yu, J.

    1996-06-15

    The transgene-induced mutation 9257 and the spontaneous mutation twirler cause craniofacial and inner ear malformations and are located on mouse chromosome 18 near the ataxia locus ax. To map the human homolog of 9257, a probe from the transgene insertion site was used to screen a human genomic library. Analysis of a cross-hybridizing human clone identified a 3-kb conserved sequence block that does not appear to contain protein coding sequence. Analysis of somatic cell hybrid panels assigned the human locus to 18q11. The polymorphic microsatellite markers D18S1001 and D18S1002 were isolated from the human locus and mapped by linkage analysis using the CEPH pedigrees. The 9257 locus maps close to the centromeres of human chromosome 18q and mouse chromosome 18 at the proximal end of a conserved linkage group. To evaluate the role of this locus in human craniofacial disorders, linkage to D18S1002 was tested in 11 families with autosomal dominant nonsyndromic cleft lip and palate and 3 families with autosomal dominant cleft palate only. Obligatory recombinants were observed in 8 of the families, and negative lod scores from the other families indicated that these disorders are not linked to the chromosome 18 loci. 23 refs., 4 figs., 2 tabs.

  4. ID migraine questionnaire in temporomandibular disorders with craniofacial pain: a study by using a multidisciplinary approach.

    PubMed

    Di Paolo, Carlo; Di Nunno, Anna; Vanacore, Nicola; Bruti, Gianluca

    2009-08-01

    To evaluate the prevalence of migraine and related disability and the role of ID migraine questionnaire as a screening tool in patients with temporomandibular disorders (TMDs) and craniofacial pain (CFP). TMDs patients with CFP underwent stomatognathic (RDC/TMD criteria) and neurological visits (IHS criteria, 2004). ID migraine questionnaire and MIgraine Disability Assessment Scale (MIDAS) were also administered. Out of 45 patients, 69% met diagnosis of migraine plus chronic tension-type headache (CTTH); 9% presented CTTH and 20% were migraineurs. Out of 39 migraineurs who completed MIDAS, 56% presented the highest disability grade. Out of 37 patients who completed ID migraine questionnaire, 32 resulted affected by probable migraine with a diagnostic sensibility and specificity of 94% and 100%, respectively. Our findings showed a clinical association between TMDs and migraine. We support a clinical role of ID migraine and MIDAS in TMDs patients with CFP and we underline the importance of a multidisciplinary evaluation in this group of migraineurs.

  5. Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects.

    PubMed

    Loomes, Kathleen M; Stevens, Stacey A; O'Brien, Megan L; Gonzalez, Dorian M; Ryan, Matthew J; Segalov, Michelle; Dormans, Nicholas J; Mimoto, Mizuho S; Gibson, Joshua D; Sewell, William; Schaffer, Alyssa A; Nah, Hyun-Duck; Rappaport, Eric F; Pratt, Stephen C; Dunwoodie, Sally L; Kusumi, Kenro

    2007-10-01

    Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant reduction of mandibular height and decreased length of the [corrected] maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Thus, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders.

  6. Human Development Domain of the Ontology of Craniofacial Development and Malformation

    PubMed Central

    Mejino, Jose LV; Travillian, Ravensara S; Cox, Timothy C; Shapiro, Linda G; Brinkley, James F

    2017-01-01

    In this paper we describe an ontological scheme for representing anatomical entities undergoing morphological transformation and changes in phenotype during prenatal development. This is a proposed component of the Anatomical Transformation Abstraction (ATA) of the Foundational Model of Anatomy (FMA) Ontology that was created to provide an ontological framework for capturing knowledge about human development from the zygote to postnatal life. It is designed to initially describe the structural properties of the anatomical entities that participate in human development and then enhance their description with developmental properties, such as temporal attributes and developmental processes. This approach facilitates the correlation and integration of the classical but static representation of embryology with the evolving novel concepts of developmental biology, which primarily deals with the experimental data on the mechanisms of embryogenesis and organogenesis. This is important for describing and understanding the underlying processes involved in structural malformations. In this study we focused on the development of the lips and the palate in conjunction with our work on the pathogenesis and classification of cleft lip and palate (CL/P) in the FaceBase program. Our aim here is to create the Craniofacial Human Development Ontology (CHDO) to support the Ontology of Craniofacial Development and Malformation (OCDM), which provides the infrastructure for integrating multiple and disparate craniofacial data generated by FaceBase researchers.

  7. Facing up to the Challenges of Advancing Craniofacial Research

    PubMed Central

    Trainor, Paul A.; Richtsmeier, Joan T.

    2015-01-01

    Craniofacial anomalies are among the most common human birth defects and have considerable functional, aesthetic, and social consequences. The early developmental origin as well as the anatomical complexity of the head and face render these tissues prone to genetic and environmental insult. The establishment of craniofacial clinics offering comprehensive care for craniofacial patients at a single site together with international research networks focused on the origins and treatment of craniofacial disorders has led to tremendous advances in our understanding of the etiology and pathogenesis of congenital craniofacial anomalies. However, the genetic, environmental, and developmental sources of many craniofacial disorders remain unknown. To overcome this problem and further advance craniofacial research, we must recognize current challenges in the field and establish priority areas for study. We still need (i) a deeper understanding of variation during normal development and within the context of any disorder, (ii) improved genotyping and phenotyping and understanding of the impact of epigenetics, (iii) continued development of animal models and functional analyses of genes and variants, and (iv) integration of patient derived cells and tissues together with 3D printing and quantitative assessment of surgical outcomes for improved practice. Only with fundamental advances in each of these areas will we be able to meet the challenge of translating potential therapeutic and preventative approaches into clinical solutions and reduce the financial and emotional burden of craniofacial anomalies. PMID:25820983

  8. Sensitivity analysis of a validated subject-specific finite element model of the human craniofacial skeleton.

    PubMed

    Szwedowski, T D; Fialkov, J; Whyne, C M

    2011-01-01

    Developing a more complete understanding of the mechanical response of the craniofacial skeleton (CFS) to physiological loads is fundamental to improving treatment for traumatic injuries, reconstruction due to neoplasia, and deformities. Characterization of the biomechanics of the CFS is challenging due to its highly complex structure and heterogeneity, motivating the utilization of experimentally validated computational models. As such, the objective of this study was to develop, experimentally validate, and parametrically analyse a patient-specific finite element (FE) model of the CFS to elucidate a better understanding of the factors that are of intrinsic importance to the skeletal structural behaviour of the human CFS. An FE model of a cadaveric craniofacial skeleton was created from subject-specific computed tomography data. The model was validated based on bone strain measurements taken under simulated physiological-like loading through the masseter and temporalis muscles (which are responsible for the majority of craniofacial physiologic loading due to mastication). The baseline subject-specific model using locally defined cortical bone thicknesses produced the strongest correlation to the experimental data (r2 = 0.73). Large effects on strain patterns arising from small parametric changes in cortical thickness suggest that the very thin bony structures present in the CFS are crucial to characterizing the local load distribution in the CFS accurately.

  9. Craniofacial changes and symptoms of sleep-disordered breathing in healthy children.

    PubMed

    Pacheco, Maria Christina Thomé; Fiorott, Bruna Santos; Finck, Nathalia Silveira; Araújo, Maria Teresa Martins de

    2015-01-01

    The main cause of mouth breathing and sleep-disordered breathing (SDB) in childhood is associated with upper airway narrowing to varying degrees. The aim of this study was to assess the prevalence of morphological and functional craniofacial changes and the main clinical symptoms of SDB in healthy children. A cross-sectional observational study was conducted. A sample comprising 687 healthy schoolchildren, aged 7-12 years old and attending public schools, was assessed by medical history, clinical medical and dental examination, and respiratory tests. The self-perceived quality of life of mouth breathing children was obtained by a validated questionnaire. Out of the total sample, 520 children were nose breathers (NB) while 167 (24.3%) were mouth breathers (MB); 32.5% had severe hypertrophy of the palatine tonsils, 18% had a Mallampati score of III or IV, 26.1% had excessive overjet and 17.7% had anterior open bite malocclusion. Among the MB, 53.9% had atresic palate, 35.9% had lip incompetence, 33.5% reported sleepiness during the day, 32.2% often sneezed, 32.2% had a stuffy nose, 19.6% snored, and 9.4% reported having the feeling to stop breathing while asleep. However, the self-perception of their quality of life was considered good. High prevalence of facial changes as well as signs and symptoms of mouth breathing were found among health children, requiring early diagnosis and treatment to reduce the risk of SDB.

  10. Discovery and characterization of spontaneous mouse models of craniofacial dysmorphology

    PubMed Central

    Palmer, Kristina; Fairfield, Heather; Borgeia, Suhaib; Curtain, Michelle; Hassan, Mohamed G.; Dionne, Louise; Karst, Son Yong; Coombs, Harold; Reinholdt, Laura G.; Bergstrom, David E.; Donahue, Leah Rae; Cox, Timothy C.; Murray, Stephen A.

    2015-01-01

    Craniofacial abnormalities are among the most common features of human genetic syndromes and disorders. The etiology of these conditions is often complex, influenced by both genetic context and the environment. Frequently, craniofacial abnormalities present as part of a syndrome with clear comorbid phenotypes, providing additional insight into mechanisms of the causative gene or pathway. The mouse has been a key tool in our understanding of the genetic mechanisms of craniofacial development and disease, and can provide excellent models for human craniofacial abnormalities. While powerful genetic engineering tools in the mouse have contributed significantly our understanding of craniofacial development and dysmorphology, forward genetic approaches provide an unbiased means to identify new genes and pathways. Moreover, spontaneous mutations can occur on any number of genetic backgrounds, potentially revealing critical genes that require a specific genetic context. Here we report discovery and phenotyping of 43 craniofacial mouse models, derived primarily from a screen for spontaneous mutations in production colonies at the Jackson Laboratory. We identify the causative gene for 33 lines, including novel genes in pathways not previously connected to craniofacial development, and novel alleles of known genes that present with unique phenotypes. Together with our detailed characterization, this work provides a valuable gene discovery resource for the craniofacial community, and a rich source of mouse models for further investigation. PMID:26234751

  11. Cis-regulatory underpinnings of human GLI3 expression in embryonic craniofacial structures and internal organs.

    PubMed

    Abbasi, Amir A; Minhas, Rashid; Schmidt, Ansgar; Koch, Sabine; Grzeschik, Karl-Heinz

    2013-10-01

    The zinc finger transcription factor Gli3 is an important mediator of Sonic hedgehog (Shh) signaling. During early embryonic development Gli3 participates in patterning and growth of the central nervous system, face, skeleton, limb, tooth and gut. Precise regulation of the temporal and spatial expression of Gli3 is crucial for the proper specification of these structures in mammals and other vertebrates. Previously we reported a set of human intronic cis-regulators controlling almost the entire known repertoire of endogenous Gli3 expression in mouse neural tube and limbs. However, the genetic underpinning of GLI3 expression in other embryonic domains such as craniofacial structures and internal organs remain elusive. Here we demonstrate in a transgenic mice assay the potential of a subset of human/fish conserved non-coding sequences (CNEs) residing within GLI3 intronic intervals to induce reporter gene expression at known regions of endogenous Gli3 transcription in embryonic domains other than central nervous system (CNS) and limbs. Highly specific reporter expression was observed in craniofacial structures, eye, gut, and genitourinary system. Moreover, the comparison of expression patterns directed by these intronic cis-acting regulatory elements in mouse and zebrafish embryos suggests that in accordance with sequence conservation, the target site specificity of a subset of these elements remains preserved among these two lineages. Taken together with our recent investigations, it is proposed here that during vertebrate evolution the Gli3 expression control acquired multiple, independently acting, intronic enhancers for spatiotemporal patterning of CNS, limbs, craniofacial structures and internal organs.

  12. Mechanisms of craniofacial pain.

    PubMed

    Chichorro, Juliana Geremias; Porreca, Frank; Sessle, Barry

    2017-06-01

    Aim To provide an overview of mechanisms underlying craniofacial pain; to highlight peripheral and central adaptations that may promote chronification of pain in craniofacial pain states such as migraine and temporomandibular disorders (TMD). Background Pain is a common symptom associated with disorders involving craniofacial tissues including the teeth and their supporting structures, the temporomandibular joint and the muscles of the head. Most acute painful craniofacial conditions are easily recognized and well managed, but others, especially those that are chronic (e.g., migraine, TMD and trigeminal neuropathies), present clinical challenges. Preclinical studies have provided substantial information about the anatomical and physiological mechanisms related to the initiation and modulation of nociceptive signals in the trigeminal system. While knowledge of the mechanisms underlying chronic craniofacial pain remains limited, both clinical and preclinical investigations suggest that changes in afferent inputs to the brain as well as in brain structure and modulatory pathways occur in chronic pain. Collectively, these changes result in amplification of nociception that promotes and sustains craniofacial chronic pain states. Conclusions The increased understanding gained of the physiological and pathological processing of nociception in the trigeminal system has provided new perspectives for the mechanistic understanding of acute craniofacial pain conditions and the peripheral and central adaptations that are related to pain chronification. Such knowledge may contribute to improvements in currently available treatments as well as to the development of novel analgesic therapies.

  13. Shape covariation between the craniofacial complex and first molars in humans

    PubMed Central

    Polychronis, Georgios; Halazonetis, Demetrios J

    2014-01-01

    The occurrence of mutual genetic loci in morphogenesis of the face and teeth implies shape covariation between these structures. However, teeth finalize their shape at an early age, whereas the face grows and is subjected to environmental influences for a prolonged period; it is therefore conceivable that covariation might modulate with age. Here we investigate the extent of this covariation in humans by measuring the 3D shape of the occlusal surface of the permanent first molars and the shape of the craniofacial complex from lateral radiographs, at two maturations stages. A sample of Greek subjects was divided into two groups (110 adult, 110 prepubertal) with equally distributed gender. The occlusal surfaces of the right first molars were 3D scanned from dental casts; 265 and 274 landmarks (including surface and curve semilandmarks) were digitized on the maxillary and mandibular molars, respectively. The corresponding lateral cephalometric radiographs were digitized with 71 landmarks. Geometric morphometric methods were used to assess shape variation and covariation. The vertical dimension of the craniofacial complex was the main parameter of shape variation, followed by anteroposterior deviations. The male craniofacial complex was larger (4.0–5.7%) and was characterized by a prominent chin and clockwise rotation of the cranial base (adult group only). Allometry was weak and statistically significant only when examined for the sample as a whole (percent variance explained: 2.1%, P = 0.0002). Covariation was statistically significant only between the lower first molar and the craniofacial complex (RV = 14.05%, P = 0.0099, and RV = 12.31%, P = 0.0162, for the prepubertal and adult groups, respectively). Subtle age-related covariation differences were noted, indicating that environmental factors may influence the pattern and strength of covariation. However, the main pattern was similar in both groups: a class III skeletal pattern (relative maxillary retrusion and

  14. Growth hormone therapy and craniofacial bones: a comprehensive review.

    PubMed

    Litsas, G

    2013-09-01

    Growth hormone (GH) has significant effects on linear bone growth, bone mass and bone metabolism. The primary role of GH supplementation in children with GH deficiency, those born small for gestational age or with other types of disorders in somatic development is to increase linear growth. However, GH therapy seems to elicit varying responses in the craniofacial region. Whereas the effects of GH administration on somatic development are well documented, comparatively little is known of its effects on the craniofacial region. The purpose of this review was to search the literature and compile results from both animal and human studies related to the impact of GH on craniofacial growth.

  15. Craniofacial changes and symptoms of sleep-disordered breathing in healthy children

    PubMed Central

    Pacheco, Maria Christina Thomé; Fiorott, Bruna Santos; Finck, Nathalia Silveira; de Araújo, Maria Teresa Martins

    2015-01-01

    INTRODUCTION: The main cause of mouth breathing and sleep-disordered breathing (SDB) in childhood is associated with upper airway narrowing to varying degrees. OBJECTIVE: The aim of this study was to assess the prevalence of morphological and functional craniofacial changes and the main clinical symptoms of SDB in healthy children. METHODS: A cross-sectional observational study was conducted. A sample comprising 687 healthy schoolchildren, aged 7-12 years old and attending public schools, was assessed by medical history, clinical medical and dental examination, and respiratory tests. The self-perceived quality of life of mouth breathing children was obtained by a validated questionnaire. RESULTS: Out of the total sample, 520 children were nose breathers (NB) while 167 (24.3%) were mouth breathers (MB); 32.5% had severe hypertrophy of the palatine tonsils, 18% had a Mallampati score of III or IV, 26.1% had excessive overjet and 17.7% had anterior open bite malocclusion. Among the MB, 53.9% had atresic palate, 35.9% had lip incompetence, 33.5% reported sleepiness during the day, 32.2% often sneezed, 32.2% had a stuffy nose, 19.6% snored, and 9.4% reported having the feeling to stop breathing while asleep. However, the self-perception of their quality of life was considered good. CONCLUSION: High prevalence of facial changes as well as signs and symptoms of mouth breathing were found among health children, requiring early diagnosis and treatment to reduce the risk of SDB. PMID:26154460

  16. [Craniofacial neuralgias].

    PubMed

    Mikula, Ivan

    2008-05-01

    Craniofacial neuralgias are characterized by sudden paroxysmal pain along the distribution of one or more of the cranial or upper cervical spinal nerves. The most significant neuralgia of the craniofacial region is trigeminal neuralgia, while geniculate neuralgia, glossopharyngeal neuralgia and occipital neuralgia are less common. Trigeminal neuralgia may be primary or secondary. Idiopathic trigeminal neuralgia or tic douloureux has been recognized for centuries as an extremely painful disorder most commonly involving the maxillary nerve. Recurrent lancinating, shocklike unilateral pain lasting for seconds to minutes is provoked by non noxious stimulation of the skin at specific sites around the face and less frequently by movement of the tongue. The trigger zones are usually within the same dermatome as the painful sensation. After each episode, there is usually a refractive period during which stimulation of the trigger zone will not induce pain. Idiopathic trigeminal neuralgia occurs somewhat more frequently in women and usually begins in individuals 50 to 70 years of age. There is no pain between attacks, and the frequency of painful episodes can range from several per day to only a few per year. With time, the features may become more atypical, with greater areas of more enduring and dull pain and occasionally bilateral pain, rarely on both sides simultaneously. No sensory or reflex deficit is detectable by routine neurologic testing. Diagnostic local anesthetic blocks will identify the specific nerves involved and the trigger point distribution. Neurologic and neuroradiologic examination is advised in all cases to rule out diseases such as intracranical tumors, vascular malformations or multiple sclerosis.

  17. Effect of bite force and diet composition on craniofacial diversification of Southern South American human populations.

    PubMed

    Menéndez, Lumila; Bernal, Valeria; Novellino, Paula; Perez, S Ivan

    2014-09-01

    Ecological factors can be important to shape the patterns of morphological variation among human populations. Particularly, diet plays a fundamental role in craniofacial variation due to both the effect of the nutritional status-mostly dependent on the type and amount of nutrients consumed-on skeletal growth and the localized effects of masticatory forces. We examine these two dimensions of diet and evaluate their influence on morphological diversification of human populations from southern South America during the late Holocene. Cranial morphology was measured as 3D coordinates defining the face, base and vault. Size, form, and shape variables were obtained for 474 adult individuals coming from 12 samples. Diet composition was inferred from carious lesions and δ(13) C data, whereas bite forces were estimated using traits of main jaw muscles. The spatial structure of the morphological and ecological variables was measured using correlograms. The influence of diet composition and bite force on morphometric variation was estimated by a spatial regression model. Cranial variation and diet composition display a geographical structure, while no geographical pattern was observed in bite forces. Cranial variation in size and form is significantly associated with diet composition, suggesting a strong effect of systemic factors on cranial growth. Conversely, bite forces do not contribute significantly to the pattern of morphological variation among the samples analyzed. Overall, these results show that an association between diet composition and hardness cannot be assumed, and highlight the complex relationship between morphological diversification and diet in human populations. Copyright © 2014 Wiley Periodicals, Inc.

  18. Bone modeling patterns and morphometric craniofacial variation in individuals from two prehistoric human populations from Argentina.

    PubMed

    Brachetta Aporta, Natalia; Martinez-Maza, Cayetana; Gonzalez, Paula N; Bernal, Valeria

    2014-10-01

    Native human populations from South America display high levels of craniofacial variation encompassing gracile and robust skulls. Nevertheless, the processes of bone modeling by which morphological variation among populations were attained, remain poorly understood. Here we analyze the relationship between patterns of bone formation and resorption and morphometric variation in the upper face of adults belonging to farmers and hunter-gatherers from northwestern and south Argentina. Our analyses reveal a common pattern of bone modeling of the malar bone characterized by the presence of formation areas. Thus, the larger size and greater development of malar bone exhibited by hunter-gatherers would be linked to a greater magnitude of bone formation activity. Conversely, the glabella and the superciliary arch presented both formation and resorption areas with a variable distribution among individuals. In the extreme corresponding to more robust morphologies, the great development of the glabella is related to the presence of large formation fields, both in the upper region and toward the frontonasal suture. The less robust morphologies show resorption fields at the upper margin of the glabella, which would contribute to the weaker development of this region. The superciliary arch showed a complex relationship between its morphometric and histological variation; the individuals located at both extremes of the shape space presented large resorption areas located on its upper margin. Overall, our results show the existence of intraspecific variation in the patterns of bone modeling in the human upper face. © 2014 Wiley Periodicals, Inc.

  19. Craniofacial Microsomia

    PubMed Central

    Birgfeld, Craig B.; Heike, Carrie

    2012-01-01

    Craniofacial microsomia (CFM) is one of the most common congenital conditions treated in craniofacial centers worldwide. This condition is variably associated with anomalies of the jaws, ears, facial soft tissue, orbits, and facial nerve function and can be associated with extracranial anomalies. The cause of this condition is unknown, though CFM has been associated withprenatalexposures and genetic abnormalities. Diagnosis, treatment, and outcome assessment in CFM is challenging due to the wide phenotypic spectrum observed in this condition. Surgical treatment requires a coordinated team approach involving multiple specialties, which can include plastic surgery, craniofacial surgery, orthognathic surgery, and microsurgery. A wide variety of surgical options exist, and individual treatment plans should be based on the patient's needs. Although CFM can be challenging to treat, successful outcomes are rewarding. We provide a review of the common craniofacial surgical treatments for individuals with CFM. PMID:23633936

  20. 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.

  1. Selective brain cooling seems to be a mechanism leading to human craniofacial diversity observed in different geographical regions.

    PubMed

    Irmak, M K; Korkmaz, A; Erogul, O

    2004-01-01

    Selective brain cooling (SBC) can occur in hyperthermic humans despite the fact that humans have no carotid rete, a vascular structure that facilitates countercurrent heat exchange located at the base of the skull in some mammals. Emissary and angular veins, upper respiratory tract, tympanic cavity and cerebrospinal fluid are major components of SBC system in humans. The efficiency of SBC is increased by evaporation of sweat on the head and by ventilation through the nose, but it is surprising to find out that mammals do not display SBC during exercise hyperthermia. What is the explanation then for the SBC at high body temperatures? Our hypothesis is that selective brain cooling protects the brain from thermal damage in a long-standing manner by allowing adaptive mechanisms to change the craniofacial morphology appropriate for different environmental conditions. Since the brain can only be as big that can cool, it is not surprising to find a lower (below 1300 cm(3)) cranial volume in Australian Aborigines with respect to the one (over 1450 cm(3)) in Eskimos. In addition to lower brain volume, other craniofacial features such as thick everted lips, broader nasal cavity and bigger paranasal sinuses that provide more evaporating surfaces seem to be anatomical variations developed in time for an effective SBC in hot climates. It was reported previously that these biological adaptations result from the tissues of neural crest origin. Among the crest derivatives, leptomeninges (pia and arachnoid mater), skeletal and connective tissues of the face and much of the skull seem to be structures upon which environment operates to produce more convenient craniofacial morphology for an effective SBC. In conclusion, selective brain cooling seems to be a mechanism leading to adaptive craniofacial diversity observed in different geographical regions. Thus, SBC is necessary for long-term biological adaptation, not for protecting the brain from acute thermal damage.

  2. Less known non-infectious and neuromusculoskeletal system-originated anterolateral neck and craniofacial pain disorders.

    PubMed

    Aydil, Utku; Kizil, Yusuf; Köybaşioğlu, Ahmet

    2012-01-01

    Pain syndromes of neuromusculoskeletal origin are not well-known by most of the clinicians working on head and neck area. As a result, most of the patients with these syndromes are either overlooked without having any treatment or they inappropriately have antibiotic treatments or surgical interventions such as dental extractions and tonsillectomies. Better recognition of the pain syndromes of the neck and face region or entities related to neuromusculoskeletal system may result in more appropriate and effective management of such conditions while avoiding unnecessary medical and surgical treatments. In this review, causes, clinical characteristics, diagnostic and treatment modalities of relatively less known craniofacial and neck pain entities including Eagle syndrome, carotidynia, glossopharyngeal neuralgia, superior laryngeal neuralgia, hyoid bone syndrome, acute calcific retropharyngeal tendinitis, temporal tendinitis, thyroid and cricoid cartilage syndromes, and mastoid process syndrome are summarized.

  3. Craniofacial morphogenesis workshop report.

    PubMed

    Solursh, M; Murray, J

    1994-05-01

    The following report highlights the discussions and interaction at the workshop on craniofacial morphogenesis, sponsored by The Human Frontier Science Program, held in April 1993 at the University of Iowa. A brief summary of selected sessions is included to exemplify the benefits of bringing together individuals from various disciplines and backgrounds in order to establish a unified theory of craniofacial morphogenesis. The synthesis of information and experience of a wide range of approaches made the 4-day period an invaluable experience for the participants from nine different countries.

  4. Translational genetics: advancing fronts for craniofacial health.

    PubMed

    D'Souza, R N; Dunnwald, M; Dunnvald, M; Frazier-Bowers, S; Polverini, P J; Wright, J T; de Rouen, T; Vieira, A R

    2013-12-01

    Scientific opportunities have never been better than today! The completion of the Human Genome project has sparked hope and optimism that cures for debilitating conditions can be achieved and tailored to individuals and communities. The availability of reference genome sequences and genetic variations as well as more precise correlations between genotype and phenotype have facilitated the progress made in finding solutions to clinical problems. While certain craniofacial and oral diseases previously deemed too difficult to tackle have benefited from basic science and technological advances over the past decade, there remains a critical need to translate the fruits of several decades' worth of basic and clinical research into tangible therapies that can benefit patients. The fifth Annual Fall Focused Symposium, "Translational Genetics - Advancing Fronts for Craniofacial Health", was created by the American Association for Dental Research (AADR) to foster its mission to advance interdisciplinary research that is directed toward improving oral health. The symposium showcased progress made in identifying molecular targets that are potential therapeutics for common and rare dental diseases and craniofacial disorders. Speakers focused on translational and clinical applications of their research and, where applicable, on strategies for new technologies and therapeutics. The critical needs to transfer new knowledge to the classroom and for further investment in the field were also emphasized. The symposium underscored the importance of basic research, chairside clinical observations, and population-based studies in driving the new translational connections needed for the development of cures for the most common and devastating diseases involving the craniofacial complex.

  5. Old World sources of the first New World human inhabitants: A comparative craniofacial view

    PubMed Central

    Brace, C. Loring; Nelson, A. Russell; Seguchi, Noriko; Oe, Hiroaki; Sering, Leslie; Qifeng, Pan; Yongyi, Li; Tumen, Dashtseveg

    2001-01-01

    Human craniofacial data were used to assess the similarities and differences between recent and prehistoric Old World samples, and between these samples and a similar representation of samples from the New World. The data were analyzed by the neighbor-joining clustering procedure, assisted by bootstrapping and by canonical discriminant analysis score plots. The first entrants to the Western Hemisphere of maybe 15,000 years ago gave rise to the continuing native inhabitants south of the U.S.–Canadian border. These show no close association with any known mainland Asian population. Instead they show ties to the Ainu of Hokkaido and their Jomon predecessors in prehistoric Japan and to the Polynesians of remote Oceania. All of these also have ties to the Pleistocene and recent inhabitants of Europe and may represent an extension from a Late Pleistocene continuum of people across the northern fringe of the Old World. With roots in both the northwest and the northeast, these people can be described as Eurasian. The route of entry to the New World was at the northwestern edge. In contrast, the Inuit (Eskimo), the Aleut, and the Na-Dene speakers who had penetrated as far as the American Southwest within the last 1,000 years show more similarities to the mainland populations of East Asia. Although both the earlier and later arrivals in the New World show a mixture of traits characteristic of the northern edge of Old World occupation and the Chinese core of mainland Asia, the proportion of the latter is greater for the more recent entrants. PMID:11481450

  6. [Craniofacial fractures].

    PubMed

    Benech, A; Gerbino, G

    1990-12-01

    Results of early combined maxillo-facial and neurosurgical treatment of 53 craniofacial fractures are referred. The fracture location was in 31 cases central midfrontal, 10 lateral supraorbital and 12 combined central and lateral fractures. 35 fractures interested the floor and the posterior wall of frontal sinus, lacerating the underlying dura and cortical tissue. In 19 fractures orbital displacement was present. The key points in the management of these patients are: 1) Early (within 1 to 5 days) and one stage neurosurgical-maxillofacial procedure. Immediate intervention is indicated only in case of evolutive neurological lesions; 2) wide exposition of all the injuries through bicoronal incision and bone flap; 3) assessment of fractures pattern and amount of bone loss; 4) reconstruction of craniofacial frame with osteosynthesis and autologous bone grafts (35 cases iliac crest, 7 split calvarial graft); 5) interosseous wiring is used in sutured mosaic, small bone fragments and intraoperative temporary fixation; miniplates are used for rigid fixation of craniofacial pillars; 6) for optimal cosmetic result reconstruction of supraorbital ridge, nasoglabellar region and zygomatic arch is essential; 7) fractures involving the sinus floor, posterior wall and the nasofrontal duct result in direct communication between the nose and intracranial cavity with high risk of infection and mucocele formation. Cranialization of the sinus removing the posterior wall and all the mucosa is mandatory. The nasofrontal duct, the floor and sinus dead space are obliterated with autologous bone chips. Osteoneogenesis occurred in all the cases.

  7. 77 FR 40369 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

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  8. 75 FR 39547 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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    2010-07-09

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  9. 78 FR 56902 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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    2013-09-16

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  11. 77 FR 59202 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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  13. 76 FR 22111 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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  9. Craniofacial muscle pain: review of mechanisms and clinical manifestations.

    PubMed

    Svensson, P; Graven-Nielsen, T

    2001-01-01

    Epidemiologic surveys of temporomandibular disorders (TMD) have demonstrated that a considerable proportion of the population--up to 5% or 6%--will experience persistent pain severe enough to seek treatment. Unfortunately, the current diagnostic classification of craniofacial muscle pain is based on descriptions of signs and symptoms rather than on knowledge of pain mechanisms. Furthermore, the pathophysiology and etiology of craniofacial muscle pain are not known in sufficient detail to allow causal treatment. Many hypotheses have been proposed to explain cause-effect relationships; however, it is still uncertain what may be the cause of muscle pain and what is the effect of muscle pain. This article reviews the literature in which craniofacial muscle pain has been induced by experimental techniques in animals and human volunteers and in which the effects on somatosensory and motor function have been assessed under standardized conditions. This information is compared to the clinical correlates, which can be derived from the numerous cross-sectional studies in patients with craniofacial muscle pain. The experimental literature clearly indicates that muscle pain has significant effects on both somatosensory and craniofacial motor function. Typical somatosensory manifestations of experimental muscle pain are referred pain and increased sensitivity of homotopic areas. The craniofacial motor function is inhibited mainly during experimental muscle pain, but phase-dependent excitation is also found during mastication to reduce the amplitude and velocity of jaw movements. The underlying neurobiologic mechanisms probably involve varying combinations of sensitization of peripheral afferents, hyperexcitability of central neurons, and imbalance in descending pain modulatory systems. Reflex circuits in the brain stem seem important for the adjustment of sensorimotor function in the presence of craniofacial pain. Changes in somatosensory and motor function may therefore be

  10. Geometric morphometric analysis of craniofacial variation, ontogeny and modularity in a cross-sectional sample of modern humans

    PubMed Central

    Wellens, H L L; Kuijpers-Jagtman, A M; Halazonetis, D J

    2013-01-01

    This investigation aimed to quantify craniofacial variation in a sample of modern humans. In all, 187 consecutive orthodontic patients were collected, of which 79 were male (mean age 13.3, SD 3.7, range 7.5–40.8) and 99 were female (mean age 12.3, SD 1.9, range 8.7–19.1). The male and female subgroups were tested for differences in mean shapes and ontogenetic trajectories, and shape variability was characterized using principal component analysis. The hypothesis of modularity was tested for six different modularity scenarios. The results showed that there were subtle but significant differences in the male and female Procrustes mean shapes. Males were significantly larger. Mild sexual ontogenetic allometric divergence was noted. Principal component analysis indicated that, of the four retained biologically interpretable components, the two most important sources of variability were (i) vertical shape variation (i.e. dolichofacial vs. brachyfacial growth patterns) and (ii) sagittal relationships (maxillary prognatism vs. mandibular retrognathism, and vice versa). The mandible and maxilla were found to constitute one module, independent of the skull base. Additionally, we were able to confirm the presence of an anterior and posterior craniofacial columnar module, separated by the pterygomaxillary plane, as proposed by Enlow. These modules can be further subdivided into four sub-modules, involving the posterior skull base, the ethmomaxillary complex, a pharyngeal module, and the anterior part of the jaws. PMID:23425043

  11. The correlation between craniofacial morphology and sleep-disordered breathing in children in an undergraduate orthodontic clinic.

    PubMed

    Tsuda, Hiroko; Fastlicht, Sandra; Almeida, Fernanda R; Lowe, Alan A

    2011-05-01

    The aim of this study was to assess children in an orthodontic teaching clinic to determine the relationship between sleep-disordered breathing (SDB) symptoms and craniofacial morphology. All parents were asked to complete a SDB questionnaire at the commencement of orthodontic therapy. A cephalometric analysis included face heights, hyoid position, soft palate lengths, mandibular, vertical airway, overjet, and overbite. Study model measurements included dental width, depth, and palatal height. The subjects were divided into two groups according to their dentition stage: early or late mixed. Data from 173 children (male 50.3%, mean age 10.1 ± 1.7 years) that completed the OSA-18 questionnaire and the cephalometric (CA) and model (MA) analyses were evaluated. The questionnaire suggested that only two children in the orthodontic pool had an increased chance of exhibiting SDB. However, loud snoring, mouth breathing, and difficulty awakening were reported in more than 20% of the children. Overall, a higher total score correlated with retroclined upper incisors (CA) and high palatal height (MA, p < 0.05). Although there was no significant score differences between the groups, a higher total score correlated with a long soft palate (CA, p < 0.05) in the early mixed dentition group and a high palatal height (MA) in the late mixed dentition group (p < 0.05). Even though few patients were suspected as having SDB, symptoms were related to many cephalometric variables and study model measurements. Since the etiology of SDB is believed to involve multiple factors, such patients may exhibit some risk of developing SDB in the future.

  12. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  13. Diffuse noxious inhibitory control evoked by tonic craniofacial pain in humans.

    PubMed

    Sowman, P F; Wang, K; Svensson, P; Arendt-Nielsen, L

    2011-02-01

    Tonic pain in one body segment can inhibit the perception of pain in another body segment. This phenomenon is mediated by diffuse noxious inhibitory controls (DNIC), and its efficacy in craniofacial regions is investigated in this study. A compressive device that evoked a tonic, moderate/severe, headache-like, conditioning pain (∼8/10 on a visual analogue scale) was applied for 15min. Eleven males participated in the study. Pressure pain threshold (PPT) and pressure pain tolerance (PPTol) at multiple heterosegmental body sites (right masseter, splenius capitis, second intermediate phalange, brachioradialis and tibialis anterior) were measured before, during and at multiple time points (5, 20 and 35min) after the termination of the conditioning pain. PPTs and PPTols were compared within participants across two experimental sessions; one that included painful conditioning stimulation, and a separate control session on a different day. Painful conditioning increased PPT significantly during pain over the masseter (p<0.05) and over the tibialis anterior (p<0.01). PPTol was unchanged. In the period after the painful conditioning stimulation PPT was depressed compared to control. This study shows that pain evoked from the craniofacial region evokes DNIC-like mechanisms on segmental as well as heterosegmental sites.

  14. Monogenic human skin disorders.

    PubMed

    Lemke, Johannes R; Kernland-Lang, Kristin; Hörtnagel, Konstanze; Itin, Peter

    2014-01-01

    Human genodermatoses represent a broad and partly confusing spectrum of countless rare diseases with confluent and overlapping phenotypes often impeding a precise diagnosis in an affected individual. High-throughput sequencing techniques have expedited the identification of novel genes and have dramatically simplified the establishment of genetic diagnoses in such heterogeneous disorders. The precise genetic diagnosis of a skin disorder is crucial for the appropriate counselling of patients and their relatives regarding the course of the disease, prognosis and recurrence risks. Understanding the underlying pathophysiology is a prerequisite to understanding the disease and developing specific, targeted or individualized therapeutic approaches. We aimed to create a comprehensive overview of human genodermatoses and their respective genetic aetiology known to date. We hope this may represent a useful tool in guiding dermatologists towards genetic diagnoses, providing patients with individual knowledge on the respective disorder and applying novel research findings to clinical practice.

  15. Craniofacial Resection

    PubMed Central

    Ross, Donald A.; Marentette, Lawrence J.; Moore, Charles E.; Switz, Kristin L.

    1999-01-01

    The authors have successfully utilized a modified subcranial approach to the anterior skull base, based upon the procedure first described by Joram Raveh, as an alternative to standard craniofacial resection. The complication rate of this procedure in 31 consecutive cases (28 tumors, 2 congenital malformations, and 1 mucocele) has been 19.4% with no permanent complications, no deaths, no new neurological deficits, no brain injuries, no infections, and no seizures. Minor complications without permanent sequelae included two cases of tension pnenmocephalus, a subdural hygroma, two transient cerebrospinal fluid leaks, and a case of bacterial meningitis secondary to fecal contamination of a lumbar drain in a child. Average length of hospitalization was 7.1 days (range 2 to 16 days). The overall complication rate is considerably below the complication rate for other reported craniofacial procedures. We describe the technique we have used and the results. The subcranial approach as described herein provides wide exposure of the anterior cranial base without brain retraction, does not require prolonged operating times or hospitalization, and has a potentially lower complication rate than reported for other transfrontal transbasal approaches. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:17171124

  16. Human HOX gene disorders.

    PubMed

    Quinonez, Shane C; Innis, Jeffrey W

    2014-01-01

    The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These processes range from a central role in anterior-posterior patterning of the developing embryo to roles in oncogenesis that are yet to be fully elucidated. In vertebrates there are a total of 39 Hox genes divided into 4 separate clusters. Of these, mutations in 10 Hox genes have been found to cause human disorders with significant variation in their inheritance patterns, penetrance, expressivity and mechanism of pathogenesis. This review aims to describe the various phenotypes caused by germline mutation in these 10 Hox genes that cause a human phenotype, with specific emphasis paid to the genotypic and phenotypic differences between allelic disorders. As clinical whole exome and genome sequencing is increasingly utilized in the future, we predict that additional Hox gene mutations will likely be identified to cause distinct human phenotypes. As the known human phenotypes closely resemble gene-specific murine models, we also review the homozygous loss-of-function mouse phenotypes for the 29 Hox genes without a known human disease. This review will aid clinicians in identifying and caring for patients affected with a known Hox gene disorder and help recognize the potential for novel mutations in patients with phenotypes informed by mouse knockout studies.

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

    PubMed Central

    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.

    2014-01-01

    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. PMID:25281006

  18. Gene Therapy: Implications for Craniofacial Regeneration

    PubMed Central

    Scheller, Erica L.; Villa-Diaz, Luis G; Krebsbach, Paul H.

    2011-01-01

    Gene therapy in the craniofacial region provides a unique tool for delivery of DNA to coordinate protein production in both time and space. The drive to bring this technology to the clinic is derived from the fact that over 85% of the global population may at one time require repair or replacement of a craniofacial structure. This need ranges from mild tooth decay and tooth loss to temporomandibular joint disorders and large-scale reconstructive surgery. Our ability to insert foreign DNA into a host cell has been developing since early uses of gene therapy to alter bacterial properties for waste cleanup in the 1980s followed by successful human clinical trials in the 1990s to treat severe combined immunodeficiency. In the past twenty years the emerging field of craniofacial tissue engineering has adopted these techniques to enhance regeneration of mineralized tissues, salivary gland, periodontium, and to reduce tumor burden of head and neck squamous cell carcinoma. Studies are currently pursuing research on both biomaterial-mediated gene delivery as well as more clinically efficacious, though potentially more hazardous, viral methods. Though hundreds of gene therapy clinical trials have taken place in the past twenty years, we must still work to ensure an ideal safety profile for each gene and delivery method combination. With adequate genotoxicity testing, we can expect gene therapy to augment protein delivery strategies and potentially allow for tissue-specific targeting, delivery of multiple signals, and increased spatial and temporal control with the goal of natural tissue replacement in the craniofacial complex. PMID:22337437

  19. [Craniofacial fibrous dysplasia].

    PubMed

    Couturier, A; Aumaître, O; Mom, T; Gilain, L; André, M

    2016-12-01

    Fibrous dysplasia of bone is a benign, uncommon, sporadic, congenital skeletal disorder resulting in deformity. This disease arises from activating somatic mutation in GNAS which encodes the α subunit of the G stimulatory protein associated with proliferation of undifferentiated osteogenic cells resulting in marrow fibrosis, abnormal matrix production, and stimulation of osteoclastic resorption upon overproduction of IL-6 observed in dysplastic cells. Fibrous dysplasia may be monostotic or polyostotic. This mutation affecting many tissues, café au lait skin macules and endocrinopathies (precocious puberty, hyperthyroidism, growth hormone excess, Cushing syndrome) may be associated in McCune-Albright syndrome, but also myxoma in Mazabraud syndrome or phosphate diabetes. Diagnosis of craniofacial fibrous dysplasia should be considered in the presence of headache, neuralgia, sensory disorders (vision, hearing, balance, smelling), functional disorders (nasal obstruction, nasolacrimal duct obstruction, non-matching occlusion), infectious complications (sinusitis, otitis, mastoiditis). Such symptoms should lead to perform craniofacial CT scan completed with MRI. Bone biopsy is not systematic. Surgical treatment is discussed in cases of nervous complication, facial deformity or active lesions. In case of pain resistant to conventional analgesics, intravenous bisphosphonates can be proposed. In non-responder patients, several case reports suggest the efficacy of a monoclonal antibody directed against the IL-6 receptor which requires to be confirmed by randomized studies.

  20. Imaging of craniofacial fibrous dysplasia.

    PubMed

    Lisle, D A; Monsour, P A J; Maskiell, C D

    2008-08-01

    Fibrous dysplasia is a relatively common disorder of bone. It may affect the bones of the face and skull and, in so doing, produce a wide variety of clinical presentations. Plain film assessment of craniofacial fibrous dysplasia may be difficult because of varying appearances and complex, overlapping structures. The MRI appearances of fibrous dysplasia are often non-specific and may be confusing. Findings on CT are also variable, but more commonly lead to a specific diagnosis. This is because of the characteristic ground-glass appearance of woven bone, seen on CT in most if not all cases of craniofacial fibrous dysplasia.

  1. 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.

  2. Children's Craniofacial Association

    MedlinePlus

    ... and families affected by facial differences. Children's Craniofacial Association is a national, 501(c)3 nonprofit organization, ... contactCCA@ccakids.com Copyright © 2011-17 Children's Craniofacial Association. All Rights Reserved. Internet Marketing by Socius Marketing ...

  3. [Basic disorders in human communication].

    PubMed

    Peñaloza-López, Y; Gutiérrez-Silva, J; Andrade-Illañez, E N; Fierro-Evans, M A; Hernández-López, X

    1989-01-01

    This paper specifies the areas and disorders that concern human communication medicine. The frequency of the diverse disorders is analyzed in relation to age and sex, and the distribution in group ages of several disabling diseases is also discussed.

  4. A noncoding expansion in EIF4A3 causes Richieri-Costa-Pereira syndrome, a craniofacial disorder associated with limb defects.

    PubMed

    Favaro, Francine P; Alvizi, Lucas; Zechi-Ceide, Roseli M; Bertola, Debora; Felix, Temis M; de Souza, Josiane; Raskin, Salmo; Twigg, Stephen R F; Weiner, Andrea M J; Armas, Pablo; Margarit, Ezequiel; Calcaterra, Nora B; Andersen, Gregers R; McGowan, Simon J; Wilkie, Andrew O M; Richieri-Costa, Antonio; de Almeida, Maria L G; Passos-Bueno, Maria Rita

    2014-01-02

    Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5' untranslated region (5' UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  5. New insights into craniofacial malformations

    PubMed Central

    Twigg, Stephen R.F.; Wilkie, Andrew O.M.

    2015-01-01

    Development of the human skull and face is a highly orchestrated and complex three-dimensional morphogenetic process, involving hundreds of genes controlling the coordinated patterning, proliferation and differentiation of tissues having multiple embryological origins. Craniofacial malformations that occur because of abnormal development (including cleft lip and/or palate, craniosynostosis and facial dysostoses), comprise over one-third of all congenital birth defects. High-throughput sequencing has recently led to the identification of many new causative disease genes and functional studies have clarified their mechanisms of action. We present recent findings in craniofacial genetics and discuss how this information together with developmental studies in animal models is helping to increase understanding of normal craniofacial development. PMID:26085576

  6. New developments in craniofacial surgery research.

    PubMed

    Mehrara, B J; Longaker, M T

    1999-09-01

    The recent explosion in our understanding of developmental biology and genetics has enhanced our understanding of craniofacial biology. While it is not possible to summarize all new developments in craniofacial research, this article will review three areas: fetal models and surgery for craniofacial disorders, the biology of distraction osteogenesis, and the molecular mechanisms of cranial suture fusion. Numerous models of craniofacial disorders have been described, including small, short gestation and large, long gestation. The benefits and shortcomings of each are discussed. In addition, we discuss recent studies investigating the molecular mechanisms of mandibular distraction osteogenesis. Finally, we present a review of recent advances in the understanding of mechanisms of craniosynostosis, with particular emphasis on the biology of programmed cranial suture fusion in rodents.

  7. 4D-computerized visualisation of human craniofacial skeletal growth and of the development of the dentition.

    PubMed

    Radlanski, R J; van der Linden, F P; Ohnesorge, I

    1999-01-01

    The understanding of growth and developmental changes can be improved when shapes and changes in size, proportion, and relationships are visualized in 3 dimensions and at different stages. This applies particularly to craniofacial skeletal growth and the development of the dentition. For that purpose 3D-data were collected from prenatal human heads ranging from 18 up to 275 mm CRL and from a collection of macerated fetal and postnatal skulls. Computer-aided graphical reconstructions were obtained from histological serial sections of embryonic and early fetal specimens. Proportional changes in the growing skull were recorded by means of radiological and cephalometric evaluation. In addition, computed tomography was applied to fetal and postnatal skulls. Furthermore, the prenatal and postnatal development of the dentition was digitized. To that end 3D-polygone sets of these data were read into a workstation computer and animated by means of the software Soft Image (Microsoft). This comprehensive 4D insight into growth facilitates the understanding and teaching of normal and abnormal development.

  8. 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.

  9. 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

  10. Head development. Craniofacial genetics makes headway.

    PubMed

    Richman, J M

    1995-04-01

    Studies of neural crest migration in animal models, and of human syndromes in which craniofacial development is abnormal, are helping us to understand both prenatal and postnatal development of the head.

  11. An Immunohistochemical Study of Matrix Proteins in the Craniofacial Cartilage in Midterm Human Fetuses

    PubMed Central

    Shibata, S.; Sakamoto, Y.; Baba, O.; Qin, C.; Murakami, G.; Cho, B.H.

    2013-01-01

    Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel’s cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel’s cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes. PMID:24441192

  12. An immunohistochemical study of matrix proteins in the craniofacial cartilage in midterm human fetuses.

    PubMed

    Shibata, S; Sakamoto, Y; Baba, O; Qin, C; Murakami, G; Cho, B H

    2013-12-02

    Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel's cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel's cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes.

  13. Disorder in Complex Human System

    NASA Astrophysics Data System (ADS)

    Akdeniz, K. Gediz

    2011-11-01

    Since the world of human and whose life becomes more and more complex every day because of the digital technology and under the storm of knowledge (media, internet, governmental and non-governmental organizations, etc...) the simulation is rapidly growing in the social systems and in human behaviors. The formation of the body and mutual interactions are left to digital technological, communication mechanisms and coding the techno genetics of the body. Deconstruction begins everywhere. The linear simulation mechanism with modern realities are replaced by the disorder simulation of human behaviors with awareness realities. In this paper I would like to introduce simulation theory of "Disorder Sensitive Human Behaviors". I recently proposed this theory to critique the role of disorder human behaviors in social systems. In this theory the principle of realty is the chaotic awareness of the complexity of human systems inside of principle of modern thinking in Baudrillard's simulation theory. Proper examples will be also considered to investigate the theory.

  14. A systematic review of the oral and craniofacial manifestations of cri du chat syndrome.

    PubMed

    Corcuera-Flores, José-Ramón; Casttellanos-Cosano, Lizett; Torres-Lagares, Daniel; Serrera-Figallo, María Ángeles; Rodríguez-Caballero, Ángela; Machuca-Portillo, Guillermo

    2016-07-01

    Cri du chat syndrome is an autosomal disorder. Because it affects few people in the population it is considered a rare disease, yet it is one of the most common autosomal chromosomal syndromes in humans. It entails pathognomonic alterations that affect the craniofacial and oral anatomy of patients. The aim of this study is to review these craniofacial and oral abnormalities in patients with Cri du chat syndrome. The PubMed Medline database was searched using two different strategies. First, we used "Dentistry" and "Cri du chat" as keywords; second, we used "Cri du chat" and "craniofacial." Seven articles in which the main orofacial and cranio-skeletal characteristics of patients with Cri du chat syndrome were described were selected according to the inclusion and exclusion criteria. Cri du Chat syndrome entails pathognomonic characteristics in the craniofacial area (epicanthus, short philtrum, and wide nasal bridge), the oral area (mandibular retrognathism and anterior open bite) and the cranial region (alterations at the cranial base angle and a small upper airway). However, more studies on larger samples are needed to specify the orofacial and craniofacial characteristics of patients with Cri du chat syndrome more accurately. Clin. Anat. 29:555-560, 2016. © 2015 Wiley Periodicals, Inc.

  15. The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in Xenopus

    PubMed Central

    Griffin, John N.; Sondalle, Samuel B.; del Viso, Florencia; Baserga, Susan J.; Khokha, Mustafa K.

    2015-01-01

    The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC) of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival. PMID:25756904

  16. The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus.

    PubMed

    Griffin, John N; Sondalle, Samuel B; Del Viso, Florencia; Baserga, Susan J; Khokha, Mustafa K

    2015-03-01

    The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC) of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival.

  17. 76 FR 78013 - National Institute of Dental and Craniofacial Research; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-15

    ... HUMAN SERVICES National Institutes of Health National Institute of Dental and Craniofacial Research... commercial property such as patentable material, and personal information concerning individuals associated... personal privacy. Name of Committee: National Institute of Dental and Craniofacial Research Special...

  18. 75 FR 7485 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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    2010-02-19

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  19. 77 FR 10540 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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  1. 77 FR 8268 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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    2012-02-14

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  5. 76 FR 58284 - National Institute of Dental and Craniofacial Research; Notice of Closed Meetings

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  7. 75 FR 52537 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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  9. 77 FR 76297 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

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  10. 76 FR 5183 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

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  11. 75 FR 8976 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

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  12. 78 FR 3009 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-15

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  13. De Novo Duplication of 7p21.1p22.2 in a Child with Autism Spectrum Disorder and Craniofacial Dysmorphism.

    PubMed

    Udayakumar, Achandira M; Al-Mamari, Watfa; Al-Sayegh, Abeer; Al-Kindy, Adila

    2015-08-01

    The duplication of the short arm of chromosome 7 as de novo is extremely rare. The phenotype spectrum varies depending on the region of duplication. We report a case of de novo duplication of chromosomal region 7p21.1p22.2 in a three-year-old male child with autism who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in January 2012. The patient was diagnosed with craniofacial dysmorphism, global developmental delay, hypotonia and bilateral cryptorchidism. The duplication was detected by conventional G-banded karyotype analysis/fluorescence in situ hybridisation and confirmed by array comparative genomic hybridisation. To the best of the authors' knowledge, this is the first report of chromosomal region 7p21.1 involvement in an autistic patient showing features of a 7p duplication phenotype. Identifying genes in the duplicated region using molecular techniques is recommended to promote characterisation of the phenotype and associated condition. It may also reveal the possible role of these genes in autism spectrum disorder.

  14. Effect of sex-hormone levels, sex, body mass index and other host factors on human craniofacial bone regeneration with bioactive tricalcium phosphate grafts.

    PubMed

    Knabe, Christine; Mele, Aynur; Kann, Peter Herbert; Peleska, Barbara; Adel-Khattab, Doaa; Renz, Harald; Reuss, Alexander; Bohner, Marc; Stiller, Michael

    2017-04-01

    Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p < 0.05). Histomorphometry revealed trends toward greater bone formation and osteogenic marker expression with non-smokers compared to smokers. In male patients, higher E2 levels and higher BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Relationships between craniofacial pain and bruxism.

    PubMed

    Svensson, P; Jadidi, F; Arima, T; Baad-Hansen, L; Sessle, B J

    2008-07-01

    A still commonly held view in the literature and clinical practice is that bruxism causes pain because of overloading of the musculoskeletal tissue and craniofacial pain, on the other hand, triggers more bruxism. Furthermore, it is often believed that there is a dose-response gradient so that more bruxism (intensity, duration) leads to more overloading and pain. Provided the existence of efficient techniques to treat bruxism, it would be straightforward in such a simple system to target bruxism as the cause of pain and hence treat the pain. Of course, human biological systems are much more complex and therefore, it is no surprise that the relationship between bruxism and pain is far from being simple or even linear. Indeed, there are unexpected relationships, which complicate the establishment of adequate explanatory models. Part of the reason is the complexity of the bruxism in itself, which presents significant challenges related to operationalized criteria and diagnostic tools and underlying pathophysiology issues, which have been dealt with in other reviews in this issue. However, another important reason is the multifaceted nature of craniofacial pain. This review will address our current understanding of classification issues, epidemiology and neurobiological mechanisms of craniofacial pain. Experimental models of bruxism may help to further the understanding of the relationship between craniofacial pain and bruxism in addition to insights from intervention studies. The review will enable clinicians to understand the reasons why simple cause-effect relationships between bruxism and craniofacial pain are inadequate and the current implications for management of craniofacial pain.

  16. [Current gene study in etiological analysis of congenital craniofacial abnormalities].

    PubMed

    Feng, Yi-miao; Fang, Bing

    2007-04-01

    The cause of congenital craniofacial abnormalities are very complicated. Understanding of the gene mechanisms of abnormalities taking place are very important for prevention and therapy.DNA sequence analysis provides the fundaments of gene study of the congenital craniofacial abnormalities. Human genome project (HGP) paved the confirmation of candidate gene of the congenital craniofacial abnormalities.Transgenic animal models and gene knockout techniques are effective methods in study of gene function. This paper reviews current gene study in etiopathogenisis analysis of the congenital craniofacial abnormalities.

  17. Craniofacial bone tissue engineering.

    PubMed

    Wan, Derrick C; Nacamuli, Randall P; Longaker, Michael T

    2006-04-01

    Repair and reconstruction of the craniofacial skeleton represents a significant biomedical burden, with thousands of procedures per-formed annually secondary to injuries and congenital malformations. Given the multitude of current approaches, the need for more effective strategies to repair these bone deficits is apparent. This article explores two major modalities for craniofacial bone tissue engineering: distraction osteogenesis and cellular based therapies. Current understanding of the guiding principles for each of these modalities is elaborated on along with the knowledge gained from clinical and investigative studies. By laying this foundation, future directions for craniofacial distraction and cell-based bone engineering have emerged with great promise for the advancement of clinical practice.

  18. Craniofacial distraction osteogenesis.

    PubMed

    Winters, Ryan; Tatum, Sherard A

    2014-11-01

    Distraction osteogenesis (DO) may be the most versatile tool to become available to the craniofacial surgeon in recent years. It can be used in an ever-expanding register of clinical scenarios and offers major advantages over conventional craniofacial techniques in some circumstances. Craniofacial surgery has significant complications, some of which can be mitigated but not eliminated by choosing DO over conventional approaches. Although some DO applications are in their infancy with limited data, this article provides an overview of current uses of this versatile technology. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. 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

  20. Craniofacial growth: evolving paradigms.

    PubMed

    Castaldo, Gennaro; Cerritelli, Francesco

    2015-01-01

    Numerous theories about craniofacial growth have been formulated in the last century. The most influential hypotheses were: genetic, synthetic and functional matrix revisited. Moreover, a large number of experts from different fields tried to explain craniofacial growth and its developmental mechanisms, in order to deliver the best treatment possible to orthodontic patients. The aim of this review is to summarize recent concepts on craniofacial growth, overlap these theories with the development of the general scientific knowledge, and suggest a more integrated multidisciplinary person-based approach. MEDLINE, EMBASE, Pubmed, CINAHL and Google Scholar were screened from inception to February 2014 for relevant papers. Grey literature was considered as part of the search. The influence of new scientific discoveries and intuitions about craniofacial growth produced further insights in orthodontics care, shifting the paradigm from a pre-determined, sectorial treatment to an individualized, multidisciplinary patient-centered approach aiming to enhance the quality of orthodontic assistance.

  1. 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.

  2. 75 FR 4833 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research... personal privacy. Name of Committee: National Institute of Dental and Craniofacial Research Special... Inst of Dental & Craniofacial Research, NIH 6701 Democracy Blvd, room 672, MSC 4878, Bethesda, md 20892...

  3. Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial Development.

    PubMed

    Fakhouri, Walid D; Metwalli, Kareem; Naji, Ali; Bakhiet, Sarah; Quispe-Salcedo, Angela; Nitschke, Larissa; Kousa, Youssef A; Schutte, Brian C

    2017-08-02

    Interferon Regulatory Factor 6 (IRF6) and TWIST1 are transcription factors necessary for craniofacial development. Human genetic studies showed that mutations in IRF6 lead to cleft lip and palate and mandibular abnormalities. In the mouse, we found that loss of Irf6 causes craniosynostosis and mandibular hypoplasia. Similarly, mutations in TWIST1 cause craniosynostosis, mandibular hypoplasia and cleft palate. Based on this phenotypic overlap, we asked if Irf6 and Twist1 interact genetically during craniofacial formation. While single heterozygous mice are normal, double heterozygous embryos (Irf6 (+/-) ; Twist1 (+/-) ) can have severe mandibular hypoplasia that leads to agnathia and cleft palate at birth. Analysis of spatiotemporal expression showed that Irf6 and Twist1 are found in different cell types. Consistent with the intercellular interaction, we found reduced expression of Endothelin1 (EDN1) in mandible and transcription factors that are critical for mandibular patterning including DLX5, DLX6 and HAND2, were also reduced in mesenchymal cells. Treatment of mandibular explants with exogenous EDN1 peptides partially rescued abnormalities in Meckel's cartilage. In addition, partial rescue was observed when double heterozygous embryos also carried a null allele of p53. Considering that variants in IRF6 and TWIST1 contribute to human craniofacial defects, this gene-gene interaction may have implications on craniofacial disorders.

  4. Intraflagellar transport 88 (IFT88) is crucial for craniofacial development in mice and is a candidate gene for human cleft lip and palate.

    PubMed

    Tian, Hua; Feng, Jifan; Li, Jingyuan; Ho, Thach-Vu; Yuan, Yuan; Liu, Yang; Brindopke, Frederick; Figueiredo, Jane C; Magee, William; Sanchez-Lara, Pedro A; Chai, Yang

    2017-03-01

    Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G > C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting. In order to evaluate the function of IFT88 in regulating craniofacial development, we generated Wnt1-Cre;Ift88fl/fl mice to eliminate Ift88 specifically in cranial neural crest (CNC) cells. Wnt1-Cre;Ift88fl/flpups died at birth due to severe craniofacial defects including bilateral cleft lip and palate and tongue agenesis, following the loss of the primary cilia in the CNC-derived palatal mesenchyme. Loss of Ift88 also resulted in a decrease in neural crest cell proliferation during early stages of palatogenesis as well as a downregulation of the Shh signaling pathway in the palatal mesenchyme. Importantly, Osr2KI-Cre;Ift88fl/flmice, in which Ift88 is lost specifically in the palatal mesenchyme, exhibit isolated cleft palate. Taken together, our results demonstrate that IFT88 has a highly conserved function within the primary cilia of the CNC-derived mesenchyme in the lip and palate region in mice and is a strong candidate as an orofacial clefting gene in humans. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Clinical application of cultured autologous human auricular chondrocytes with autologous serum for craniofacial or nasal augmentation and repair.

    PubMed

    Yanaga, Hiroko; Yanaga, Katsu; Imai, Keisuke; Koga, Mika; Soejima, Chie; Ohmori, Kitaro

    2006-05-01

    The repair of a craniofacial or nose deformity requires a large volume of reconstructive material. A conventional cartilage graft does not provide a sufficient volume of reconstructive material. Therefore, augmentation of the facial form to the defect shape is quite difficult. The authors developed a new treatment method that provides a sufficiently large volume of reconstructive material and enables an easier reconstruction of the original shape. Ages of the patients ranged between 9 and 63 years. Approximately 1 cm of auricular cartilage was collected from the auricular concha. Isolated chondrocytes were cultured with autologous serum that accelerates cell proliferation. The cells were subcultured and formed a gel-form mass. This mass, together with autologous serum, was grafted (injected) on the periosteum and into the subcutaneous pocket. The volume of grafted cultured chondrocytes ranged from 1.7 to 40 cc (1 to 5 x 10(7) cells/cc). The lesion changed from soft gel form into hard cartilage tissues within 2 to 3 weeks and stabilized. Excellent or good satisfactory results were obtained in all patients and have been maintained for periods ranging from 3 to 34 months. No patient experienced absorption of cultured chondrocytes. Biopsy of the newly formed tissues showed that it was an elastic cartilage derived from the original tissue. A small number of chondrocytes obtained from a 1-cm auricular cartilage are successfully cultured into a large number of cells in a gel form. Those autologous auricular chondrocytes in a gel form allow for the repair of complicated shapes of the defect area. This technique is applicable to various treatments for craniofacial or nose deformity.

  6. Influence of congenital facial nerve palsy on craniofacial growth in craniofacial microsomia.

    PubMed

    Choi, Jaehoon; Park, Sang Woo; Kwon, Geun-Yong; Kim, Sang-Hyun; Hur, Ji An; Baek, Seung-Hak; Kim, Jae Chan; Choi, Tae Hyun; Kim, Sukwha

    2014-11-01

    Facial muscles are of major importance in human craniofacial growth and development. The purpose of our study was to investigate whether congenital facial nerve palsy influences craniofacial growth in craniofacial microsomia. Fifty-one patients with unilateral craniofacial microsomia and no history of craniofacial skeletal surgery whose radiographs were taken after craniofacial growth was complete were included in this study. These patients were divided into groups in which the facial nerve was involved or uninvolved. The authors evaluated a total of seven measurement items to analyze the midface and mandibular asymmetry. Twenty patients had facial nerve involvement, and 31 had no involvement. None of the measurement items revealed any significant differences between the facial nerve-involved group and the uninvolved group within the same modified Pruzansky grade. There was no correlation between the type of facial nerve involvement and the measurement items. In relationships among the measurement items within each group, maxillary asymmetry was indirectly correlated with mandibular asymmetry or midline deviation through the occlusal plane angle in the uninvolved groups. However, in the facial nerve-involved group, the relationships disappeared. When the correlations in the facial nerve-involved group were compared with those of the uninvolved group, the relationships in the uninvolved group appeared more significant than in the facial nerve-involved group. The loss of relationships between the upper and lower jaw in the facial nerve-involved group might have been caused by subtle changes, which occur in midfacial bones and in the mandible due to facial nerve palsy. The main limitation of our study is that aside from facial nerve palsy, craniofacial microsomia has many factors that can influence craniofacial growth, such as hypoplasia of the mandibular condyle and soft tissue deficiencies. Copyright © 2014 British Association of Plastic, Reconstructive and

  7. Hyponatremia in the postoperative craniofacial pediatric patient population: a connection to cerebral salt wasting syndrome and management of the disorder.

    PubMed

    Levine, J P; Stelnicki, E; Weiner, H L; Bradley, J P; McCarthy, J G

    2001-11-01

    Hyponatremia after cranial vault remodeling has been noted in a pediatric patient population. If left untreated, the patients may develop a clinical hypoosmotic condition that can lead to cerebral edema, increased intracranial pressure, and eventually, to central nervous system and circulatory compromise. The hyponatremia has traditionally been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH); however, in our patients the treatment has been resuscitation with normal saline as opposed to fluid restriction (the accepted treatment of SIADH), thus placing the diagnosis of SIADH in question. Patients who developed hyponatremia after intracranial injury or surgery were, until recently, grouped together as having SIADH. However, there are diagnosis and treatment differences between SIADH and another distinct but poorly understood disorder that is designated cerebral salt wasting syndrome (CSW). CSW is associated with increased urine output and increased urine sodium concentration and volume contraction, and it is frequently seen after a central nervous system trauma. We therefore developed a prospective study to evaluate the cause of the sodium imbalance.Ten consecutive pediatric patients who underwent intracranial surgery for various craniosynostotic disorders were postoperatively monitored in the pediatric intensive care unit for hemodynamic, respiratory, and fluid management. The first four patients were evaluated for electrolyte changes and overall fluid balance to determine the consistency with which these changes occurred. The remaining six patients had daily (including preoperative) measurement of serum electrolytes, urine electrolytes, urine osmolarity, serum antidiuretic hormone (ADH), aldosterone, and atrial natriuretic hormone (ANH). All patients received normal saline intravenous replacement fluid in the postoperative period. All of the patients developed a transient hyponatremia postoperatively, despite normal saline

  8. The Ubiquitin E3 Ligase NOSIP Modulates Protein Phosphatase 2A Activity in Craniofacial Development

    PubMed Central

    Hoffmeister, Meike; Prelle, Carola; Küchler, Philipp; Kovacevic, Igor; Moser, Markus; Müller-Esterl, Werner; Oess, Stefanie

    2014-01-01

    Holoprosencephaly is a common developmental disorder in humans characterised by incomplete brain hemisphere separation and midface anomalies. The etiology of holoprosencephaly is heterogeneous with environmental and genetic causes, but for a majority of holoprosencephaly cases the genes associated with the pathogenesis could not be identified so far. Here we report the generation of knockout mice for the ubiquitin E3 ligase NOSIP. The loss of NOSIP in mice causes holoprosencephaly and facial anomalies including cleft lip/palate, cyclopia and facial midline clefting. By a mass spectrometry based protein interaction screen we identified NOSIP as a novel interaction partner of protein phosphatase PP2A. NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice. We conclude, that NOSIP is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans. PMID:25546391

  9. A survey of dentists in the United States regarding a specialty in craniofacial pain.

    PubMed

    Simmons, H Clifton; Kilpatrick, Steven R

    2004-01-01

    In an effort to explore whether a specialty for craniofacial pain is warranted, the American Academy of Craniofacial Pain (AACP) commissioned an opinion survey of dentists. The survey population (N=4000) was stratified by specialty, so that dentists in affected areas would be adequately represented: 500 orthodontists and dentofacial orthopedists, 500 oral and maxillofacial surgeons, 500 periodontists, 500 prosthodontists, and 2,000 general practitioners. A total of 930 dentists responded for a 23.2% response rate. The survey had multiple purposes: 1. to measure the percentage of craniofacial pain patients perceived in dental patient populations; 2. to determine whether each dentist prefers to treat the disorder or; 3. prefers to refer craniofacial pain patients to clinicians specializing in the disorder; and 4. whether dentists favor/oppose the formation of a craniofacial pain specialty. The respondents' perception of the prevalence of craniofacial pain among their patients was 13.9%. A majority of the responding dentists, 54.7%, are in favor of a craniofacial pain specialty. Overall, 65% of dentists treat craniofacial pain patients, although more than half, 55%, of all dentists also refer such patients. Even 43.6% of dentists who regularly treat craniofacial pain favor a specialty, while 76% of those who do not treat such patients favor the specialty. The data presented here advocate development of a dental specialty in craniofacial pain.

  10. A human YAC transgene rescues craniofacial and neural tube development in PDGFRalpha knockout mice and uncovers a role for PDGFRalpha in prenatal lung growth.

    PubMed

    Sun, T; Jayatilake, D; Afink, G B; Ataliotis, P; Nistér, M; Richardson, W D; Smith, H K

    2000-11-01

    The platelet-derived growth factor alpha-receptor (PDGFRalpha) plays a vital role in the development of vertebrate embryos, since mice lacking PDGFRalpha die in mid-gestation. PDGFRalpha is expressed in several types of migratory progenitor cells in the embryo including cranial neural crest cells, lung smooth muscle progenitors and oligodendrocyte progenitors. To study PDGFRalpha gene regulation and function during development, we generated transgenic mice by pronuclear injection of a 380 kb yeast artificial chromosome (YAC) containing the human PDGFRalpha gene. The YAC transgene was expressed in neural crest cells, rescued the profound craniofacial abnormalities and spina bifida observed in PDGFRalpha knockout mice and prolonged survival until birth. The ultimate cause of death was respiratory failure due to a defect in lung growth, stemming from failure of the transgene to be expressed correctly in lung smooth muscle progenitors. However, the YAC transgene was expressed faithfully in oligodendrocyte progenitors, which was not previously observed with plasmid-based transgenes containing only upstream PDGFRalpha control sequences. Our data illustrate the complexity of PDGFRalpha genetic control, provide clues to the location of critical regulatory elements and reveal a requirement for PDGF signalling in prenatal lung growth, which is distinct from the known requirement in postnatal alveogenesis. In addition, we found that the YAC transgene did not prolong survival of Patch mutant mice, indicating that genetic defects outside the PDGFRalpha locus contribute to the early embryonic lethality of Patch mice.

  11. A Noncoding Expansion in EIF4A3 Causes Richieri-Costa-Pereira Syndrome, a Craniofacial Disorder Associated with Limb Defects

    PubMed Central

    Favaro, Francine P.; Alvizi, Lucas; Zechi-Ceide, Roseli M.; Bertola, Debora; Felix, Temis M.; de Souza, Josiane; Raskin, Salmo; Twigg, Stephen R.F.; Weiner, Andrea M.J.; Armas, Pablo; Margarit, Ezequiel; Calcaterra, Nora B.; Andersen, Gregers R.; McGowan, Simon J.; Wilkie, Andrew O.M.; Richieri-Costa, Antonio; de Almeida, Maria L.G.; Passos-Bueno, Maria Rita

    2014-01-01

    Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity-by-descent analysis in 17 genealogies. Sequencing strategies identified an expansion of a region with several repeats of 18- or 20-nucleotide motifs in the 5′ untranslated region (5′ UTR) of EIF4A3, which contained from 14 to 16 repeats in the affected individuals and from 3 to 12 repeats in 520 healthy individuals. A missense substitution of a highly conserved residue likely to affect the interaction of eIF4AIII with the UPF3B subunit of the exon junction complex in trans with an expanded allele was found in an unrelated individual with an atypical presentation, thus expanding mutational mechanisms and phenotypic diversity of RCPS. EIF4A3 transcript abundance was reduced in both white blood cells and mesenchymal cells of RCPS-affected individuals as compared to controls. Notably, targeting the orthologous eif4a3 in zebrafish led to underdevelopment of several craniofacial cartilage and bone structures, in agreement with the craniofacial alterations seen in RCPS. Our data thus suggest that RCPS is caused by mutations in EIF4A3 and show that EIF4A3, a gene involved in RNA metabolism, plays a role in mandible, laryngeal, and limb morphogenesis. PMID:24360810

  12. Cichlid fishes as a model to understand normal and clinical craniofacial variation.

    PubMed

    Powder, Kara E; Albertson, R Craig

    2016-07-15

    We have made great strides towards understanding the etiology of craniofacial disorders, especially for 'simple' Mendelian traits. However, the facial skeleton is a complex trait, and the full spectrum of genetic, developmental, and environmental factors that contribute to its final geometry remain unresolved. Forward genetic screens are constrained with respect to complex traits due to the types of genes and alleles commonly identified, developmental pleiotropy, and limited information about the impact of environmental interactions. Here, we discuss how studies in an evolutionary model - African cichlid fishes - can complement traditional approaches to understand the genetic and developmental origins of complex shape. Cichlids exhibit an unparalleled range of natural craniofacial morphologies that model normal human variation, and in certain instances mimic human facial dysmorphologies. Moreover, the evolutionary history and genomic architecture of cichlids make them an ideal system to identify the genetic basis of these phenotypes via quantitative trait loci (QTL) mapping and population genomics. Given the molecular conservation of developmental genes and pathways, insights from cichlids are applicable to human facial variation and disease. We review recent work in this system, which has identified lbh as a novel regulator of neural crest cell migration, determined the Wnt and Hedgehog pathways mediate species-specific bone morphologies, and examined how plastic responses to diet modulate adult facial shapes. These studies have not only revealed new roles for existing pathways in craniofacial development, but have identified new genes and mechanisms involved in shaping the craniofacial skeleton. In all, we suggest that combining work in traditional laboratory and evolutionary models offers significant potential to provide a more complete and comprehensive picture of the myriad factors that are involved in the development of complex traits. Copyright © 2015

  13. The influence of gender and sex steroids on craniofacial nociception.

    PubMed

    Cairns, Brian E

    2007-02-01

    Several pain conditions localized to the craniofacial region show a remarkable sex-related difference in their prevalence. These conditions include temporomandibular disorders and burning mouth syndrome as well as tension-type, migraine, and cluster headaches. The mechanisms that underlie sex-related differences in the prevalence of these craniofacial pain conditions remain obscure and likely involve both physiological and psychosocial factors. In terms of physiological factors relevant to the development of headache, direct evidence of sex-related differences in the properties of dural afferent fibers or durally activated second-order trigeminal sensory neurons has yet to be provided. There is, however, evidence for sex-related differences in the response properties of afferent fibers and second-order trigeminal sensory neurons that convey nociceptive input from other craniofacial tissues associated with sex-related differences in chronic pain conditions, such as those that innervate the masseter muscle and temporomandibular joint. Further, modulation of craniofacial nociceptive input by opioidergic receptor mechanisms appears to be dependent on biological sex. Research into mechanisms that may contribute to sex-related differences in trigeminal nociceptive processing has primarily focused on effect of the female sex hormone estrogen, which appears to alter the excitability of trigeminal afferent fibers and sensory neurons to noxious stimulation of craniofacial tissues. This article discusses current knowledge of potential physiological mechanisms that could contribute to sex-related differences in certain craniofacial pain conditions.

  14. Qualitative approaches in craniofacial research.

    PubMed

    Nelson, Pauline A

    2009-05-01

    This article proposes the customary use of qualitative methods as complementary research tools to enhance the evidence base in the craniofacial field. The recognition given to qualitative approaches in other healthcare areas and their value in enhancing understanding of lay and professional beliefs and behaviors is contrasted with the paucity of qualitative studies to date in the craniofacial field. Research tools from the qualitative repertoire are briefly introduced and their underpinning principles are explained. The contribution made to research with children and families in wider healthcare areas and in the craniofacial field to date is outlined. Future potential applications of these methods to craniofacial research are discussed. It is suggested that qualitative methods be integrated into craniofacial research as part of the standard toolbox of inquiry, and that interdisciplinary collaborations with colleagues from the social sciences appropriately skilled in the methods should be developed.

  15. Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model of FASD

    PubMed Central

    McCarthy, Neil; Wetherill, Leah; Lovely, C. Ben; Swartz, Mary E.; Foroud, Tatiana M.; Eberhart, Johann K.

    2013-01-01

    Human birth defects are highly variable and this phenotypic variability can be influenced by both the environment and genetics. However, the synergistic interactions between these two variables are not well understood. Fetal alcohol spectrum disorders (FASD) is the umbrella term used to describe the wide range of deleterious outcomes following prenatal alcohol exposure. Although FASD are caused by prenatal ethanol exposure, FASD are thought to be genetically modulated, although the genes regulating sensitivity to ethanol teratogenesis are largely unknown. To identify potential ethanol-sensitive genes, we tested five known craniofacial mutants for ethanol sensitivity: cyp26b1, gata3, pdgfra, smad5 and smoothened. We found that only platelet-derived growth factor receptor alpha (pdgfra) interacted with ethanol during zebrafish craniofacial development. Analysis of the PDGF family in a human FASD genome-wide dataset links PDGFRA to craniofacial phenotypes in FASD, prompting a mechanistic understanding of this interaction. In zebrafish, untreated pdgfra mutants have cleft palate due to defective neural crest cell migration, whereas pdgfra heterozygotes develop normally. Ethanol-exposed pdgfra mutants have profound craniofacial defects that include the loss of the palatal skeleton and hypoplasia of the pharyngeal skeleton. Furthermore, ethanol treatment revealed latent haploinsufficiency, causing palatal defects in ∼62% of pdgfra heterozygotes. Neural crest apoptosis partially underlies these ethanol-induced defects in pdgfra mutants, demonstrating a protective role for Pdgfra. This protective role is mediated by the PI3K/mTOR pathway. Collectively, our results suggest a model where combined genetic and environmental inhibition of PI3K/mTOR signaling leads to variability within FASD. PMID:23861062

  16. Elastic Properties of Chimpanzee Craniofacial Cortical Bone.

    PubMed

    Gharpure, Poorva; Kontogiorgos, Elias D; Opperman, Lynne A; Ross, Callum F; Strait, David S; Smith, Amanda; Pryor, Leslie C; Wang, Qian; Dechow, Paul C

    2016-12-01

    Relatively few assessments of cranial biomechanics formally take into account variation in the material properties of cranial cortical bone. Our aim was to characterize the elastic properties of chimpanzee craniofacial cortical bone and compare these to the elastic properties of dentate human craniofacial cortical bone. From seven cranial regions, 27 cylindrical samples were harvested from each of five chimpanzee crania. Assuming orthotropy, axes of maximum stiffness in the plane of the cortical plate were derived using modified equations of Hooke's law in a Mathcad program. Consistent orientations among individuals were observed in the zygomatic arch and alveolus. The density of cortical bone showed significant regional variation (P < 0.001). The elastic moduli demonstrated significant differences between sites, and a distinct pattern where E3  > E2  > E1 . Shear moduli were significantly different among regions (P < 0.001). The pattern by which chimpanzee cranial cortical bone varies in elastic properties resembled that seen in humans, perhaps suggesting that the elastic properties of craniofacial bone in fossil hominins can be estimated with at least some degree of confidence. Anat Rec, 299:1718-1733, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Secretory COPII coat component Sec23a is essential for craniofacial chondrocyte maturation.

    PubMed

    Lang, Michael R; Lapierre, Lynne A; Frotscher, Michael; Goldenring, James R; Knapik, Ela W

    2006-10-01

    An increasing number of human disorders have been linked to mutations in genes of the secretory pathway. The chemically induced zebrafish crusher variant results in malformed craniofacial skeleton, kinked pectoral fins and a short body length. By positional cloning, we identified a nonsense mutation converting leucine to a stop codon (L402X) in the sec23a gene, an integral component of the COPII complex, which is critical for anterograde protein trafficking between endoplasmic reticulum and Golgi apparatus. Zebrafish crusher mutants develop normally until the onset of craniofacial chondrogenesis. crusher chondrocytes accumulate proteins in a distended endoplasmic reticulum, resulting in severe reduction of cartilage extracellular matrix (ECM) deposits, including type II collagen. We demonstrate that the paralogous gene sec23b is also an essential component of the ECM secretory pathway in chondrocytes. In contrast, knockdown of the COPI complex does not hinder craniofacial morphogenesis. As SEC23A lesions cause the cranio-lenticulo-sutural dysplasia syndrome, crusher provides the first vertebrate model system that links the biology of endoplasmic reticulum to Golgi trafficking with a clinically relevant dysmorphology.

  18. Emerging Peripheral Receptor Targets for Deep-tissue Craniofacial Pain Therapies

    PubMed Central

    Ambalavanar, R.; Dessem, D.

    2009-01-01

    While effective therapies are available for some types of craniofacial pain, treatments for deep-tissue craniofacial pain such as temporomandibular disorders are less efficacious. Several ion channels and receptors which are prominent in craniofacial nociceptive mechanisms have been identified on trigeminal primary afferent neurons. Many of these receptors and channels exhibit unusual distributions compared with extracranial regions. For example, expression of the ATP receptor P2X3 is strongly implicated in nociception and is more abundant on trigeminal primary afferent neurons than analogous extracranial neurons, making them potentially productive targets specifically for craniofacial pain therapies. The initial part of this review therefore focuses on P2X3 as a potential therapeutic target to treat deep-tissue craniofacial pain. In the trigeminal ganglion, P2X3 receptors are often co-expressed with the nociceptive neuropeptides CGRP and SP. Therefore, we discuss the role of CGRP and SP in deep-tissue craniofacial pain and suggest that neuropeptide antagonists, which have shown promise for the treatment of migraine, may have wider therapeutic potential, including the treatment of deep-tissue craniofacial pain. P2X3, TRPV1, and ASIC3 are often co-expressed in trigeminal neurons, implying the formation of functional complexes that allow craniofacial nociceptive neurons to respond synergistically to altered ATP and pH in pain. Future therapeutics for craniofacial pain thus might be more efficacious if targeted at combinations of P2X3, CGRP, TRPV1, and ASIC3. PMID:19329451

  19. Emerging peripheral receptor targets for deep-tissue craniofacial pain therapies.

    PubMed

    Ambalavanar, R; Dessem, D

    2009-03-01

    While effective therapies are available for some types of craniofacial pain, treatments for deep-tissue craniofacial pain such as temporomandibular disorders are less efficacious. Several ion channels and receptors which are prominent in craniofacial nociceptive mechanisms have been identified on trigeminal primary afferent neurons. Many of these receptors and channels exhibit unusual distributions compared with extracranial regions. For example, expression of the ATP receptor P2X(3) is strongly implicated in nociception and is more abundant on trigeminal primary afferent neurons than analogous extracranial neurons, making them potentially productive targets specifically for craniofacial pain therapies. The initial part of this review therefore focuses on P2X(3) as a potential therapeutic target to treat deep-tissue craniofacial pain. In the trigeminal ganglion, P2X(3) receptors are often co-expressed with the nociceptive neuropeptides CGRP and SP. Therefore, we discuss the role of CGRP and SP in deep-tissue craniofacial pain and suggest that neuropeptide antagonists, which have shown promise for the treatment of migraine, may have wider therapeutic potential, including the treatment of deep-tissue craniofacial pain. P2X(3), TRPV1, and ASIC3 are often co-expressed in trigeminal neurons, implying the formation of functional complexes that allow craniofacial nociceptive neurons to respond synergistically to altered ATP and pH in pain. Future therapeutics for craniofacial pain thus might be more efficacious if targeted at combinations of P2X(3), CGRP, TRPV1, and ASIC3.

  20. Differences between sliding semi-landmark methods in geometric morphometrics, with an application to human craniofacial and dental variation

    PubMed Central

    Ivan Perez, S; Bernal, Valeria; Gonzalez, Paula N

    2006-01-01

    Over the last decade, geometric morphometric methods have been applied increasingly to the study of human form. When too few landmarks are available, outlines can be digitized as series of discrete points. The individual points must be slid along a tangential direction so as to remove tangential variation, because contours should be homologous from subject to subject whereas their individual points need not. This variation can be removed by minimizing either bending energy (BE) or Procrustes distance (D) with respect to a mean reference form. Because these two criteria make different assumptions, it becomes necessary to study how these differences modify the results obtained. We performed bootstrapped-based Goodall's F-test, Foote's measurement, principal component (PC) and discriminant function analyses on human molars and craniometric data to compare the results obtained by the two criteria. Results show that: (1) F-scores and P-values were similar for both criteria; (2) results of Foote's measurement show that both criteria yield different estimates of within- and between-sample variation; (3) there is low correlation between the first PC axes obtained by D and BE; (4) the percentage of correct classification is similar for BE and D, but the ordination of groups along discriminant scores differs between them. The differences between criteria can alter the results when morphological variation in the sample is small, as in the analysis of modern human populations. PMID:16761977

  1. Penetrating craniofacial arrow injury.

    PubMed

    Jain, Dk; Aggarwal, Gaurav; Lubana, Ps; Moses, Sonia

    2010-01-01

    Arrow injuries are an extinct form of injury in most parts of the developed world, but are still seen, albeit infrequently in developing countries. Reports of penetrating injuries of the craniofacial region secondary to projectiles are few and far between. The morbidity-free outcome of surgical removal, in case of penetrating arrow injuries, despite the delay in presentation and, moreover, in the emergency surgical practice, are the salient points to be remembered whilst managing such cases, for 'what the mind knows is what the eyes see and what the eyes see is what can be practiced'. We report the case of a patient who was attacked by a projectile fired from a crossbow. Immediate surgery under general anesthesia was required to remove the arrow, with utmost care to avoid any neurovascular compromise to the facial nerve, as well as minimize postoperative complications such as otitis media and subsequent meningitis.

  2. Relative size of the eye and orbit: an evolutionary and craniofacial constraint model for examining the etiology and disparate incidence of juvenile-onset myopia in humans.

    PubMed

    Masters, Michael P

    2012-05-01

    The principal aim of this research is to provide a new model for investigating myopia in humans, and contribute to an understanding of the degree to which modern variation and evolutionary change in orbital and overall craniofacial morphology may help explain the common eye form association with this condition. Recent research into long and short-term evolution of the human orbit reveals a number of changes in this feature, and particularly since the Upper Paleolithic. These include a reduction in orbital depth, a decrease in anterior projection of the upper and lower orbital margins, and most notably, a reduction in orbital volume since the Holocene in East Asia. Reduced orbital volume in this geographic region could exacerbate an existing trend in recent hominin evolution toward larger eyes in smaller orbits, and may help explain the unusually high frequency of myopia in East Asian populations. The objective of the current study is to test a null hypothesis of no relationship between a ratio of orbit to eye volume and spherical equivalent refractive error (SER) in a sample of Chinese adults, and examine how relative size of the eye within the orbit relates to SER between the sexes and across the sample population. Analysis of the orbit, eye, and SER reveals a strong relationship between relative size of the eye within the orbit and the severity of myopic refractive error. An orbit/eye ratio of 3 for females and 3.5 for males (or an eye that occupies approximately 34% and 29% of the orbit, respectively), designates a clear threshold at which myopia develops, and becomes progressively worse as the eye continues to occupy a greater proportion of the orbital cavity. These results indicate that relative size of the eye within the orbit is an important factor in the development of myopia, and suggests that individuals with large eyes in small orbits lack space for adequate development of ocular tissues, leading to compression and distortion of the lithesome globe

  3. Craniofacial fibrous dysplasia: A 10-case series.

    PubMed

    Couturier, A; Aumaître, O; Gilain, L; Jean, B; Mom, T; André, M

    2017-09-01

    Fibrous dysplasia of bone is a rare sporadic benign congenital condition in which normal cancellous bone is replaced by fibro-osseous tissue with immature osteogenesis. Sarcomatous transformation is exceptional. Lesions may involve one bone (monostotic) or several (polyostotic). Fibrous dysplasia may be associated with café-au-lait skin macules and endocrinopathy in McCune-Albright syndrome, or with myxoma in Mazabraud's syndrome. We report ten cases of patients followed up for craniofacial fibrous dysplasia in our center between 2010 and 2015. Mean age was 43 years (range, 10-72 years). Clinical symptoms comprised headache (n=3) and sensorineural disorder: recurrent anterior uveitis (n=1), visual acuity loss, epiphora and vestibular syndrome (n=1), and hearing loss (n=1). All cases were monostotic. The sphenoid bone was most commonly involved (n=5), followed by the ethmoid (n=1), frontal (n=1), fronto-ethmoid (n=1), temporal (n=1) and fronto-ethmoido-sphenoid (n=1) bones. Five patients were treated with intravenous pamidronate, a bisphosphonate: evolution was favorable for 3 of them at 1-6 months after treatment initiation, with resolution of headache or vestibular syndrome; the other 2 patients were stable. Two patients were operated on. Diagnosis of craniofacial fibrous dysplasia should be considered in case of headache, neuralgia, sensory disorder, functional disorder or infectious ENT complications. A medico-surgical approach is useful for these patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Genetics Home Reference: craniofacial microsomia

    MedlinePlus

    ... Luquetti DV, Hing AV. Craniofacial Microsomia Overview. 2009 Mar 19 [updated 2014 Oct 9]. In: Pagon RA, ... 9. doi: 10.3174/ajnr.A2072. Epub 2010 Mar 18. Review. Citation on PubMed Johnson JM, Moonis ...

  5. 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.

  6. 78 FR 24761 - National Institute of Dental & Craniofacial Research; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research.... App.), notice is hereby given of a meeting of the National Advisory Dental and Craniofacial Research... or other reasonable accommodations, should notify the Contact Person listed below in advance of...

  7. 76 FR 80953 - National Institute of Dental & Craniofacial Research; Notice of Meeting

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    2011-12-27

    ... HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research.... App.), notice is hereby given of a meeting of the National Advisory Dental and Craniofacial Research... or other reasonable accommodations, should notify the Contact Person listed below in advance of...

  8. 75 FR 13561 - National Institute of Dental & Craniofacial Research; Notice of Meeting

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    ... HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research.... App.), notice is hereby given of a meeting of the National Advisory Dental and Craniofacial Research... or other reasonable accommodations, should notify the Contact Person listed below in advance of...

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    ... HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research.... App.), notice is hereby given of a meeting of the National Advisory Dental and Craniofacial Research... or other reasonable accommodations, should notify the Contact Person listed below in advance of...

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  15. 77 FR 74674 - National Institute of Dental & Craniofacial Research; Notice of Meeting

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    2012-12-17

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  16. 75 FR 7486 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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    2010-02-19

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  17. 75 FR 28031 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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    2010-05-19

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  18. 75 FR 4833 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

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    2010-01-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research.... of Dental & Craniofacial Research, National Institutes of Health, 45 Center Dr., Rm 4AN 32J, Bethesda...

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  20. 75 FR 55592 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research... Dental and Craniofacial Research Council, September 27, 2010, 8:30 a.m. to September 27, 2010, 3 p.m...

  1. 78 FR 65348 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research... Dental and Craniofacial Research Special Emphasis Panel, October 21, 2013, 9:00 a.m. to October 21, 2013...

  2. 78 FR 65343 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research... Dental and Craniofacial Research Special Emphasis Panel, October 7, 2013, 10:00 a.m. to October 7, 2013...

  3. The molecular basis of human keratin disorders.

    PubMed

    Arin, Meral Julia

    2009-05-01

    Keratins are cytoskeletal proteins that provide structural support to epithelial cells and tissues. Perturbation causes cell and tissue fragility and accounts for a large number of genetic disorders in humans. In humans, 54 functional keratin genes exist and 21 different keratin genes including hair keratins and hair follicle-specific epithelial keratins have been associated with hereditary disorders. Moreover, keratins have been implicated in more complex traits such as liver disease and inflammatory bowel disease. Understanding the molecular basis of keratin disorders has been the basis for improved diagnosis with prognostic implications, genetic counseling and prenatal testing for severe disorders. Besides their mechanical role, keratins have newly identified functions in apoptosis, cell growth, tissue polarity, wound healing and tissue remodeling. Improved understanding of the regulatory functions of keratins may offer novel approaches to overcome current treatment limitations.

  4. Human disorders of peroxisome metabolism and biogenesis.

    PubMed

    Waterham, Hans R; Ferdinandusse, Sacha; Wanders, Ronald J A

    2016-05-01

    Peroxisomes are dynamic organelles that play an essential role in a variety of cellular catabolic and anabolic metabolic pathways, including fatty acid alpha- and beta-oxidation, and plasmalogen and bile acid synthesis. Defects in genes encoding peroxisomal proteins can result in a large variety of peroxisomal disorders either affecting specific metabolic pathways, i.e., the single peroxisomal enzyme deficiencies, or causing a generalized defect in function and assembly of peroxisomes, i.e., peroxisome biogenesis disorders. In this review, we discuss the clinical, biochemical, and genetic aspects of all human peroxisomal disorders currently known.

  5. Craniofacial surgery: present and future.

    PubMed Central

    Whitaker, L A; Schut, L; Randall, P

    1976-01-01

    The possibilities for radical craniofacial restructuring have increased dramatically in the past 6 years with the development of craniofacial surgery. The field developed from a background of patients with major craniofacial birth defects allowing orderly planning and expansion to correction of a multitude of other craniofacial structural problems. The procedures concentrate upon changing the skeletal structures using extensive subperiostial dissection of soft tissue, and adding bone to fill in areas of deficiency. There are three grades of complexity in craniofacial procedures. After extensive soft tissue sub-periostial stripping about the orbits and upper face, the simplest form consists of onlay bone grafts. The next most complicated involves osteotomies to shift the face into a more normal position. In its most complicated form, abnormal proportions of bone are removed and the orbits or cranium are shifted into a new or normal position. We have had experience with 69 patients since September, 1972. Thirty-six have had intracranial procedures. Infection has been the most serious problem, and there have been no instances of death or blindness. A number of lesser problems occur. Future applications of craniofacial surgery are appearing with great frequency as more experience is gained with its uses. It has particular application in acute and late reconstruction of patients with traumatic defects about the face. Preventive osteotomies are an area with great potential, by releasing stenotic areas of bone and allowing the developing brain to mold the upper face and orbits. There is also applicability in surgery of tumors about the craniofacial structure and in cosmetic surgery. Images Fig. 1a. Fig. 1b. Fig. 1c. Fig. 1d. Fig. 1e. Fig. 2a. Fig. 2b. Fig. 2c. PMID:984925

  6. The association between the cervical spine, the stomatognathic system, and craniofacial pain: a critical review.

    PubMed

    Armijo Olivo, Susan; Magee, David J; Parfitt, Martin; Major, Paul; Thie, Norman M R

    2006-01-01

    Craniofacial pain is a term that encompasses pain in the head, face, and related structures. Multiple etiologies and factors may be related to craniofacial pain; however, the association between the cervical spine and its related structures and craniofacial pain is still a topic of debate. The objective of this critical review was to present and analyze the evidence of the associations between the cervical spine, stomatognathic system, and craniofacial pain. A search of the databases Medline, PubMed, Embase, Web of Sciences, Cochrane Library, Cinahl, and HealthStar was conducted for all publications related to the topic in the English and Spanish languages. Relevant information was also derived from reference lists of the retrieved publications. The key words used in the search were cervical spine, cervical vertebrae, neck pain, neck injuries, neck muscles, craniofacial pain, orofacial pain, facial pain, temporomandibular joint pain, and temporomandibular joint disorders. The search provided information referring to the biomechanical, anatomical, and pathological association between craniofacial pain, the stomatognathic system and the cervical spine. The information provided by this review suggests an association between the cervical spine, stomatognathic system, and craniofacial pain, but most of this information is not conclusive and was derived from poor-quality studies (levels 3b, 4, and 5 based on Sackett's classification). Better designed studies are needed in order to clarify the real influence that the cervical spine has in relation to the stomatognathic system and craniofacial pain.

  7. Intrinsic Disorder in the Human Spliceosomal Proteome

    PubMed Central

    Korneta, Iga; Bujnicki, Janusz M.

    2012-01-01

    The spliceosome is a molecular machine that performs the excision of introns from eukaryotic pre-mRNAs. This macromolecular complex comprises in human cells five RNAs and over one hundred proteins. In recent years, many spliceosomal proteins have been found to exhibit intrinsic disorder, that is to lack stable native three-dimensional structure in solution. Building on the previous body of proteomic, structural and functional data, we have carried out a systematic bioinformatics analysis of intrinsic disorder in the proteome of the human spliceosome. We discovered that almost a half of the combined sequence of proteins abundant in the spliceosome is predicted to be intrinsically disordered, at least when the individual proteins are considered in isolation. The distribution of intrinsic order and disorder throughout the spliceosome is uneven, and is related to the various functions performed by the intrinsic disorder of the spliceosomal proteins in the complex. In particular, proteins involved in the secondary functions of the spliceosome, such as mRNA recognition, intron/exon definition and spliceosomal assembly and dynamics, are more disordered than proteins directly involved in assisting splicing catalysis. Conserved disordered regions in spliceosomal proteins are evolutionarily younger and less widespread than ordered domains of essential spliceosomal proteins at the core of the spliceosome, suggesting that disordered regions were added to a preexistent ordered functional core. Finally, the spliceosomal proteome contains a much higher amount of intrinsic disorder predicted to lack secondary structure than the proteome of the ribosome, another large RNP machine. This result agrees with the currently recognized different functions of proteins in these two complexes. PMID:22912569

  8. 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: ...

  9. 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 Parents & Individuals Cleft Lip/Palate & Craniofacial Specialists in Your Area Team Disclaimer States: ...

  10. NEUROLOGICAL ASPECTS OF HUMAN GLYCOSYLATION DISORDERS

    PubMed Central

    Freeze, Hudson H.; Eklund, Erik A.; Ng, Bobby G.; Patterson, Marc C.

    2016-01-01

    This review will present principles of glycosylation, describe the relevant glycosylation pathways and their related disorders, and highlight some of the neurological aspects and issues that continue to challenge researchers. Over 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delay/intellectual disability, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Between these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of mis-glycosylated products afflicting a myriad of processes including cell signaling, cell-cell interaction and cell migration. This vast complexity in glycan composition and function, along with limited analytic tools has impeded the identification of key glycosylated molecules that cause pathologies, and to date few critical target proteins have been pinpointed. PMID:25840006

  11. Modeling autism spectrum disorders with human neurons.

    PubMed

    Beltrão-Braga, Patricia C B; Muotri, Alysson R

    2017-02-01

    Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impaired social communication and interactions and by restricted and repetitive behaviors. Although ASD is suspected to have a heritable or sporadic genetic basis, its underlying etiology and pathogenesis are not well understood. Therefore, viable human neurons and glial cells produced using induced pluripotent stem cells (iPSC) to reprogram cells from individuals affected with ASD provide an unprecedented opportunity to elucidate the pathophysiology of these disorders, providing novel insights regarding ASD and a potential platform to develop and test therapeutic compounds. Herein, we discuss the state of art with regards to ASD modeling, including limitations of this technology, as well as potential future directions. This article is part of a Special Issue entitled SI: Exploiting human neurons.

  12. 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

  13. 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.

  14. Summarizing craniofacial genetics and developmental biology (SCGDB).

    PubMed

    Hall, Brian K

    2014-04-01

    This overview article highlights active areas of research in craniofacial genetics and developmental biology as reflected in presentations given at the 34th annual meeting of the Society of Craniofacial Genetics and Developmental Biology (SCGDB) in Montreal, Quebec on October 11, 2011. This 1-day meeting provided a stimulating occasion that demonstrated the present status of research in craniofacial genetics and developmental biology and where the field is heading. To accompany the abstracts published in this issue I have selected several themes that emerged from the meeting. After discussing the basis on which craniofacial defects/syndromes are classified and investigated, I address the multi-gene basis of craniofacial syndromes with an examination of the roles of Sox9 and FGF receptors in normal and abnormal craniofacial development. I then turn to the knowledge being gained from population-wide and longitudinal cohort studies and from the discovery of new signaling centers that regulate craniofacial development.

  15. Biomaterials for craniofacial bone engineering.

    PubMed

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

    2014-12-01

    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. © International & American Associations for Dental Research.

  16. 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

  17. Neurophysiological assessment of craniofacial pain.

    PubMed

    Galeotti, Francesca; Truini, Andrea; Cruccu, Giorgio

    2006-04-01

    This review deals with the diagnostic usefulness of neurophysiological testing in patients with craniofacial pain. Neurophysiological testing of trigeminal nerve function relies on trigeminal reflexes and laser-evoked potentials (LEPs). This review briefly describes the physiology of trigeminal reflexes and LEPs, reports normal values and highlights the neurophysiological abnormalities in the main clinical conditions.

  18. Craniofacial clefting and sutural dystopia.

    PubMed

    Moore, M H; Edwards, T J; David, D J

    1991-07-01

    Sutural anomalies in conjunction with craniofacial clefting are unusual. A case of median frontal clefting is presented in which there was an absence of a normal metopic suture and replacement by paramedian frontal sutures. The association of an underlying brain anomaly, with attendant surgical difficulties, is noted, as are the radiological techniques of preoperative diagnosis.

  19. Bone Grafts in Craniofacial Surgery

    PubMed Central

    Elsalanty, Mohammed E.; Genecov, David G.

    2009-01-01

    Reconstruction of cranial and maxillofacial defects is a challenging task. The standard reconstruction method has been bone grafting. In this review, we shall describe the biological principles of bone graft healing, as pertinent to craniofacial reconstruction. Different types and sources of bone grafts will be discussed, as well as new methods of bone defect reconstruction. PMID:22110806

  20. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  1. 76 FR 28793 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ... HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research... commercial property such as patentable material, and personal information concerning individuals associated... review and evaluate grant applications. Place: The Dupont Hotel, 1500 New Hampshire Avenue,...

  2. Surgical treatment of craniofacial fibrous dysplasia in adults.

    PubMed

    Bowers, Christian A; Taussky, Philipp; Couldwell, William T

    2014-01-01

    Craniofacial fibrous dysplasia (FD) is a rare disorder that may require neurosurgical expertise for definitive management; however, surgical management of FD in adult patients is uncommon. Although other therapies have been shown to slow progression, the only definitive cure for adult craniofacial FD is complete resection with subsequent reconstruction. The authors review the biological, epidemiologic, clinical, genetic, and radiographic characteristics of adult FD, with an emphasis on surgical management of FD. They present a small series of three adult patients with complex FD that highlights the surgical complexity required in some adult patients with FD. Because of the complex nature of these adult polyostotic craniofacial cases, the authors used neurosurgical techniques specific to the different surgical indications, including a transsphenoidal approach for resection of sphenoidal sinus FD, a transmaxillary approach to decompress the maxillary branch of the trigeminal nerve with widening of the foramen rotundum, and complete calvarial craniectomy with cranioplasty reconstruction. These cases exemplify the diverse range of skull base techniques required in the spectrum of surgical management of adult FD and demonstrate that novel variations on standard neurosurgical approaches to the skull base can provide successful outcomes with minimal complications in adults with complex craniofacial FD.

  3. Advances in gene technology: Human genetic disorders

    SciTech Connect

    Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.

    1984-01-01

    This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

  4. Overdosage of Hand2 causes limb and heart defects in the human chromosomal disorder partial trisomy distal 4q.

    PubMed

    Tamura, Masaru; Hosoya, Masaki; Fujita, Motoi; Iida, Tomoko; Amano, Takanori; Maeno, Akiteru; Kataoka, Taro; Otsuka, Taketo; Tanaka, Shigekazu; Tomizawa, Shuichi; Shiroishi, Toshihiko

    2013-06-15

    Partial trisomy distal 4q (denoted 4q+) is a human chromosomal disorder caused by duplication of the distal end of the long arm of chromosome 4 (Chr4). This disorder manifests typical phenotypes, including craniofacial, renal, heart and thumb developmental defects. Although these clinical features are likely caused by a dosage imbalance in the gene network involving the trisomic region, the causative gene or genes and the molecular bases are largely unknown. Here, we report mouse Recombination-induced mutation 4 (Rim4) as a model animal of 4q+. The Rim4 genome contains an insertion of a 6.5 Mb fragment from mouse chromosome 8 into chromosome 6. This insertion fragment contains 17 genes, including Hand2, that encode the basic helix-loop-helix transcription factor and is syntenic to the distal end of human Chr4, 4q32.3 to 4q34.1, which is responsible for 4q+. A comparison of phenotypes between patients with Rim4 and 4q+ revealed that Rim4 shows direct parallels with many phenotypes of 4q+ such as craniofacial, heart, cervical vertebra and limb deformities. Rebalancing the gene dosage by a genetic cross with Hand2 knockout mice ameliorated symptoms of the heart and limb deformities of Rim4. Conversely, an increase in copy number of Hand2 in wild-type mice recaptures the heart and limb deformities of Rim4. Our results collectively demonstrate that overdosage of Hand2 is a major cause for at least the limb and heart phenotypes of 4q+ and that mouse Rim4 provides a unique animal model for understanding the molecular bases underlying the complex phenotypes of 4q+.

  5. 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

    2016-09-05

    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.

  6. Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development

    PubMed Central

    TeSlaa, Jessica J.; Keller, Abigail N.; Nyholm, Molly K.; Grinblat, Yevgenya

    2013-01-01

    Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) Neural crest induction and migration, and (2) early

  7. Miocene hominoid craniofacial morphology and the emergence of great apes.

    PubMed

    Rae, Todd C

    2004-12-01

    The initial cladogenic event between Hominoidea (apes, including humans) and Cercopithecoidea (Old World monkeys) consisted primarily of changes in the craniofacial region. These changes, seen in taxa commonly known as victoriapithecids and proconsulids, arose in a mosaic fashion. The divergence in the postcranium was more subtle; there are strong suggestions that apes initially adopted a tail-less pronograde arboreal quadrupedalism, while cercopithecoids became better adapted to a more terrestrial lifestyle. Recent phylogenetic analysis suggests that gibbons (Hylobates) have reversed derived craniofacial characters autapomorphically, contradicting the interpretation that the origin of apes sensu stricto coincides with the emergence of suspensory adaptations. The suspensory postcranium evolved later and appeared first in Eurasia; recent palaeobiogeographic reconstructions suggest that suspensory apes subsequently re-colonized Africa, as suggested nearly thirty years ago on neontological grounds. To test whether these two models of hominoid evolution are compatible, catarrhine craniofacial and postcranial traits, including those from Eurasian fossils, were subjected to parsimony analysis. The results demonstrate a mosaic pattern of derived characters, with gibbons reversing some traits of the face, which suggests their derivation from a 'great ape' face. Combined with the palaeobiogeography, a much longer, step-wise transition from primitive catarrhines to extant great apes than previously envisioned is supported. The pattern of craniofacial change is difficult to interpret in functional/adaptational terms, but the origin of brachiation may have arisen through character displacement due to competition with the emerging modern Old World monkey radiation in Eurasia.

  8. 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

  9. 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.

  10. Genetic basis of human circadian rhythm disorders.

    PubMed

    Jones, Christopher R; Huang, Angela L; Ptáček, Louis J; Fu, Ying-Hui

    2013-05-01

    Circadian rhythm disorders constitute a group of phenotypes that usually present as altered sleep-wake schedules. Until a human genetics approach was applied to investigate these traits, the genetic components regulating human circadian rhythm and sleep behaviors remained mysterious. Steady advances in the last decade have dramatically improved our understanding of the genes involved in circadian rhythmicity and sleep regulation. Finding these genes presents new opportunities to use a wide range of approaches, including in vitro molecular studies and in vivo animal modeling, to elevate our understanding of how sleep and circadian rhythms are regulated and maintained. Ultimately, this knowledge will reveal how circadian and sleep disruption contribute to various ailments and shed light on how best to maintain and recover good health.

  11. Desert dust and human health disorders.

    PubMed

    Goudie, Andrew S

    2014-02-01

    Dust storms may originate in many of the world's drylands and have an effect not only on human health in the drylands themselves but also in downwind environments, including some major urban centres, such as Phoenix, Kano, Athens, Madrid, Dubai, Jedda, Tehran, Jaipur, Beijing, Shanghai, Seoul, Taipei, Tokyo, Sydney, Brisbane and Melbourne. In some parts of the world dust storms occur frequently throughout the year. They can transport particulate material, pollutants, and potential allergens over thousands of km from source. The main sources include the Sahara, central and eastern Asia, the Middle East, and parts of the western USA. In some parts of the world, though not all, the frequency of dust storms is changing in response to land use and climatic changes, and in such locations the health implications may become more severe. Data on the PM10 and P2.5 loadings of dust events are discussed, as are various pollutants (heavy metals, pesticides, etc.) and biological components (spores, fungi, bacteria, etc.). Particulate loadings can far exceed healthy levels. Among the human health effects of dust storms are respiratory disorders (including asthma, tracheitis, pneumonia, allergic rhinitis and silicosis) cardiovascular disorders (including stroke), conjunctivitis, skin irritations, meningococcal meningitis, valley fever, diseases associated with toxic algal blooms and mortality and injuries related to transport accidents.

  12. 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

  13. Dental and craniofacial characteristics in a patient with Hutchinson-Gilford progeria syndrome.

    PubMed

    Reichert, Christoph; Gölz, Lina; Götz, Werner; Wolf, Michael; Deschner, James; Jäger, Andreas

    2014-07-01

    The Hutchinson-Gilford progeria syndrome (HGPS) is an exceptionally rare medical disorder caused by mutations in the lamin A/C gene. Affected patients display typical features of premature aging. Beside general medical disorders, these patients have several specific features related to the craniofacial phenotype and the oral cavity. In this article, the dental and craniofacial characteristics of a 9-year-old girl with HGPS are presented. It is the first report addressing orthodontic tooth movement and microbiological features in a HGPS patient. We describe and discuss pathologic findings and provide a detailed histology of the teeth which had to be extracted during initial treatment.

  14. Ribosomopathies: human disorders of ribosome dysfunction

    PubMed Central

    Narla, Anupama

    2010-01-01

    Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, Schwachman-Diamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q− syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases. PMID:20194897

  15. Ribosomopathies: human disorders of ribosome dysfunction.

    PubMed

    Narla, Anupama; Ebert, Benjamin L

    2010-04-22

    Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, Schwachman-Diamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q- syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases.

  16. Natural killer cells in human autoimmune disorders

    PubMed Central

    2013-01-01

    Natural killer (NK) cells are innate lymphocytes that play a critical role in early host defense against viruses. Through their cytolytic capacity and generation of cytokines and chemokines, NK cells modulate the activity of other components of the innate and adaptive immune systems and have been implicated in the initiation or maintenance of autoimmune responses. This review focuses on recent research elucidating a potential immunoregulatory role for NK cells in T-cell and B-cell-mediated autoimmune disorders in humans, with a particular focus on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A better understanding of the contributions of NK cells to the development of autoimmunity may lead to novel therapeutic targets in these diseases. PMID:23856014

  17. The role of sonic hedgehog in normal and abnormal craniofacial morphogenesis.

    PubMed

    Hu, D; Helms, J A

    1999-11-01

    There is growing evidence that implicates a role for Sonic hedgehog (SHH) in morphogenesis of the craniofacial complex. Mutations in human and murine SHH cause midline patterning defects that are manifested in the head as holoprosencephaly and cyclopia. In addition, teratogens such as jervine, which inhibit the response of tissues to SHH, also produce cyclopia. Thus, the loss of SHH signaling during early stages of neural plate patterning has a profound influence of craniofacial morphogenesis. However, the severity of these defects precludes analyses of SHH function during later stages of craniofacial development. We have used an embryonic chick system to study the role of SHH during these later stages of craniofacial development. Using a combination of surgical and molecular experiments, we show here that SHH is essential for morphogenesis of the frontonasal and maxillary processes (FNP and MXPs), which give rise to the mid- and upper face. Transient loss of SHH signaling in the embryonic face inhibits growth of the primordia and results in defects analogous to hypotelorism and cleft lip/palate, characteristics of the mild forms of holoprosencephaly. In contrast, excess SHH leads to a mediolateral widening of the FNP and a widening between the eyes, a condition known as hypertelorism. In severe cases, this widening is accompanied by facial duplications. Collectively, these experiments demonstrate that SHH has multiple and profound effects on the entire spectrum of craniofacial development, and perturbations in SHH signaling are likely to underlie a number of human craniofacial anomalies.

  18. 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

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

    PubMed

    Noack Watt, Kristin E; Achilleos, Annita; Neben, Cynthia L; Merrill, Amy E; Trainor, Paul A

    2016-07-01

    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.

  20. Craniofacial skeletal architecture and obstructive sleep apnoea syndrome severity.

    PubMed

    Costa E Sousa, Rui Augusto; dos Santos Gil, Nuno Alexandre

    2013-12-01

    Obstructive sleep apnoea syndrome (OSAS) is a sleep related breathing disorder caused by pharynx obstruction that often terminates in abrupt arousals and is capable of disrupting physiological sleep profile. Its' severity has been associated, among others, with craniofacial skeletal morphology. To investigate this relationship and elucidate craniofacial skeleton patterns in individuals without obvious maxillofacial abnormalities, 171 OSAS patients were studied with nocturnal polysomnographic record and cephalometric X-ray (24 variables). Cephalometric variables were compared between three apnoea/hypopnoea index (AHI) groups (AHI ≤ 15; 15 < AHI < 30; AHI ≥ 30) and uni/multivariate analysis between cephalometric variables and AHI were performed. The patients were predominantly men (83%), with a mean age of 48.1 years. Mean BMI and AHI were 28.4 kg/m(2) and 26.2, respectively. Most cephalometric variables differed among the three AHI groups. Fifteen cephalometric variables showed a correlation with AHI. Five cephalometric variables and BMI were independent AHI predictors. Cephalometric variables were better AHI predictors in normal weight patients. Significant evidence of craniofacial skeleton influence was found on OSAS severity, caudalization of the hyoid and lower sagittal facial projection being the most important patterns. From the cephalometric variables analysed, the hypopharynx calibre demonstrated a higher predictive value for AHI, independently of BMI.

  1. Advances in congenital craniofacial surgery.

    PubMed

    Tatum, S A

    1999-01-01

    Surgery for the correction of craniofacial anomalies has come a long way since its beginnings more than three decades ago. Throughout this period numerous developments have occurred in diagnosis and management, as well as a better understanding of the etiology of craniofacial anomalies. Significant technological advancements in imaging have allowed for more precise diagnosis and surgical planning. Quantitative analysis techniques have been developed allowing for more precise results analysis. Nonsurgical management techniques have improved, as has the understanding of the proper utilization of nonsurgical treatment. Most nonsynostotic cases of head shape abnormality can be successfully managed nonsurgically. Improvements in surgical management include ways of diminishing the need for transfusions. Operative technical refinements also allow for improved results. The discovery of intracranial migration of rigid fixation hardware has led to decreased utilization of the metallic implants. Bone cements and absorbable plating systems promise further enhancements. Distraction osseogenesis allows skeletal changes to be made gradually reducing risks. Finally, the etiologies of craniosynostosis are being elucidated and promise to lead to more elegant management, reducing or alleviating the need for surgery. Genetic manipulation may eliminate many of these problems.

  2. Human rights, bioethics, and mental disorder.

    PubMed

    Fennell, Phil

    2008-03-01

    This article considers the international human rights instruments which set minimum standards for the content and use of mental health legislation, and the extent to which they represent 'hard law' (binding and enforceable in domestic or international courts) or 'soft law' which is not strictly binding in the same sense but which may provide persuasive authority or may be used in debate to embarrass a Government into compliance. The article considers the extent to which these various instruments impose both 'negative obligations' on states not to interfere with rights such as physical integrity or protection against arbitrary detention and 'positive' obligations on states to take positive steps to uphold the rights of individuals. The article on the case law under the European Convention on Human Rights showing how 'soft law' sources are increasingly used by the Strasbourg Court as aids to construing the scope of Convention rights. The article concludes by suggesting that whilst mentally disordered people may be afforded different treatment in relation to general bioethics instruments on the international plane, they are also entitled to rights under Disability Conventions which enjoin states to take positive steps to promote equal treatment, social inclusion and protection against discrimination and stigma.

  3. RSK2 is a modulator of craniofacial development.

    PubMed

    Laugel-Haushalter, Virginie; Paschaki, Marie; Marangoni, Pauline; Pilgram, Coralie; Langer, Arnaud; Kuntz, Thibaut; Demassue, Julie; Morkmued, Supawich; Choquet, Philippe; Constantinesco, André; Bornert, Fabien; Schmittbuhl, Matthieu; Pannetier, Solange; Viriot, Laurent; Hanauer, André; Dollé, Pascal; Bloch-Zupan, Agnès

    2014-01-01

    The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized. We examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1). Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) was performed at various stages of odontogenesis in wild-type (WT) mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro. This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets.

  4. RSK2 Is a Modulator of Craniofacial Development

    PubMed Central

    Laugel-Haushalter, Virginie; Paschaki, Marie; Marangoni, Pauline; Pilgram, Coralie; Langer, Arnaud; Kuntz, Thibaut; Demassue, Julie; Morkmued, Supawich; Choquet, Philippe; Constantinesco, André; Bornert, Fabien; Schmittbuhl, Matthieu; Pannetier, Solange; Viriot, Laurent; Hanauer, André; Dollé, Pascal; Bloch-Zupan, Agnès

    2014-01-01

    Background The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked dominant genetic disorder causing mental retardation, skeletal growth delays, with craniofacial and digital abnormalities typically associated with this syndrome. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized. Methodology/Principal Findings We examined, using X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, a model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report Rsk mutation produces surpernumerary teeth midline/mesial to the first molar. This highly penetrant phenotype recapitulates more ancestral tooth structures lost with evolution. Most likely this leads to a reduction of the maxillary diastema. Abnormalities of molar shape were generally restricted to the mesial part of both upper and lower first molars (M1). Expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) was performed at various stages of odontogenesis in wild-type (WT) mice. Rsk2 is expressed in the mesenchymal, neural crest-derived compartment, correlating with proliferative areas of the developing teeth. This is consistent with RSK2 functioning in cell cycle control and growth regulation, functions potentially responsible for severe dental phenotypes. To uncover molecular pathways involved in the etiology of these defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars. We further demonstrated a misregulation of several critical genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro. Conclusions This study reveals RSK2 regulates craniofacial development including tooth development and patterning via novel transcriptional targets. PMID:24416220

  5. 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

  6. [Human skull development and voice disorders].

    PubMed

    Piron, A; Roch, J B

    2006-01-01

    The hominisation of the skull comes with the bipedic posture, due to a network of muscular and aponevrotic forces applied to the cranio-facial skeleton. A brief sight of the morphogenetic origine and issues of these forces help to understand more clearly the postural statement of the larynx, his functions, and his many extrinsic biomechanical bounds; then further his most frequently dysfunctions. The larynx is surrounded by several effective systems of protection: active, activo-passive, passive. The architectural features of the components of the laryngeal system allows us to consider the laryngeal function as an auto-balanced system. All the forces engaged are auto-balanced in a continuum of tension. This lead us to the concept of tensegrity system, neologism coming from tensional integrity described by Buckminster Fuller. The laryngeal employement by extrinsic system is pathological in case of chronicity. Any osteopathic treatment, which aims to restore the losses of laryngeal mobility, has to release first the peripherical structures involved in the laryngeal defense, before normalising the larynx itself Finally, the larynx recovers his functions in a tensegrity system.

  7. 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

  8. Common mechanisms in development and disease: BMP signaling in craniofacial development

    PubMed Central

    Graf, Daniel; Malik, Zeba; Hayano, Satoru; Mishina, Yuji

    2015-01-01

    BMP signaling is one of the key pathways regulating craniofacial development. It is involved in the early pattering of the head, the development of cranial neural crest cells, and facial patterning. It regulates development of its mineralized structures, such as cranial bones, maxilla, mandible, palate, and teeth. Targeted mutations in the mouse have been instrumental to delineate the functional involvement of this signaling network in different aspects of craniofacial development. Gene polymorphisms and mutations in BMP pathway genes have been associated with various non-syndromic and syndromic human craniofacial malformations. The identification of intricate cellular interactions and underlying molecular pathways illustrate the importance of local fine-regulation of Bmp signaling to control proliferation, apoptosis, epithelial-mesenchymal interactions, and stem/progenitor differentiation during craniofacial development. Thus, BMP signaling contributes both to shape and functionality of our facial features. BMP signaling also regulates postnatal craniofacial growth and is associated with dental structures life-long. A more detailed understanding of BMP function in growth, homeostasis, and repair of postnatal craniofacial tissues will contribute to our ability to rationally manipulate this signaling network in the context of tissue engineering. PMID:26747371

  9. 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

  10. Surgical options for complex craniofacial pain.

    PubMed

    Sharma, Mayur; Shaw, Andrew; Deogaonkar, Milind

    2014-10-01

    Complex craniofacial pain can be a challenging condition to manage both medically and surgically, but there is a resurgence of interest in the role of neurostimulation therapy. Surgical options for complex craniofacial pain syndromes include peripheral nerve/field stimulation, ganglion stimulation, spinal cord stimulation, dorsal nerve root entry zone lesioning, motor cortex stimulation, and deep brain stimulation. Peripheral nerve/field stimulation is rapidly being explored and is preferred by both patients and surgeons. Technological advances and improved understanding of the interactions of pain pathways with its affective component will widen the scope of neurostimulation therapy for craniofacial pain syndromes.

  11. Augmentation of craniofacial defects using alloplastic material.

    PubMed

    Osunde, O D; Adebola, R A; Ver-or, N; Amole, I O; Akhiwu, B I; Jinjiri, N; Ladeinde, A; Ajike, S O; Efunkoya, A

    2013-09-01

    Alloplastic materials are increasingly being used in augmentation of craniofacial defects because of its ready availability, good aesthetic outcome and absence of donor site morbidity. This paper highlights experience in the use of heat-cured acrylic in augmentation cranioplasty. The management of three patients with anterior skull defect who presented at the Dental and Maxillofacial Surgery Clinic of the Aminu Kano Teaching Hospital over a five-year period is presented. There was good aesthetic outcome in all the patients and no complications were recorded. Augmentation of craniofacial defects using customized prefabricated heat-cured acrylic provides patients with a durable, stable and structural repair of craniofacial defects with good aesthetic outcome.

  12. Core issues in craniofacial myogenesis

    SciTech Connect

    Kelly, Robert G.

    2010-11-01

    Branchiomeric craniofacial muscles control feeding, breathing and facial expression. These muscles differ on multiple counts from all other skeletal muscles and originate in a progenitor cell population in pharyngeal mesoderm characterized by a common genetic program with an adjacent population of cardiac progenitor cells, the second heart field, that gives rise to much of the heart. The transcription factors and signaling molecules that trigger the myogenic program at sites of branchiomeric muscle formation are correspondingly distinct from those in somite-derived muscle progenitor cells. Here new insights into the regulatory hierarchies controlling branchiomeric myogenesis are discussed. Differences in embryological origin are reflected in the lineage, transcriptional program and proliferative and differentiation properties of branchiomeric muscle satellite cells. These recent findings have important implications for our understanding of the diverse myogenic strategies operative both in the embryo and adult and are of direct biomedical relevance to deciphering the mechanisms underlying the cause and progression of muscle restricted myopathies.

  13. Working with DICOM craniofacial images

    PubMed Central

    Grauer, Dan; Cevidanes, Lucia S. H.; Proffit, William R.

    2009-01-01

    The increasing use of cone-beam computed tomography (CBCT) requires changes in our diagnosis and treatment planning methods as well as additional training. The standard for digital computed tomography images is called digital imaging and communications in medicine (DICOM). In this article we discuss the following concepts: visualization of CBCT images in orthodontics, measurement in CBCT images, creation of 2-dimensional radiographs from DICOM files, segmentation engines and multimodal images, registration and superimposition of 3-dimensional (3D) images, special applications for quantitative analysis, and 3D surgical prediction. CBCT manufacturers and software companies are continually working to improve their products to help clinicians diagnose and plan treatment using 3D craniofacial images. PMID:19732681

  14. Osteodistraction in the craniofacial region.

    PubMed

    Bertelè, G; Mercanti, M; Stella, F; Albanese, M; De Santis, D

    2005-04-01

    In the specific field of maxillofacial surgery, the use of osseous distraction is always more and more helpful not only in the rehabilitation of malformation pathologies, but also in the clinical situations that require bone deficit correction resulting from traumatic events and postsurgical effects, for example oncologic surgery. The reason for this versatility in the distraction protocols is, undoubtedly, due to the fact that, at present, they are valid surgical methods in alternative to or supporting maxillofacial surgery, since they are feasible from a very early age and they obtain a level of distraction that is often higher than with orthopedic devices or conventional surgery. There are multiple indications for osteodistraction and they range from cases of hyper- or hypodevelopment of the maxilla and mandible, of both their anteroposterior and transverse components, to complex syndromes such as cleft lip and palate. Even the clinical distraction of the upper and middle thirds of the cranium, through a coronal craniotomy, has been shown to be a safe surgical procedure and it allows, for example, the successful rehabilitation of adult patients suffering from hemifacial microsomia or craniosynostosis. With the continuous and constant evolution of the integration of osteodistraction principles in the rehabilitation of the craniofacial region, an ever-more effective interdisciplinary relationship between orthodontics and osteodistraction has been seen with growing interest. More often treatment plans are programmed in which the orthodontic and osteodistractive phases are integrated and complete each other, each supporting the other. Scientific and clinical progress achieved in this field in recent years, allows more and more refined therapeutic solutions to be programmed, permitting craniofacial operations and to repair an ankylotic dental arch or reposition osteointegrated implants to the most convenient bone sites.

  15. Fate of implant-retained craniofacial prostheses: life span and aftercare.

    PubMed

    Visser, Anita; Raghoebar, Gerry M; van Oort, Robert P; Vissink, Arjan

    2008-01-01

    To assess the need for surgical and prosthetic aftercare of craniofacial prostheses supported by endosseous implants. A retrospective clinical study assessing the surgical and prosthetic aftercare from implant placement to last visit of follow-up was performed in consecutively treated patients with implant-retained craniofacial prostheses in a department of oral and maxillofacial surgery between 1988 and 2003. Ninety-five patients were rehabilitated with implant-retained craniofacial prostheses. Mean follow-up was 88 months (median, 79 months). Two hundred seventy implants were placed; 153 implants in the mastoid region, 99 in the orbital region, and 18 in the nasal region. The craniofacial defects were due to genetic disorders (24 patients), trauma (12 patients), and ablative tumor surgery (59 patients). In the latter group, 104 implants (33 patients) were placed in irradiated bone. Thirty implants were lost; 8 implants in nonirradiated bone (95.2% overall implant survival rate; mastoid, 95.7%; orbit, 94.1%; nose, 87.5%) and 22 implants in irradiated bone (78.8% overall implant survival rate; mastoid, 86.2%; orbit, 73.8%; nose, 90.0%). Irrespective of the craniofacial defect, on average every 1.5 to 2 years a new facial prosthesis was made, mostly for reasons because of discoloration (31.2%), problems with attachment of the acrylic resin clip carrier to the silicone (25.3%), rupture of the silicone (13.3%), or bad fit (10.9%). Severe skin reactions around implants or beneath prostheses were only observed in the orbital region. Implant-retained craniofacial prostheses are a reliable treatment option for the restoration of craniofacial defects. The need for surgical aftercare was minor, and prosthetic aftercare predominantly consisted of making new prostheses.

  16. Obesity and craniofacial structure as risk factors for obstructive sleep apnoea: impact of ethnicity.

    PubMed

    Sutherland, Kate; Lee, Richard W W; Cistulli, Peter A

    2012-02-01

    OSA is the result of structural and functional abnormalities that promote the repetitive collapse of the upper airway during sleep. This common disorder is estimated to occur in approximately 4% of men and 2% of women, with prevalence studies from North America, Australia, Europe and Asia indicating that occurrence is relatively similar across the globe. Anatomical factors, such as obesity and craniofacial morphology, are key determinants of the predisposition to airway collapse; however, their relative importance for OSA risk likely varies between ethnicities. Direct inter-ethnic studies comparing craniofacial phenotypes in OSA are limited. However, available data suggest that Asian OSA populations primarily display features of craniofacial skeletal restriction, African Americans display more obesity and enlarged upper airway soft tissues, while Caucasians show evidence of both bony and soft tissue abnormalities. Our recent comparison of Chinese and Caucasian OSA patients found for the same degree of OSA severity. Caucasians were more obese, and Chinese had more skeletal restriction. However, the ratio of obesity to craniofacial bony size (or anatomical balance, an important determinant of upper airway volume and OSA risk) was similar between Caucasians and Chinese OSA patients. Ethnicity appears to influence OSA craniofacial phenotype but furthermore the relative contribution of the anatomical factors underlying OSA risk. The skeletal restriction craniofacial phenotype may be particularly vulnerable to increasing obesity rates. Better understanding of craniofacial phenotypes encompassing ethnicity may help improve OSA recognition and treatment; however, further studies are needed to elucidate ethnic differences in OSA anatomical risk factors. © 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.

  17. Computer vision guided virtual craniofacial reconstruction.

    PubMed

    Bhandarkar, Suchendra M; Chowdhury, Ananda S; Tang, Yarong; Yu, Jack C; Tollner, Ernest W

    2007-09-01

    The problem of virtual craniofacial reconstruction from a sequence of computed tomography (CT) images is addressed and is modeled as a rigid surface registration problem. Two different classes of surface matching algorithms, namely the data aligned rigidity constrained exhaustive search (DARCES) algorithm and the iterative closest point (ICP) algorithm are first used in isolation. Since the human bone can be reasonably approximated as a rigid body, 3D rigid surface registration techniques such as the DARCES and ICP algorithms are deemed to be well suited for the purpose of aligning the fractured bone fragments. A synergistic combination of these two algorithms, termed as the hybrid DARCES-ICP algorithm, is proposed. The hybrid algorithm is shown to result in a more accurate mandibular reconstruction when compared to the individual algorithms used in isolation. The proposed scheme for virtual reconstructive surgery would prove to be of tremendous benefit to the operating surgeons as it would allow them to pre-visualize the reconstructed mandible (i.e., the end-product of their work), before performing the actual surgical procedure. Experimental results on both phantom and real (human) patient datasets are presented.

  18. Human Communication and Its Disorders - An Overview.

    ERIC Educational Resources Information Center

    1969

    Communication is defined and the neurological bases of it and its disorders are discussed. The prevalence and costs of communicative disorders are described; current research and financial support for it and for training of investigators are reviewed. Details are then given concerning research on hearing, including the auditory system and its…

  19. Enzyme replacement for craniofacial skeletal defects and craniosynostosis in murine hypophosphatasia.

    PubMed

    Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E

    2015-09-01

    Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl(-/-) mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, vertebral and tooth mineralization defects in Alpl(-/-) mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl(-/-) mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microscopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl(-/-) mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl(-/-) calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Enzyme Replacement for Craniofacial Skeletal Defects and Craniosynostosis in Murine Hypophosphatasia

    PubMed Central

    Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E.

    2015-01-01

    Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl−/− mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, verterbral and tooth mineralization defects in Alpl−/− mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl−/− mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microsocopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl−/− mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl−/− calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. PMID:25959417

  1. CRANIAL NEURAL CREST CELLS ON THE MOVE: THEIR ROLES IN CRANIOFACIAL DEVELOPMENT

    PubMed Central

    Cordero, Dwight R.; Brugmann, Samantha; Chu, Yvonne; Bajpai, Ruchi; Jame, Maryam; Helms, Jill A.

    2010-01-01

    The craniofacial region is assembled through the active migration of cells and the rearrangement and sculpting of facial prominences and pharyngeal arches, which consequently make it particularly susceptible to a large number of birth defects. Genetic, molecular, and cellular processes must be temporally and spatially regulated to culminate in the three-dimension structures of the face. The starting constituent for the majority of skeletal and connective tissues in the face is a pluripotent population of cells, the cranial neural crest cells (NCCs). In this review we discuss the newest scientific findings in the development of the craniofacial complex as related to NCCs. Furthermore, we present recent findings on NCC diseases called neurocristopathies and, in doing so, provide clinicians with new tools for understanding a growing number of craniofacial genetic disorders. PMID:21271641

  2. A Preliminary Classification of Human Functional Sexual Disorders

    ERIC Educational Resources Information Center

    Sharpe, Lawrence; And Others

    1976-01-01

    A preliminary classification is presented for functional human sexual disorders. This system is based on objective behavior and reports of distress. Five categories of sexual disorders are proposed, including the behavioral, psychological and informational components of sexual functioning in the individual and the couple. (Author)

  3. Hematologic disorders associated with human immunodeficiency virus and AIDS.

    PubMed

    Cosby, Cecily D

    2007-01-01

    Nurses encounter patients with human immunodeficiency virus infection at various stages of their infection and in a variety of settings. This article focuses on the most common hematologic disorders associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome, which can precipitate complications and frequently accompany hospitalization. It is important for nurses to have a solid foundation as to the cause of these disorders, their impact on quality of life and outcomes, and management strategies.

  4. Untapped Potential of Disordered Proteins in Current Druggable Human Proteome.

    PubMed

    Hu, Gang; Wu, Zhonghua; Wang, Kui; Uversky, Vladimir N; Kurgan, Lukasz

    2016-01-01

    Current efforts in design and characterization of drugs often rely on the structure of their protein targets. However, a large fraction of proteins lack unique 3-D structures and exist as highly dynamic structural ensembles. These intrinsically disordered proteins are involved in pathogenesis of various human diseases and are highly abundant in eukaryotes. Based on a comprehensive analysis of the current druggable human proteome covering 12 drug classes and 18 major classes of drug targets we show a significant bias toward high structural coverage and low abundance of intrinsic disorder. We review reasons for this bias including widespread use of the structural information in various stages of drug development and characterization process and difficulty with attaining structures for the intrinsically disordered proteins. We also discuss future of intrinsically disordered proteins as drug targets. Given the overall high disorder content of the human proteome and current bias of the druggable human proteome toward structural proteins, it is inevitable that disordered proteins will have to raise up on the list of prospective drug targets. The protein disorder-assisted drug design can draw from current rational drug design techniques and would also need novel approaches that no longer rely on a unique protein structure.

  5. 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.

  6. Distraction Osteogenesis of the Craniofacial Skeleton.

    PubMed

    Yu, Jack C.; Fearon, Jeffrey; Havlik, Robert J.; Buchman, Steve R.; Polley, John W.

    2004-07-01

    LEARNING OBJECTIVES:: After studying this article, the participant should be able to: 1. Review the biomechanical principles and pertinent cellular and molecular biology of distraction osteogenesis of the craniofacial skeleton. 2. Describe the clinical indications and applications of distraction osteogenesis of the craniofacial skeleton. 3. Describe maxillary, mandibular, midface, and calvarial procedures in distraction osteogenesis. 4. Discuss the clinical outcomes and complications of distraction osteogenesis of the craniofacial skeleton.The year 2002 marked the end of the first decade in clinical distraction osteogenesis of the craniofacial skeleton. In this short period, its application has increased exponentially. More than 3000 cases have been performed according to a recent survey, and more than 700 articles have been written on this subject in the MEDLINE database since 1996. It is a powerful surgical tool and enables surgeons to achieve results not previously attainable. Despite all this, distraction osteogenesis is practiced by only a small number of plastic surgeons. This article reviews the biomechanical principles; the pertinent cellular and molecular biology; and the clinical indications, applications, controversies, and complications of distraction osteogenesis of the craniofacial skeleton.

  7. Distraction osteogenesis in craniofacial surgery: a review.

    PubMed

    Tavakoli, K; Stewart, K J; Poole, M D

    1998-01-01

    Distraction osteogenesis is a technique of new bone formation by the gradual separation of bony fragments. The method, although initially developed for limb lengthening, is now being applied in the treatment of craniofacial deformities. A number of principles have been established through careful scientific study to guide clinical practice, such as the ideal rate and rhythm of distraction, the need for periosteal preservation during bone division, a "latent period" of neutral fixation before, and a "consolidation period" after distraction. The technique is being applied in craniofacial surgery particularly for mandibular deformities and offers considerable advantages over previous methods such as osteotomy and inlay bone grafting. Donor site morbidity is avoided, the investing soft tissue envelope is concurrently expanded, and the magnitude of the procedure is less. However, the technique is still in its infancy and requires further modification and refinement before widespread acceptance as a treatment in mainstream craniofacial surgery. Problems with cutaneous scarring and socially undesirable external hardware, particularly in the pediatric population, have led to the emergence of intraoral miniature devices, with the ultimate goal of development of a multiplanar internal autodistractor. Furthermore, many principles well established in leg lengthening, such as the rate and rhythm of distraction, need to be reexamined and the parameters redefined with particular reference to the craniofacial skeleton. Distraction osteogenesis has an expanding role in craniofacial surgery.

  8. 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.

  9. Systematic review: craniocervical posture and craniofacial morphology.

    PubMed

    Gomes, Liliane de C Rosas; Horta, Karla O Carpio; Gonçalves, João Roberto; Santos-Pinto, Ary Dos

    2014-02-01

    The purpose of this study was to investigate the published evidence regarding the association between head and cervical posture and craniofacial morphology. An electronic search was conducted in PubMed, Medline, Embase, Scopus, and Cochrane databases up to 23 March 2012. Abstracts that seemed to correspond with the goals of this review were selected by a consensus between two independent reviewers. The original articles were retrieved and evaluated to ensure they match the inclusion criteria. Only articles that directly compared head and/or cervical posture with craniofacial morphology were included. A total of 84 articles were found of which 12 matched all inclusion criteria. Detailed analysis of the methodology in selected articles revealed quality scores ranging from 'weak' to 'moderate'. Nine articles were cross-sectional studies, whereas only three were longitudinal studies. The findings of selected articles were linked together in order to clarify the evidence on sagittal and vertical craniofacial features as well as growth prediction regarding different postures of the head and neck. On the basis of the data obtained from the literature, significant associations were found between variables concerning head and cervical posture and craniofacial morphology. However, the results of this systematic review suggest that such associations should be carefully interpreted, considering that correlation coefficients found ranged from low to moderate. Moreover, conflicting results were observed regarding some postural variables. Further longitudinal studies are required to elucidate the relationship between the development of craniofacial morphology and functional aspects of head and cervical posture.

  10. Craniofacial Reconstruction Evaluation by Geodesic Network

    PubMed Central

    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. PMID:25214890

  11. Photographic protocol for image acquisition in craniofacial microsomia

    PubMed Central

    2011-01-01

    Craniofacial microsomia (CFM) is a congenital condition associated with orbital, mandibular, ear, nerve, and soft tissue anomalies. We present a standardized, two-dimensional, digital photographic protocol designed to capture the common craniofacial features associated with CFM. PMID:22208766

  12. Craniofacial morphological changes of familial bilateral hypodontia of maxillary premolars.

    PubMed

    Zegan, Georgeta; Mavru, Radu Bogdan; Braha, Elena

    2014-01-01

    The hypodontia of a permanent tooth from a dental group represents a normal evolution in human dentition morphology. Nevertheless, the hypodontia of two teeth within a dental group is a rare developmental anomaly when not associated to a systemic syndrome. The aim of this study was to report two rare cases of four maxillary premolars hypodontia, not including the third molar, of two white women from the same family. There were presented clinical, radiological and genetic findings. These cases are of interest to practitioners for four aspects: the atypical phenotype of hypodontia, the complexity of craniofacial morphological changes, the autosomal dominant familial inheritance with variable expressivity and the difficult classification of diagnosis.

  13. A Reduction in Radiation Exposure During Pediatric Craniofacial Computed Tomography.

    PubMed

    Zarella, Christopher; Didier, Ryne; Bergquist, Curtis; Bardo, Dianna M E; Selden, Nathan R; Kuang, Anna A

    2016-03-01

    Radiation exposure during computed tomography (CT) evaluation in children is the subject of growing professional and public concern. The authors previously demonstrated an 18% reduction in effective radiation dose during craniofacial CT imaging using a modified head position ("exaggerated sniff"), without any compromise of image diagnostic quality. The current study reports additional reduction of radiation exposure using a commercially available iterative reconstruction CT technique. This single-institution, retrospective cohort study compared the overall effective radiation dose received during elective pediatric craniofacial CT imaging. Patients imaged using the iterative reconstruction and exaggerated sniff protocol combined (January 2010 through December 2013) were compared with those undergoing imaging with the exaggerated sniff position alone, between October 2008 and January 2010. A total of 325 patients who underwent CT imaging with the exaggerated sniff position, decreased dose and iterative reconstruction protocol experienced an average effective radiation dose of 1.22 mSv (47% reduction), compared with 2.32 mSv for the sniff-position alone group. Age-matched reference patients not treated using either protocol received an average of 2.82 mSv. This represents a 56.7% average radiation dose reduction for combined sniff position and iterative reconstruction patients compared with reference patients and 47.4% reduction compared with the sniff-position alone group. Image quality of both bone and brain windows was equivalent. Altering head position and use of iterative reconstruction technique with a reduced radiation protocol diminishes CT imaging-related effective radiation dose by approximately 50% in children undergoing elective cranial CT imaging for craniofacial disorders.

  14. Directory: Information Resources for Human Communication Disorders.

    ERIC Educational Resources Information Center

    National Inst. on Deafness and Other Communications Disorders, Bethesda, MD.

    This directory is designed to encourage networking among individuals and organizations that have an interest in deafness and communication disorders. The main body of the directory includes descriptions and publications of 122 organizations that are national in scope and that focus on health issues relating to hearing, balance, smell, taste,…

  15. Craniofacial ontogeny in Centrosaurus apertus.

    PubMed

    Frederickson, Joseph A; Tumarkin-Deratzian, Allison R

    2014-01-01

    Centrosaurus apertus, a large bodied ceratopsid from the Late Cretaceous of North America, is one of the most common fossils recovered from the Belly River Group. This fossil record shows a wide diversity in morphology and size, with specimens ranging from putative juveniles to fully-grown individuals. The goal of this study was to reconstruct the ontogenetic changes that occur in the craniofacial skeleton of C. apertus through a quantitative cladistic analysis. Forty-seven cranial specimens were independently coded in separate data matrices for 80 hypothetical multistate growth characters and 130 hypothetical binary growth characters. Both analyses yielded the max-limit of 100,000 most parsimonious saved trees and the strict consensus collapsed into large polytomies. In order to reduce conflict resulting from missing data, fragmentary individuals were removed and the analyses were rerun. Among both the complete and the reduced data sets the multistate analyses recovered a shorter tree with a higher consistency index (CI) than the additive binary data sets. The arrangement within the trees shows a progression of specimens with a recurved nasal horn in the least mature individuals, followed by specimens with straight nasal horns in relatively more mature individuals, and finally specimens with procurved nasal horns in the most mature individuals. The most mature individuals are further characterized by the reduction of the cranial horn ornamentations in late growth stages, a trait that similarly occurs in the growth of other dinosaurs. Bone textural changes were found to be sufficient proxies for relative maturity in individuals that have not reached adult size. Additionally, frill length is congruent with relative maturity status and makes an acceptable proxy for ontogenetic status, especially in smaller individuals. In adult-sized individuals, the fusion of the epiparietals and episquamosals and the orientation of the nasal horn are the best indicators of relative

  16. Craniofacial ontogeny in Centrosaurus apertus

    PubMed Central

    Tumarkin-Deratzian, Allison R.

    2014-01-01

    Centrosaurus apertus, a large bodied ceratopsid from the Late Cretaceous of North America, is one of the most common fossils recovered from the Belly River Group. This fossil record shows a wide diversity in morphology and size, with specimens ranging from putative juveniles to fully-grown individuals. The goal of this study was to reconstruct the ontogenetic changes that occur in the craniofacial skeleton of C. apertus through a quantitative cladistic analysis. Forty-seven cranial specimens were independently coded in separate data matrices for 80 hypothetical multistate growth characters and 130 hypothetical binary growth characters. Both analyses yielded the max-limit of 100,000 most parsimonious saved trees and the strict consensus collapsed into large polytomies. In order to reduce conflict resulting from missing data, fragmentary individuals were removed and the analyses were rerun. Among both the complete and the reduced data sets the multistate analyses recovered a shorter tree with a higher consistency index (CI) than the additive binary data sets. The arrangement within the trees shows a progression of specimens with a recurved nasal horn in the least mature individuals, followed by specimens with straight nasal horns in relatively more mature individuals, and finally specimens with procurved nasal horns in the most mature individuals. The most mature individuals are further characterized by the reduction of the cranial horn ornamentations in late growth stages, a trait that similarly occurs in the growth of other dinosaurs. Bone textural changes were found to be sufficient proxies for relative maturity in individuals that have not reached adult size. Additionally, frill length is congruent with relative maturity status and makes an acceptable proxy for ontogenetic status, especially in smaller individuals. In adult-sized individuals, the fusion of the epiparietals and episquamosals and the orientation of the nasal horn are the best indicators of relative

  17. Ovine craniofacial malformation: a morphometrical study.

    PubMed

    Eriksen, T; Kuiper, H; Pielmeier, R; Ganter, M; Distl, O; Staszyk, C

    2012-12-01

    Craniofacial malformation in 64 sheep was phenotypically described as mandibular distoclusion. Digital radiographs were examined in order to determine the degree of morphological changes in certain bones of the skull. Therefore, laterolateral standardised digital radiographs were used to determine anatomic reference points. Subsequently, five reference lines were defined and 16 linear and seven angular measurements were determined to describe malformations in the bones of the skull. Statistical analysis revealed a significant shortening of the rostral part of the corpus mandibulae and of the ramus mandibulae. However, the molar part of the mandible remained unchanged. These morphological changes caused premolar and molar malocclusion. No further craniofacial abnormalities, such as an elongation of the maxilla or of the incisive bone, were identified. In conclusion, the phenotypically observed mandibular distoclusion is caused by a shortening of specific parts of the mandible. This form of ovine craniofacial malformation is therefore best described as brachygnathia inferior.

  18. 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.

  19. 76 FR 30373 - National Institute of Dental & Craniofacial Research; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ... Institute of Dental & Craniofacial Research; Meeting Notice of Closed Meeting Pursuant to section 10(d) of... Institute of Dental and Craniofacial Research Special Emphasis Panel; Review of NIDCR R03 Applications. Date..., National Institute of Dental and Craniofacial Research, 6701 Democracy Blvd., Rm. 676, Bethesda, MD 20892...

  20. Making headway: the roles of Hox genes and neural crest cells in craniofacial development.

    PubMed

    Trainor, Paul A

    2003-04-14

    Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

  1. PUF60 variants cause a syndrome of ID, short stature, microcephaly, coloboma, craniofacial, cardiac, renal and spinal features.

    PubMed

    Low, Karen J; Ansari, Morad; Abou Jamra, Rami; Clarke, Angus; El Chehadeh, Salima; FitzPatrick, David R; Greenslade, Mark; Henderson, Alex; Hurst, Jane; Keller, Kory; Kuentz, Paul; Prescott, Trine; Roessler, Franziska; Selmer, Kaja K; Schneider, Michael C; Stewart, Fiona; Tatton-Brown, Katrina; Thevenon, Julien; Vigeland, Magnus D; Vogt, Julie; Willems, Marjolaine; Zonana, Jonathan; Study, D D D; Smithson, Sarah F

    2017-03-22

    PUF60 encodes a nucleic acid-binding protein, a component of multimeric complexes regulating RNA splicing and transcription. In 2013, patients with microdeletions of chromosome 8q24.3 including PUF60 were found to have developmental delay, microcephaly, craniofacial, renal and cardiac defects. Very similar phenotypes have been described in six patients with variants in PUF60, suggesting that it underlies the syndrome. We report 12 additional patients with PUF60 variants who were ascertained using exome sequencing: six through the Deciphering Developmental Disorders Study and six through similar projects. Detailed phenotypic analysis of all patients was undertaken. All 12 patients had de novo heterozygous PUF60 variants on exome analysis, each confirmed by Sanger sequencing: four frameshift variants resulting in premature stop codons, three missense variants that clustered within the RNA recognition motif of PUF60 and five essential splice-site (ESS) variant. Analysis of cDNA from a fibroblast cell line derived from one of the patients with an ESS variants revealed aberrant splicing. The consistent feature was developmental delay and most patients had short stature. The phenotypic variability was striking; however, we observed similarities including spinal segmentation anomalies, congenital heart disease, ocular colobomata, hand anomalies and (in two patients) unilateral renal agenesis/horseshoe kidney. Characteristic facial features included micrognathia, a thin upper lip and long philtrum, narrow almond-shaped palpebral fissures, synophrys, flared eyebrows and facial hypertrichosis. Heterozygote loss-of-function variants in PUF60 cause a phenotype comprising growth/developmental delay and craniofacial, cardiac, renal, ocular and spinal anomalies, adding to disorders of human development resulting from aberrant RNA processing/spliceosomal function.European Journal of Human Genetics advance online publication, 22 March 2017; doi:10.1038/ejhg.2017.27.

  2. Dental Approach to Craniofacial Syndromes: How Can Developmental Fields Show Us a New Way to Understand Pathogenesis?

    PubMed Central

    Kjær, Inger

    2012-01-01

    The paper consists of three parts. Part 1: Definition of Syndromes. Focus is given to craniofacial syndromes in which abnormal traits in the dentition are associated symptoms. In the last decade, research has concentrated on phenotype, genotype, growth, development, function, and treatment. Part 2: Syndromes before Birth. How can the initial malformation sites in these syndromes be studied and what can we learn from it? In this section, deviations observed in syndromes prenatally will be highlighted and compared to the normal human embryological craniofacial development. Specific focus will be given to developmental fields studied on animal tissue and transferred to human cranial development. Part 3: Developmental Fields Affected in Two Craniofacial Syndromes. Analysis of primary and permanent dentitions can determine whether a syndrome affects a single craniofacial field or several fields. This distinction is essential for insight into craniofacial syndromes. The dentition, thus, becomes central in diagnostics and evaluation of the pathogenesis. Developmental fields can explore and advance the concept of dental approaches to craniofacial syndromes. Discussion. As deviations in teeth persist and do not reorganize during growth and development, the dentition is considered useful for distinguishing between syndrome pathogenesis manifested in a single developmental field and in several fields. PMID:23091490

  3. Growth Hormone and Craniofacial Tissues. An update

    PubMed Central

    Litsas, George

    2015-01-01

    Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

  4. 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

  5. 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

  6. Shining evolutionary light on human sleep and sleep disorders

    PubMed Central

    Nunn, Charles L.; Samson, David R.; Krystal, Andrew D.

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep—i.e. ‘why’ sleep evolved—remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or ‘nest’. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. PMID:27470330

  7. 76 FR 57748 - National Institute of Dental & Craniofacial Research Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-16

    ... From the Federal Register Online via the Government Publishing Office 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...

  8. 77 FR 50140 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-20

    ... From the Federal Register Online via the Government Publishing Office 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...

  9. 76 FR 79199 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-21

    ... From the Federal Register Online via the Government Publishing Office 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...

  10. 78 FR 65345 - National Institute of Dental & Craniofacial Research; Amended Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... From the Federal Register Online via the Government Publishing Office 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 NIDCR Special Grants...

  11. 77 FR 29673 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... [Federal Register Volume 77, Number 97 (Friday, May 18, 2012)] [Notices] [Page 29673] [FR Doc No: 2012-12009] 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...

  12. 75 FR 67381 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental and 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...

  13. 77 FR 35988 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental and 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...

  14. 75 FR 28028 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental and 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...

  15. 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.

  16. 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

  17. The comparative psychopathology of affective disorders in animals and humans.

    PubMed

    Healy, D

    1987-01-01

    Reviews of animal models of affective disorders commonly concentrate on the behavioural features thereof, the supposed neurochemical substrates, the mode of production and the response to treatment of the state in question but ignore questions of psycho pathology. An attempt is made to deal critically with the psychopathology of human and animal affective disorders in the light of current operational criteria for the diagnosis of major depressive disorders. It is argued thatthe psychopathological tradition stemming from Jaspers may be more appropriate to a consideration of animal models of affective disorders than the psychopathological positions implicit in psychoanalysis, behaviourism or current cognitive psychologies and in addition more suited to meet these criteria. The adoption of such a perspective results in a shift of emphasis from abnormalities of psychological content to demonstrable neuropsychological deficits and a definition of affective disorders, whether in animals or humans, as psychosomatic illnesses, possibly involving a pathology of circadian rhythmicity. This perspective also suggests that animal models may be useful in the devel opment of more refined diagnostic criteria for affective disorders in humans.

  18. Psychosocial adjustment and craniofacial malformations in childhood.

    PubMed

    Pertschuk, M J; Whitaker, L A

    1985-02-01

    Forty-three children between the ages of 6 and 13 years with congenital facial anomalies underwent psychosocial evaluation prior to surgery. Also evaluated were healthy children matched to the craniofacial subjects by sex, age, intelligence, and economic background. Relative to this comparison group, the craniofacial children were found to have poorer self-concept, greater anxiety at the time of evaluation, and more introversion. Parents of the craniofacial children noted more frequent negative social encounters for their children and more hyperactive behavior at home. Teachers reported more problematic classroom behavior. Examination of these results revealed craniofacial malformations to be associated with psychosocial limitations rather than marked deficits. These children tended to function less well than the comparison children, but with few exceptions, they were not functioning in a psychosocially deviant range. Explanations for the observed circumscribed impact of facial deformity include the use of denial as a coping mechanism, possible diminished significance of appearance for younger children, and the restricted environment experienced by most of the subjects. It can be predicted that time would render these protective influences ineffective, so that adolescent and young adult patients could be at far greater psychosocial risk.

  19. 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...

  20. Association between overbite and craniofacial growth pattern.

    PubMed

    Claro, Cristiane Aparecida de Assis; Abrão, Jorge; Reis, Silvia Augusta Braga

    2010-01-01

    The purpose of the present study was to assess the association between overbite and craniofacial growth pattern. The sample comprised eighty-six cephalograms obtained during the orthodontic pretreatment phase and analyzed using the Radiocef program to identify the craniofacial landmarks and perform orthodontic measurements. The variables utilized were overbite, the Jarabak percentage and the Vert index, as well as classifications resulting from the interpretation of these measurements. In all the statistical tests, a significance level of 5% was considered. Measurement reliability was checked by calculating method error. Weighted Kappa analysis showed that agreement between the facial types defined by the Vert index and the direction of growth trend established by the Jarabak percentage was not satisfactory. Owing to this lack of equivalency, a potential association between overbite and craniofacial growth pattern was evaluated using the chi-square test, considering the two methods separately. No relationship of dependence between overbite and craniofacial growth pattern was revealed by the results obtained. Therefore, it can be concluded that the classification of facial growth pattern will not be the same when considering the Jarabak and the Ricketts anayses, and that increased overbite cannot be associated with a braquifacial growth pattern, nor can openbite be associated with a dolichofacial growth pattern.

  1. 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...

  2. 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…

  3. 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…

  4. A new autosomal dominant craniofacial deafness syndrome.

    PubMed

    Kassutto, S; Kassutto, Z; Ben-Ami, T; Goodman, R M

    1987-11-01

    A Jewish family is reported in which the proband and her father had congenital hearing loss and unusual facies consisting of facial asymmetry, temporal alopecia with frontal bossing, a broad nasal root and small nasal alae. In addition, both were born with a short frenulum of the tongue. We believe these findings represent a new autosomal dominant deafness syndrome with distinct craniofacial features.

  5. Discrimination among adults with craniofacial conditions.

    PubMed

    Roberts, Rachel M

    2014-01-01

    The primary goal of this study was to establish the level of perceived discrimination experienced by adults with congenital craniofacial conditions in Australia and to examine predictors of discrimination. Specifically, this study tested whether social support mediates the relationship between discrimination and health. Adults (n = 93) who had been treated at the Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide for congenital craniofacial conditions (not including cleft lip and/or palate) completed questionnaires examining satisfaction with life, quality of life, anxiety and depression, self-esteem, satisfaction with social support, and satisfaction with appearance. A substantial minority of adults with congenital craniofacial conditions reported that they experience discrimination almost every day in a range of areas. Higher reports of discrimination were related to older age, being male, and less education. Other factors related to higher discrimination included lower levels of satisfaction with life, self-esteem, satisfaction with appearance and mental quality of life, as well as higher levels of anxiety and depression. Social support partially mediated the relationship between discrimination and mental health outcomes. The current study shows that discrimination experiences continue into adulthood confirming the importance of ensuring patients are well supported both by psychosocial services as well as within their own social support networks.

  6. Injectable Biomaterials for Regenerating Complex Craniofacial Tissues**

    PubMed Central

    Kretlow, James D.; Young, Simon; Klouda, Leda; Wong, Mark; Mikos, Antonios G.

    2009-01-01

    Engineering complex tissues requires a precisely formulated combination of cells, spatiotemporally released bioactive factors, and a specialized scaffold support system. Injectable materials, particularly those delivered in aqueous solution, are considered ideal delivery vehicles for cells and bioactive factors and can also be delivered through minimally invasive methods and fill complex 3D shapes. In this review, we examine injectable materials that form scaffolds or networks capable of both replacing tissue function early after delivery and supporting tissue regeneration over a time period of weeks to months. The use of these materials for tissue engineering within the craniofacial complex is challenging but ideal as many highly specialized and functional tissues reside within a small volume in the craniofacial structures and the need for minimally invasive interventions is desirable due to aesthetic considerations. Current biomaterials and strategies used to treat craniofacial defects are examined, followed by a review of craniofacial tissue engineering, and finally an examination of current technologies used for injectable scaffold development and drug and cell delivery using these materials. PMID:19750143

  7. Reciprocal influence of masticatory apparatus, craniofacial structure and whole body homeostasis.

    PubMed

    Lee, Yong-Keun; Moon, Hyung-Joo

    2012-12-01

    There are evidences that the evolution into Homo erectus was partially induced by masticatory muscular dystrophy caused by a gene mutation, which in turn increased brain capacity and led to bipedalism. It is generally accepted that the morphology and function of mammalian skull are partially controlled by epigenetic mechanisms. Archeologic evidences support that the masticatory apparatus have influenced the mechanical stress distribution in hominin skull, and consequently changed craniofacial morphology and function. Even after evolution into H. erectus, alterations in food properties by civilization and cultural preferences have caused modification of human masticatory pattern and accordingly craniofacial structure. Since there are evidences that prehuman and human masticatory apparatus has been influenced the craniofacial and whole body morphology and function, this apparatus in turn might influence whole body homeostasis. Plausible reciprocal influencing mechanisms of the masticatory apparatus on the whole body homeostasis might be (1) direct mechanical influence on the craniofacial structure, (2) distortion of cerebrospinal fluid circulation, and/or (3) several neural/humoral routes. Based on these backgrounds, the hypothesis of the present study is that the morphology and function of masticatory apparatus influence the whole body homeostasis and these interactions are reciprocal. Therefore, human masticatory apparatus, at the present time, should be kept in its physiological status to maintain the whole body homeostasis. We recommend basic and clinical approaches to confirm this hypothesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. The FaceBase Consortium: a comprehensive resource for craniofacial researchers.

    PubMed

    Brinkley, James F; Fisher, Shannon; Harris, Matthew P; Holmes, Greg; Hooper, Joan E; Jabs, Ethylin Wang; 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; Chai, Yang

    2016-07-15

    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.

  9. 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

  10. Homozygous frameshift mutation in TMCO1 causes a syndrome with craniofacial dysmorphism, skeletal anomalies, and mental retardation

    PubMed Central

    Xin, Baozhong; Puffenberger, Erik G.; Turben, Susan; Tan, Haiyan; Zhou, Aimin; Wang, Heng

    2009-01-01

    We identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. The typical craniofacial dysmorphism included brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represented skeletal anomalies. The genome-wide homozygosity mapping using six affected individuals localized the disease gene to a 3.3-Mb region on chromosome 1q23.3-q24.1. Candidate gene sequencing identified a homozygous frameshift mutation, c.139_140delAG, in the transmembrane and coiled-coil domains 1 (TMCO1) gene, as the pathogenic change in all affected members of the extended pedigree. This mutation is predicted to result in a severely truncated protein (p.Ser47Ter) of only one-fourth the original length. The TMCO1 gene product is a member of DUF841 superfamily of several eukaryotic proteins with unknown function. The gene has highly conserved amino acid sequence and is universally expressed in all human tissues examined. The high degree of conservation and the ubiquitous expression pattern in human adult and fetal tissues suggest a critical role for TMCO1. This report shows a TMCO1 sequence variant being associated with a genetic disorder in human. We propose “TMCO1 defect syndrome” as the name of this condition. PMID:20018682

  11. SEARCHING HUMAN BRAIN FOR MECHANISMS OF PSYCHIATRIC DISORDERS

    PubMed Central

    Berretta, Sabina; Heckers, Stephan; Benes, Francine M.

    2014-01-01

    In the past 25 years, research on the human brain has been providing a clear path toward understanding the pathophysiology of psychiatric illnesses. The successes that have been accrued are matched by significant difficulties identifying and controlling a large number of potential confounding variables. By systematically and effectively accounting for unwanted variance in data from imaging and postmortem human brain studies, meaningful and reliable information regarding the pathophysiology of human brain disorders can be obtained. This perspective paper focuses on postmortem investigations to discuss some of the most challenging sources of variance, including diagnosis, comorbidity, substance abuse and pharmacological treatment, which confound investigations of human brain. PMID:25458567

  12. The future of research in craniofacial biology and what this will mean for oral health professional education and clinical practice.

    PubMed

    Slavkin, H C

    2014-06-01

    Today, and looking to the future, scientific discoveries from cellular, developmental and molecular biology inform our understanding of cell, tissue and organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel, muscle, nerve and many organs such as salivary glands and teeth. Present day biomedical science yields principles for the biomimetic design and fabrication of cells, tissues and organs. Bioengineering has become a strategy that can 'mimic' biological processes, and inform clinical procedures for tissue and organ replacements. The future of regenerative craniofacial biology holds enormous promise for the diagnosis and treatment of congenital birth defects, traumatic injuries, degenerative chronic diseases as well as for Mendelian single gene and complex multigene diseases and disorders. The past 50 years have heralded the completion of the human genome and the introduction of 'personalized medicine and dentistry', the utilization of stem cell therapy for an array of diseases and disorders, the 'proof of principle' to reverse select inherited diseases such as anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary research drawn from the diverse biomedical sciences. Looking to the future, we can readily anticipate as major goals to emphasize the clinician's role in identifying clinical phenotypes that can lead to differential diagnosis, and rejuvenate missing or damaged tissues by establishing processes for the utilization of gene, cell and/or protein therapies. The future is replete with remarkable opportunities to enhance clinical outcomes for congenital as well as acquired craniofacial malformations. Clinicians play a pivotal role because critical thinking and sound clinical acumen substantially improve diagnostic precision and thereby clinical health outcomes.

  13. Antioxidant therapy in human endocrine disorders.

    PubMed

    Golbidi, Saeid; Laher, Ismail

    2010-01-01

    Reactive oxygen species (ROS) have deleterious or beneficial effects; this dual nature of ROS means that ROS act as intracellular signaling molecules and as defense mechanisms against micro-organisms. An overproduction of ROS results in oxidative stress, a deleterious process that damages cell structures, including lipids, proteins, and DNA. Oxidative stress plays a major role in various human disease states, including endocrine dysfunction. As a safeguard against oxidative stress, several endogenous nonenzymatic and enzymatic antioxidant systems exist. Antioxidants can delay or prevent oxidative stress and are widely used in the hope of maintaining health and preventing diseases. Although early studies suggested that antioxidant supplements promoted health, later clinical trials revealed that it may not be true in all cases. In this article, we provide a brief review of the pathophysiologic aspects of oxidative stress in a number of the most commonly human endocrionopathies (diabetes, male and female infertility and thyroid diseases) and review the therapeutic potentials of existing antioxidant strategies. We focus on human clinical trials and discuss the implications of their results. Based on the data reported so far, we conclude that the results reported challenge us to design better antioxidant trials in future, with a particular emphasis on identifying 1) appropriate doses 2) selecting the right populations 3) treating for optimal durations and 4) specific intracellular targeting mechanisms.

  14. Human GRIN2B variants in neurodevelopmental disorders

    PubMed Central

    Hu, Chun; Chen, Wenjuan; Myers, Scott J.; Yuan, Hongjie; Traynelis, Stephen F.

    2016-01-01

    The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-D-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies. PMID:27818011

  15. The etiology and molecular genetics of human pigmentation disorders.

    PubMed

    Baxter, Laura L; Pavan, William J

    2013-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically, normal human pigmentation encompasses a variety of skin and hair color as well as punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions in different cell types. Thus, unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, arising from a common developmental origin and/or shared genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities are instructive for understanding normal pathways governing development and function of melanocytes. Copyright © 2012 Wiley Periodicals, Inc.

  16. The etiology and molecular genetics of human pigmentation disorders

    PubMed Central

    Baxter, Laura L.; Pavan, William J.

    2012-01-01

    Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically normal human pigmentation encompasses a variety of skin and hair color as well as with punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while clinically abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions, often in different cell types. Thus unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, revealing a common cellular origin and/or common genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities is instructive for understanding normal pathways governing development and function of melanocytes. PMID:23799582

  17. The emerging roles of ribosome biogenesis in craniofacial development

    PubMed Central

    Ross, Adam P.; Zarbalis, Konstantinos S.

    2014-01-01

    Neural crest cells (NCCs) are a transient, migratory cell population, which originates during neurulation at the neural folds and contributes to the majority of tissues, including the mesenchymal structures of the craniofacial skeleton. The deregulation of the complex developmental processes that guide migration, proliferation, and differentiation of NCCs may result in a wide range of pathological conditions grouped together as neurocristopathies. Recently, due to their multipotent properties neural crest stem cells have received considerable attention as a possible source for stem cell based regenerative therapies. This exciting prospect underlines the need to further explore the developmental programs that guide NCC differentiation. This review explores the particular importance of ribosome biogenesis defects in this context since a specific interface between ribosomopathies and neurocristopathies exists as evidenced by disorders such as Treacher-Collins-Franceschetti syndrome (TCS) and Diamond-Blackfan anemia (DBA). PMID:24550838

  18. Anterior throat pain syndromes: causes for undiagnosed craniofacial pain.

    PubMed

    Shankland, Wesley E

    2010-01-01

    It is not uncommon for practitioners who treat craniofacial pain to see patients with undiagnosed throat and submandibular pain. Usually, these patients will already have been seen by their primary care physician and frequently, several others doctors including otolaryngologists, oral and maxillofacial surgeons, and even neurologists. Far too often these patients have three common features: 1. they have endured multiple expensive diagnostic tests; 2. they have received treatment of multiple courses of antibiotics; and 3. no specific diagnosis for their pain complaints has been determined and their pain persists. In this article, five disorders, Ernest syndrome, Eagle's syndrome, carotid artery syndrome, hyoid bone syndrome and superior pharyngeal constrictor syndrome are briefly described. All five produce common symptoms, making diagnosis difficult, which is often followed by ineffective or no treatment being provided to the patient. Diagnostic criteria and suggested treatment modalities are also presented.

  19. 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

  20. Wnt Signaling and Its Contribution to Craniofacial Tissue Homeostasis.

    PubMed

    Yin, X; Li, J; Salmon, B; Huang, L; Lim, W H; Liu, B; Hunter, D J; Ransom, R C; Singh, G; Gillette, M; Zou, S; Helms, J A

    2015-11-01

    A new field of dental medicine seeks to exploit nature's solution for repairing damaged tissues, through the process of regeneration. Most adult mammalian tissues have limited regenerative capacities, but in lower vertebrates, the molecular machinery for regeneration is an elemental part of their genetic makeup. Accumulating data suggest that the molecular pathways responsible for the regenerative capacity of teleosts, amphibians, and reptiles have fallen into disuse in mammals but that they can be "jumpstarted" by the selective activation of key molecules. The Wnt family of secreted proteins constitutes one such critical pathway: Wnt proteins rank among the most potent and ubiquitous stem cell self-renewing factors, with tremendous potential for promoting human tissue regeneration. Wnt reporter and lineage-tracing strains of mice have been employed to create molecular maps of Wnt responsiveness in the craniofacial tissues, and these patterns of Wnt signaling colocalize with stem/progenitor populations in the rodent incisor apex, the dental pulp, the alveolar bone, the periodontal ligament, the cementum, and oral mucosa. The importance of Wnt signaling in both the maintenance and healing of these craniofacial tissues is summarized, and the therapeutic potential of Wnt-based strategies to accelerate healing through activation of endogenous stem cells is highlighted.

  1. Electrospun 3D composite scaffolds for craniofacial critical size defects.

    PubMed

    Chakrapani, V Yogeshwar; Kumar, T S Sampath; Raj, Deepa K; Kumary, T V

    2017-08-01

    Critical size defects in the craniofacial region can be effectively treated using three dimensional (3D) composite structures mimicking natural extra cellular matrix (ECM) and incorporated with bioactive ceramics. In this study we have shown that the dynamic liquid bath collector can be used to form electrospun polycaprolactone (PCL)-hydroxyapatite (HA) composite structure as unique 3D scaffold. The structure was found to have three distinct sections (base, stem and head) based on the mechanism of its formation and morphology. The size of the head portion was around 15 mm and was found to vary with the process parameters. Scanning electron microscopy (SEM) analysis revealed that the base had random fibres while the fibres in stem and head sections were aligned but perpendicular to each other. X-ray diffraction (XRD) analysis also showed an increase in the crystallinity index of the fibres from base to head section. Cytotoxicity and cytocompatibility studies using human osteosarcoma (HOS) cells showed good cell adhesion and proliferation indicating the suitability of the 3D structure for craniofacial graft applications.

  2. The use of craniofacial superimposition for disaster victim identification.

    PubMed

    Wilkinson, Caroline; Lofthouse, Amy

    2015-07-01

    Skull-to-face comparison is utilised for human identification where there is a suspected identity and the usual methods of identification, such as DNA or dental comparison, are not possible or practical. This research aimed to compare the reliability of manual and computerised craniofacial superimposition techniques and to establish the application of these techniques for disaster victim identification, where there may be a large database of passport-style images, such as the MPUB Interpol database. Twenty skulls (10 females; 10 males) were utilised from the William Bass Skeletal Collection at the University of Tennessee and compared to face pools of 20 face photographs of similar sex, age and ethnic group. A traditional manual photographic method and a new 3D computer-based method were used. The results suggested that profile and three-quarter views of the ante-mortem face were the most valuable for craniofacial superimposition. However, the poor identification rate achieved using images in frontal view suggests that the MPUB Interpol database would not be optimal for disaster victim identification, and passport-style images do not provide enough distinguishing facial detail. This suggests that multiple ante-mortem images with a variety of facial expression should be utilised for identification purposes. There was no significant difference in success between the manual and computer methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Reliability of Craniofacial Superimposition Using Three-Dimension Skull Model.

    PubMed

    Gaudio, Daniel; Olivieri, Lara; De Angelis, Danilo; Poppa, Pasquale; Galassi, Andrea; Cattaneo, Cristina

    2016-01-01

    Craniofacial superimposition is a technique potentially useful for the identification of unidentified human remains if a photo of the missing person is available. We have tested the reliability of the 2D-3D computer-aided nonautomatic superimposition techniques. Three-dimension laser scans of five skulls and ten photographs were overlaid with an imaging software. The resulting superimpositions were evaluated using three methods: craniofacial landmarks, morphological features, and a combination of the two. A 3D model of each skull without its mandible was tested for superimposition; we also evaluated whether separating skulls by sex would increase correct identifications. Results show that the landmark method employing the entire skull is the more reliable one (5/5 correct identifications, 40% false positives [FP]), regardless of sex. However, the persistence of a high percentage of FP in all the methods evaluated indicates that these methods are unreliable for positive identification although the landmark-only method could be useful for exclusion. © 2015 American Academy of Forensic Sciences.

  4. Genetics of human isolated hereditary hair loss disorders.

    PubMed

    Basit, S; Khan, S; Ahmad, W

    2015-09-01

    Hereditary hair loss in human is a group of clinically and genetically heterogeneous disorders. It is characterized by sparse to complete absence of hair on the scalp and other parts of the body. In few cases tightly curled twisted wooly hair (WH) on the scalp has been reported as well. The hair loss disorders, including both syndromic and non-syndromic (isolated) forms, segregate either in autosomal dominant or autosomal recessive pattern. To date, seven autosomal dominant and equal numbers of autosomal recessive isolated forms of hair loss disorders have been characterized. Genes responsible for causing most of these disorders have been identified. In this review, we have provided an update on clinical and genetic aspects of isolated hereditary hair loss disorders manifesting with hypotrichosis and/or WHs. Because most of the recessive genes have been mapped using consanguineous families of Pakistani origin, therefore emphasis is given to mutations identified in these families. OMIM nomenclature has been followed to indicate different forms of hair loss disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Functional diversity and structural disorder in the human ubiquitination pathway.

    PubMed

    Bhowmick, Pallab; Pancsa, Rita; Guharoy, Mainak; Tompa, Peter

    2013-01-01

    The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well

  6. Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

    PubMed Central

    Bhowmick, Pallab; Pancsa, Rita; Guharoy, Mainak; Tompa, Peter

    2013-01-01

    The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred – E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well

  7. Understanding Human Glycosylation Disorders: Biochemistry Leads the Charge*

    PubMed Central

    Freeze, Hudson H.

    2013-01-01

    Nearly 70 inherited human glycosylation disorders span a breathtaking clinical spectrum, impacting nearly every organ system and launching a family-driven diagnostic odyssey. Advances in genetics, especially next generation sequencing, propelled discovery of many glycosylation disorders in single and multiple pathways. Interpretation of whole exome sequencing results, insights into pathological mechanisms, and possible therapies will hinge on biochemical analysis of patient-derived materials and animal models. Biochemical diagnostic markers and readouts offer a physiological context to confirm candidate genes. Recent discoveries suggest novel perspectives for textbook biochemistry and novel research opportunities. Basic science and patients are the immediate beneficiaries of this bidirectional collaboration. PMID:23329837

  8. Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development.

    PubMed

    Badri, Mohammed K; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Haruko; Ray, Manas; Scott, Greg; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

    2016-08-01

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3-, and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ∼20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length, and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. Anat Rec, 299:1110-1120, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Ellis van Creveld2 is required for postnatal craniofacial bone development

    PubMed Central

    Badri, Mohammed K.; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Haruko; Ray, Manas; Scott, Greg; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

    2016-01-01

    Ellis-van Creveld (EvC) syndrome is a genetic disorder with mutations in either EVC or EVC2 gene. Previous case studies reported that EvC patients underwent orthodontic treatment, suggesting the presence of craniofacial bone phenotypes. To investigate whether a mutation in EVC2 gene causes a craniofacial bone phenotype, Evc2 knockout (KO) mice were generated and cephalometric analysis was performed. The heads of wild type (WT), heterozygous (Het) and homozygous Evc2 KO mice (1-, 3- and 6-week-old) were prepared and cephalometric analysis based on the selected reference points on lateral X-ray radiographs was performed. The linear and angular bone measurements were then calculated, compared between WT, Het and KO and statistically analyzed at each time point. Our data showed that length of craniofacial bones in KO was significantly lowered by ~20% to that of WT and Het, the growth of certain bones, including nasal bone, palatal length and premaxilla was more affected in KO, and the reduction in these bone length was more significantly enhanced at later postnatal time points (3 and 6 weeks) than early time point (1 week). Furthermore, bone-to-bone relationship to cranial base and cranial vault in KO was remarkably changed, i.e. cranial vault and nasal bone were depressed and premaxilla and mandible were developed in a more ventral direction. Our study was the first to show the cause-effect relationship between Evc2 deficiency and craniofacial defects in EvC syndrome, demonstrating that Evc2 is required for craniofacial bone development and its deficiency leads to specific facial bone growth defect. PMID:27090777

  10. The craniofacial team and the Navajo patient.

    PubMed

    Smoot, E C; Kucan, J O; Cope, J S; Aase, J M

    1988-10-01

    The craniofacial team at the University of New Mexico Medical Center in Albuquerque, New Mexico has treated a large population of Navajo Indians. Team awareness of the Navajo concept of health as man in balance with his environment has resulted in more expedient treatment of the Navajo children. An understanding of Navajo concerns with ghosts, skinwalkers, and rules for orderly living has allowed team members to integrate the family and the Navajo medicine man in caring for the children with craniofacial disease. Special concerns for informed surgical consent and genetic counseling of the Navajo are reviewed. Respect for the traditional Navajo healing ceremonies and special handling of disposed body parts in surgery are required of the health professionals caring for these people.

  11. Regenerative medicine: implications for craniofacial surgery.

    PubMed

    Schantz, Jan-Thorsten; Machens, Hans-Günther; Schilling, Arndt F; Teoh, Swee-Hin

    2012-03-01

    Craniofacial reconstruction of cases with complex anatomy challenges surgeons. The recently emerging field of tissue engineering and regenerative medicine has resulted in a variety of novel therapeutic concepts particularly in the craniofacial area. However, researchers still face significant problems when translating scientific concepts from the bench to the bedside. Reconstruction procedures depend on sustainability, aesthetic outcome, and functionality. Tissue engineering approaches yield powerful tools for long-term satisfying results enabling customized reconstruction and supporting natural healing processes. In conclusion, further advances of tissue-engineered reconstruction need multidisciplinary research to create complex tissue structures and make satisfactory outcomes clinically achievable for most patients. This review highlights clinical advances in the field and gives an overview about current scientific concepts.

  12. The concept of pattern in craniofacial growth.

    PubMed

    Moyers, R E; Bookstein, F L; Guire, K E

    1979-08-01

    1. There are semantic and associated problems with the word pattern in biology, particularly in orthodontics and facial growth. 2. Pattern, as we use the term, is invariance of relationships--"a set of constraints operating to preserve the integration of parts under varying conditions and through time." 3. Craniofacial pattern can be described and quantified by the identification of craniofacial constants, measures that are relatively invariant. 4. Growth is change and is best identified by studying those measures of size and shape that vary most sensitively through time over development stages. 5. The many traditional cephalometric measures that represent well neither pattern nor growth (mixed) are of less clinical utility than either pure pattern indices or growth indices. 6. The analytical and conceptual separation of pattern and growth seems useful in analysis of morphology, analysis of growth, prediction of growth, and clinical treatment planning.

  13. Etiology of craniofacial malformations in mouse models of blepharophimosis, ptosis and epicanthus inversus syndrome.

    PubMed

    Heude, Églantine; Bellessort, Brice; Fontaine, Anastasia; Hamazaki, Manatsu; Treier, Anna-Corina; Treier, Mathias; Levi, Giovanni; Narboux-Nême, Nicolas

    2015-03-15

    Blepharophimosis, ptosis, epicanthus-inversus syndrome (BPES) is an autosomal dominant genetic disorder characterized by narrow palpebral fissures and eyelid levator muscle defects. BPES is often associated to premature ovarian insufficiency (BPES type I). FOXL2, a member of the forkhead transcription factor family, is the only gene known to be mutated in BPES. Foxl2 is essential for maintenance of ovarian identity, but the developmental origin of the facial malformations of BPES remains, so far, unexplained. In this study, we provide the first detailed account of the developmental processes leading to the craniofacial malformations associated to Foxl2. We show that, during development, Foxl2 is expressed both by Cranial Neural Crest Cells (CNCCs) and by Cranial Mesodermal Cells (CMCs), which give rise to skeletal (CNCCs and CMCs) and muscular (CMCs) components of the head. Using mice in which Foxl2 is selectively inactivated in either CNCCs or CMCs, we reveal that expression of Foxl2 in CNCCs is essential for the development of extraocular muscles. Indeed, inactivation of Foxl2 in CMCs has only minor effects on muscle development, whereas its inactivation in CNCCs provokes a severe hypoplasia of the levator palpabrae superioris and of the superior and inferior oblique muscles. We further show that Foxl2 deletion in either CNCCs or CMCs prevents eyelid closure and induces subtle skeletal developmental defects. Our results provide new insights in the complex developmental origin of human BPES and could help to understand the origin of other ocular anomalies associated to this syndrome.

  14. Imaging findings in craniofacial childhood rhabdomyosarcoma

    PubMed Central

    Merks, Johannes H. M.; Saeed, Peerooz; Balm, Alfons J. M.; Bras, Johannes; Pieters, Bradley R.; Adam, Judit A.; van Rijn, Rick R.

    2010-01-01

    Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3–5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed. PMID:20725831

  15. Craniofacial ballpoint pen injury: endoscopic management.

    PubMed

    LaFrentz, J R; Mair, E A; Casler, J D

    2000-02-01

    Penetrating facial injuries are not infrequent. There have been isolated case reports of unusual penetrating craniofacial trauma. We describe an unusual case of a 22-month-old child who suffered an external orbital injury from a ballpoint pen that penetrated the orbit, lamina papyracea, posterior ethmoid sinuses, and sphenoid sinus. Endoscopic sinus surgery was performed to extract the ballpoint pen nib after localization with computed tomography. Careful pediatric endoscopic sinus surgery techniques permitted safe foreign body extraction with minimal morbidity.

  16. Contribution of FGFR1 Variants to Craniofacial Variations in East Asians

    PubMed Central

    Yamaguchi, Tetsutaro; Tomita, Daisuke; Nakawaki, Takatoshi; Kim, Yong-Il; Hikita, Yu; Haga, Shugo; Takahashi, Masahiro; Nadim, Mohamed A.; Kawaguchi, Akira; Isa, Mutsumi; El-Kenany, Walid H.; El-Kadi, Abbadi A.; Park, Soo-Byung; Ishida, Hajime; Maki, Koutaro; Kimura, Ryosuke

    2017-01-01

    FGFR1 plays an important role in the development of the nervous system as well as the regulation of the skeletal development and bone homeostasis. Mutations in FGFR1 genes affect skull development, specifically suture and synchondrosis, resulting in craniosynostosis and facial abnormalities. We examined subjects with normal skull morphology for genetic polymorphisms that might be associated with normal craniofacial variations. Genomic DNA was obtained from 216 Japanese and 227 Korean subjects. Four FGFR1 SNPs, namely, rs881301, rs6996321, rs4647905, and rs13317, were genotyped. These SNPs were tested for association with craniofacial measurements obtained from lateral and posteroanterior cephalometries, in which principle component analysis was performed to compress the data of the craniofacial measurements. We observed that SNPs rs13317 and rs6996321 were correlated with the overall head size and midfacial development, indicating that FGFR1 SNPs played crucial roles in the normal variation of human craniofacial morphology. Subjects with the derived alleles of SNPs rs13317 and rs6996321 had a small face and a facial pattern associated with a retruded midface and relatively wide-set eyes. These facial features were similar to but were milder than those of individuals with Pfeiffer syndrome, which is caused by a dysfunctional mutation in FGFR1. PMID:28129408

  17. Progress in stem cell therapy for major human neurological disorders.

    PubMed

    Martínez-Morales, P L; Revilla, A; Ocaña, I; González, C; Sainz, P; McGuire, D; Liste, I

    2013-10-01

    Human neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, stroke or spinal cord injury are caused by the loss of neurons and glial cells in the brain or spinal cord in the Central Nervous System (CNS). Stem cell technology has become an attractive option to investigate and treat these diseases. Several types of neurons and glial cells have successfully been generated from stem cells, which in some cases, have ameliorated some dysfunctions both in animal models of neurological disorders and in patients at clinical level. Stem cell-based therapies can be beneficial by acting through several mechanisms such as cell replacement, modulation of inflammation and trophic actions. Here we review recent and current remarkable clinical studies involving stem cell-based therapy for AD and stroke and provide an overview of the different types of stem cells available nowadays, their main properties and how they are developing as a possible therapy for neurological disorders.

  18. Airway adequacy, head posture, and craniofacial morphology.

    PubMed

    Solow, B; Siersbaek-Nielsen, S; Greve, E

    1984-09-01

    Previous studies of different samples have demonstrated associations between craniocervical angulation and craniofacial morphology, between airway obstruction by adenoids and craniofacial morphology, and between airway obstruction and craniocervical angulation. A hypothesis to account for the different sets of associations was suggested by Solow and Kreiborg in 1977. In the present study, the three sets of associations were examined in a single group of nonpathologic subjects with no history of airway obstruction. Cephalometric radiographs taken in the natural head position and rhinomanometric recordings were obtained from twenty-four children 7 to 9 years of age. Correlations were calculated between twenty-seven morphologic, eight postural, and two airway variables. A large craniocervical angle was, on the average, seen in connection with small mandibular dimensions, mandibular retrognathism, and a large mandibular inclination. Obstructed nasopharyngeal airways (defined as a small pm-ad 2 radiographic distance and a large nasal respiratory resistance, NRR, determined rhinomanometrically) were, on the average, seen in connection with a large craniocervical angle and with small mandibular dimensions, mandibular retrognathism, a large mandibular inclination, and retroclination of the upper incisors. The observed correlations were in agreement with the predicted pattern of associations between craniofacial morphology, craniocervical angulation, and airway resistance, thus suggesting the simultaneous presence of such associations in the sample of nonpathologic subjects with no history of airway obstruction.

  19. Craniofacial abnormalities among patients with Edwards Syndrome

    PubMed Central

    Rosa, Rafael Fabiano M.; Rosa, Rosana Cardoso M.; Lorenzen, Marina Boff; Zen, Paulo Ricardo G.; Graziadio, Carla; Paskulin, Giorgio Adriano

    2013-01-01

    OBJECTIVE To determine the frequency and types of craniofacial abnormalities observed in patients with trisomy 18 or Edwards syndrome (ES). METHODS This descriptive and retrospective study of a case series included all patients diagnosed with ES in a Clinical Genetics Service of a reference hospital in Southern Brazil from 1975 to 2008. The results of the karyotypic analysis, along with clinical data, were collected from medical records. RESULTS: The sample consisted of 50 patients, of which 66% were female. The median age at first evaluation was 14 days. Regarding the karyotypes, full trisomy of chromosome 18 was the main alteration (90%). Mosaicism was observed in 10%. The main craniofacial abnormalities were: microretrognathia (76%), abnormalities of the ear helix/dysplastic ears (70%), prominent occiput (52%), posteriorly rotated (46%) and low set ears (44%), and short palpebral fissures/blepharophimosis (46%). Other uncommon - but relevant - abnormalities included: microtia (18%), orofacial clefts (12%), preauricular tags (10%), facial palsy (4%), encephalocele (4%), absence of external auditory canal (2%) and asymmetric face (2%). One patient had an initial suspicion of oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome. CONCLUSIONS: Despite the literature description of a characteristic clinical presentation for ES, craniofacial alterations may be variable among these patients. The OAVS findings in this sample are noteworthy. The association of ES with OAVS has been reported once in the literature. PMID:24142310

  20. Nanomaterials for Craniofacial and Dental Tissue Engineering.

    PubMed

    Li, G; Zhou, T; Lin, S; Shi, S; Lin, Y

    2017-07-01

    Tissue engineering shows great potential as a future treatment for the craniofacial and dental defects caused by trauma, tumor, and other diseases. Due to the biomimetic features and excellent physiochemical properties, nanomaterials are of vital importance in promoting cell growth and stimulating tissue regeneration in tissue engineering. For craniofacial and dental tissue engineering, the frequently used nanomaterials include nanoparticles, nanofibers, nanotubes, and nanosheets. Nanofibers are attractive for cell invasion and proliferation because of their resemblance to extracellular matrix and the presence of large pores, and they have been used as scaffolds in bone, cartilage, and tooth regeneration. Nanotubes and nanoparticles improve the mechanical and chemical properties of scaffold, increase cell attachment and migration, and facilitate tissue regeneration. In addition, nanofibers and nanoparticles are also used as a delivery system to carry the bioactive agent in bone and tooth regeneration, have better control of the release speed of agent upon degradation of the matrix, and promote tissue regeneration. Although applications of nanomaterials in tissue engineering remain in their infancy with numerous challenges to face, the current results indicate that nanomaterials have massive potential in craniofacial and dental tissue engineering.

  1. The craniofacial complex in 47,XYY males.

    PubMed

    Grön, M; Pietilä, K; Alvesalo, L

    1997-08-01

    Eight adult, Finnish 47,XYY males were compared with population male and female controls and, in addition, three of them were compared with first-degree male relatives. Linear and angular measurements were made from standardized lateral cephalograms of patients and normal population controls from the "Kvantti" study series. In both comparisons the craniofacial dimensions in 47,XYY males were larger than those in population male and female controls. Their craniofacial proportions and plane angles were similar to those of normal men except for a larger lower facial height with posterior rotation of the mandible and a tendency to bimaxillary protrusion, a longer cranial base and a lesser cranial-base angle. Thus the supernumerary Y chromosomal gene(s) in 47,XYY males may result in larger craniofacial dimensions than in normal males, without substantial effects on dimensional ratios and plane angles. This general metric pattern is similar to that observed in relation to many adult body and head dimensions, and the dental arches and tooth crowns, of 47,XYY males. The foramen magnum in 47,XYY males was smaller in the sagittal plane than that of normal males and females.

  2. Is craniofacial morphology in Apert and Crouzon syndromes the same?

    PubMed

    Kreiborg, S; Cohen, M M

    1998-12-01

    This article reviews previous research on the craniofacial development in Apert and Crouzon syndromes and adds new roentgencephalometric information. It is concluded that craniofacial development in the two syndromes is not the same. Marked differences were found in the calvaria, cranial base, orbit, maxilla, zygoma, incisal occlusion, and soft tissue profile. In general, abnormal craniofacial morphology was more severe in Apert syndrome than in Crouzon syndrome.

  3. Predictors of mental health in adults with congenital craniofacial conditions attending the Australian craniofacial unit.

    PubMed

    Roberts, R M; Mathias, J L

    2013-07-01

    Objective : Adults with craniofacial conditions experience more psychosocial problems than adults in the general population, but little is known about the factors that render a person more or less susceptible to these problems. Guided by research on adults with other conditions that affect appearance, this study examined predictors of psychosocial outcome in adults with craniofacial conditions. Design : Single-sample cross-sectional design. Setting : The Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide, one of the main craniofacial treatment centers in Australia. Participants : Adults (N  =  93; 36.9% of the potential sample) with congenital craniofacial conditions (excluding cleft lip and/or cleft palate) who were treated in the Australian Craniofacial Unit. Main Outcome Measures : All participants completed measures assessing anxiety, depression, and quality of life (Hospital Anxiety and Depression Scale, Short-Form Health Survey) and variables predicted to affect these outcomes (SF-36 Health Survey - Multidimensional Scale of Perceived Social Support, Rosenberg Self-Esteem Scale, Cleft Satisfaction Profile, Brief Fear of Negative Evaluation Scale, Derriford Appearance Scale). Results : Multiple regression analyses revealed that anxiety was predicted by social support, self-esteem, and fear of negative evaluation, while depression was predicted by self-esteem and social support. Physical quality of life was not predicted by any of the measures. Satisfaction with appearance, gender, age, and education were not related to outcome. Conclusions : Interventions designed to increase perceived social support and self-esteem and reduce fear of negative evaluation appear to be indicated and may assist in establishing a causal relationship between these variables.

  4. Ribosomal protein gene mapping and human chromosomal disorders

    SciTech Connect

    Kenmochi, N.; Goodman, N.; Page, D.C.

    1994-09-01

    In Drosophila, the Minute phenotype (reduced body size, diminished viability and fertility, and short, thin bristles) results from heterozygous deficiencies (deletions) at any one of 50 loci scattered about the genome. A handful of these Minute loci have been molecularly characterized, and all have been found to encode ribosomal proteins. Thus, the Minute phenotype appears to result from reduced protein synthetic capacity in flies with one rather than two copies of a given ribosomal protein (rp) gene. We are pursuing the possibility that similar reductions in protein synthetic capacity--again resulting from rp gene deficiencies--might underlie phenotypes associated with certain chromosomal disorders in humans. We and our colleagues have reported findings consistent with a role for RPS4 deficiency in the etiology of certain features of Turner syndrome, a complex human disorder classically associated with an XO karyotype. We are intrigued by the possibility that deficiencies of other human rp genes might cause phenotypic abnormalities similar to those seen in Turner syndrome--just as deficiencies of any of a number of Drosophila rp genes cause the Minute phenotype. We must first learn the chromosomal map position of each of the estimated 83 human rp genes. The task of mapping the functional (intron-containing) rp genes is complicated by the existence of processed pseudogenes elsewhere in the genome. To date, we have assigned (or confirmed the previous assignment of) 38 rp genes to individual human chromosomes by PCR analysis of human-rodent somatic cell hybrids containing subsets of human chromosomes, with all but four chromosomes carrying at least one rp gene. We have also identified more than 100 large-insert human YAC (yeast artificial chromosome) clones that contain individual rp genes. Such screening of YAC libraries will result in precise positioning of the rp genes on the emerging physical map of the human genome.

  5. Translational genetics for diagnosis of human disorders of sex development.

    PubMed

    Baxter, Ruth M; Vilain, Eric

    2013-01-01

    Disorders of sex development (DSDs) are congenital conditions with discrepancies between the chromosomal, gonadal, and phenotypic sex of the individual. Such disorders have historically been difficult to diagnose and cause great stress to patients and their families. Genetic analysis of human samples has been instrumental in elucidating the molecules and pathways involved in the development of the bipotential gonad into a functioning testis or ovary. However, many DSD patients still do not receive a genetic diagnosis. New genetic and genomic technologies are expanding our knowledge of the underlying mechanism of DSDs and opening new avenues for clinical diagnosis. We review the genetic technologies that have elucidated the genes that are well established in sex determination in humans, discuss findings from more recent genomic technologies, and propose a new paradigm for clinical diagnosis of DSDs.

  6. Translational Genetics for Diagnosis of Human Disorders of Sex Development

    PubMed Central

    Baxter, Ruth M.; Vilain, Eric

    2015-01-01

    Disorders of sex development (DSDs) are congenital conditions with discrepancies between the chromosomal, gonadal, and phenotypic sex of the individual. Such disorders have historically been difficult to diagnose and cause great stress to patients and their families. Genetic analysis of human samples has been instrumental in elucidating the molecules and pathways involved in the development of the bipotential gonad into a functioning testis or ovary. However, many DSD patients still do not receive a genetic diagnosis. New genetic and genomic technologies are expanding our knowledge of the underlying mechanism of DSDs and opening new avenues for clinical diagnosis. We review the genetic technologies that have elucidated the genes that are well established in sex determination in humans, discuss findings from more recent genomic technologies, and propose a new paradigm for clinical diagnosis of DSDs. PMID:23875799

  7. Mentally disordered offenders and the European Court of Human Rights.

    PubMed

    Prior, Pauline M

    2007-01-01

    Mentally disordered offenders find themselves at the intersection of the healthcare system and the criminal justice system in most European countries. Decisions on their care often involve lengthy discussions in relation to care versus control in society. In this article, the focus is on one aspect of this debate - that of human rights. An analysis of cases, taken to the European Court of Human Rights by mentally disordered offenders, demonstrates the difficulties inherent in ensuring appropriate care to individuals and safeguards to the public at the same time. The issues raised include the problems raised by indeterminate sentences, the use of detention for preventive purposes, and debates about treatment. The countries represented in this selection of cases are Belgium, Norway, Poland, the Netherlands, Russia and the United Kingdom.

  8. Craniofacial similarity analysis through sparse principal component analysis

    PubMed Central

    Zhao, Junli; Wu, Zhongke; Li, Jinhua; Deng, Qingqiong; Li, Xiaona; Zhou, Mingquan

    2017-01-01

    The computer-aided craniofacial reconstruction (CFR) technique has been widely used in the fields of criminal investigation, archaeology, anthropology and cosmetic surgery. The evaluation of craniofacial reconstruction results is important for improving the effect of craniofacial reconstruction. Here, we used the sparse principal component analysis (SPCA) method to evaluate the similarity between two sets of craniofacial data. Compared with principal component analysis (PCA), SPCA can effectively reduce the dimensionality and simultaneously produce sparse principal components with sparse loadings, thus making it easy to explain the results. The experimental results indicated that the evaluation results of PCA and SPCA are consistent to a large extent. To compare the inconsistent results, we performed a subjective test, which indicated that the result of SPCA is superior to that of PCA. Most importantly, SPCA can not only compare the similarity of two craniofacial datasets but also locate regions of high similarity, which is important for improving the craniofacial reconstruction effect. In addition, the areas or features that are important for craniofacial similarity measurements can be determined from a large amount of data. We conclude that the craniofacial contour is the most important factor in craniofacial similarity evaluation. This conclusion is consistent with the conclusions of psychological experiments on face recognition and our subjective test. The results may provide important guidance for three- or two-dimensional face similarity evaluation, analysis and face recognition. PMID:28640836

  9. Craniofacial similarity analysis through sparse principal component analysis.

    PubMed

    Zhao, Junli; Duan, Fuqing; Pan, Zhenkuan; Wu, Zhongke; Li, Jinhua; Deng, Qingqiong; Li, Xiaona; Zhou, Mingquan

    2017-01-01

    The computer-aided craniofacial reconstruction (CFR) technique has been widely used in the fields of criminal investigation, archaeology, anthropology and cosmetic surgery. The evaluation of craniofacial reconstruction results is important for improving the effect of craniofacial reconstruction. Here, we used the sparse principal component analysis (SPCA) method to evaluate the similarity between two sets of craniofacial data. Compared with principal component analysis (PCA), SPCA can effectively reduce the dimensionality and simultaneously produce sparse principal components with sparse loadings, thus making it easy to explain the results. The experimental results indicated that the evaluation results of PCA and SPCA are consistent to a large extent. To compare the inconsistent results, we performed a subjective test, which indicated that the result of SPCA is superior to that of PCA. Most importantly, SPCA can not only compare the similarity of two craniofacial datasets but also locate regions of high similarity, which is important for improving the craniofacial reconstruction effect. In addition, the areas or features that are important for craniofacial similarity measurements can be determined from a large amount of data. We conclude that the craniofacial contour is the most important factor in craniofacial similarity evaluation. This conclusion is consistent with the conclusions of psychological experiments on face recognition and our subjective test. The results may provide important guidance for three- or two-dimensional face similarity evaluation, analysis and face recognition.

  10. Genetics and molecular basis of human peroxisome biogenesis disorders.

    PubMed

    Waterham, Hans R; Ebberink, Merel S

    2012-09-01

    Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of autosomal recessive disorders comprised of two clinically distinct subtypes: the Zellweger syndrome spectrum (ZSS) disorders and rhizomelic chondrodysplasia punctata (RCDP) type 1. PBDs are caused by defects in any of at least 14 different PEX genes, which encode proteins involved in peroxisome assembly and proliferation. Thirteen of these genes are associated with ZSS disorders. The genetic heterogeneity among PBDs and the inability to predict from the biochemical and clinical phenotype of a patient with ZSS which of the currently known 13 PEX genes is defective, has fostered the development of different strategies to identify the causative gene defects. These include PEX cDNA transfection complementation assays followed by sequencing of the thus identified PEX genes, and a PEX gene screen in which the most frequently mutated exons of the different PEX genes are analyzed. The benefits of DNA testing for PBDs include carrier testing of relatives, early prenatal testing or preimplantation genetic diagnosis in families with a recurrence risk for ZSS disorders, and insight in genotype-phenotype correlations, which may eventually assist to improve patient management. In this review we describe the current status of genetic analysis and the molecular basis of PBDs. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Studies on Aplysia neurons suggest treatments for chronic human disorders.

    PubMed

    Abrams, Thomas W

    2012-09-11

    For decades, the marine snail Aplysia has proven to be a powerful system for analyzing basic neurobiological mechanisms, particularly cellular and molecular mechanisms of neural plasticity. Three new findings on Aplysia may be relevant for the understanding and treatment of chronic human disorders. This research on this simple molluscan nervous system may lead to new therapeutic approaches for spinal cord injury, Fragile X syndrome, and genetic learning deficits more generally.

  12. CT and MR Imaging in a Large Series of Patients with Craniofacial Fibrous Dysplasia

    PubMed Central

    Atalar, Mehmet Haydar; Salk, Ismail; Savas, Recep; Uysal, Ismail Onder; Egilmez, Hulusi

    2015-01-01

    Summary Background In this retrospective review of patients with craniofacial fibrous dysplasia (FD), the clinical and radiological findings of CT and MR scan were analyzed. Material/Methods The study material included 32 patients, at 9 to 68 years of age that were directed for differential diagnostics of several disorders in the head. We recorded CT and MRI data related to the lesion number, location, sidedness, appearance, and sex of the cases with craniofacial FD. Results Of 32 patients involved in this study, 17 had monostotic and 15 had polyostotic involvement pattern. Bones most commonly involved by monostotic involvement in females were, in descending order, mandibular, maxillary, and sphenoid bones, while the sphenoid bone was involved the most in males. Leontiasis ossea was observed in 2 patients. Sclerotic and mixed lesion types were more common in both females and males. In T1- and T2-weighted MRI sequences, hypointensity was more common compared to hyperintensity or heterogeneous intensity. The type of enhancement of lesions was found similar after contrast medium administration. Conclusions In the presence of craniofacial FD during CT or MRI imaging of the head, a detailed description of FD lesions may provide an important clinical benefit by increasing radiological experience during the diagnostics of this rare disorder. PMID:26000068

  13. Patients seeking treatment for craniofacial pain: a retrospective study of 300 patients.

    PubMed

    Shankland, Wesley E

    2008-10-01

    Those engaged in any type of pain practice will encounter patients who have seen many practitioners. This is especially true for clinicians who treat craniofacial pain and temporomandibular disorders. In this retrospective study of 300 patients seeking treatment for various types of craniofacial pain, the average age was 43.05 years. A mean average of 3.92 clinicians was consulted with the range of practitioners being one to 26. The average time of pain was 4.15 years. Most of the subjects (210) were in the age groups 21 years to 60 years old. Females comprised 85.30% of the subjects with a mean average age of 43.43 years; 14.70% were male with a mean average age of 41.02 years.

  14. Extensiometric analysis of strain in craniofacial bones during implant-supported palatal expansion.

    PubMed

    Nelson Elias, Carlos; Jogaib Fernandes, Daniel; Souza Zanivan, Denis; Resende Fonseca, Yuri

    2017-05-25

    Palatal expansion has several orthodontic and orthopedic applications, such as increasing maxillary transverse dimensions and correcting maxillary atresia, oral breathing, and skeletal cross-bites. Little is known about the strain to which craniofacial bones are submitted when a palatal expander is loaded. The objectives of the present work were to propose a new palatal bone-borne titanium device (expansion screw), to determine patterns of strain distribution in craniofacial bones during palatal expansion and to show the clinical results of a new palatal expander supported by implants. For in vitro testing, the palatal expander supported by two commercially pure titanium (cp Ti) implants was inserted parallel to the median palatine suture of four dry adult human skulls. Uniaxial and triaxial strain gauges were attached to craniofacial bones and connected to a signal acquisition system. An expansion screw was turned and strain data were collected during palatal expansion. The results showed that the bone strain distribution in craniofacial bones loaded by the palatal bone-borne titanium device was complex: the strain was tensile in the palatine cortical bone and compressive in pterygopalatine processes, nasal bones, and orbital floor. The maximum compressive strain occurs in the upper portion of the pterygopalatine processes and the strain changes from compressive to tensile in the zygomatic process. The experimental results suggest that the bone strain due to the palatal expander is distributed over all craniofacial bones and that the upper portions of pterygopalatine processes are the main sites of resistance to palatal expansion. The new palatal expander supported by two cp Ti implants proposed was employed on adult patient as an illustrative report, where adequate palatal expansion was achieved. The new protocol proposed was less invasive, risky, painful and costless for the correction of moderate maxillary transverse deficiency. Copyright © 2017. Published by

  15. 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.

  16. Cranio-facial remodeling in domestic dogs is associated with changes in larynx position.

    PubMed

    Plotsky, Kyle; Rendall, Drew; Chase, Kevin; Riede, Tobias

    2016-06-01

    The hyo-laryngeal complex is a multi-segmented structure integrating the oral and pharyngeal cavities and thus a variety of critical functions related to airway control, feeding, and vocal communication. Currently, we lack a complete understanding of how the hyoid complex, and the functions it mediates, can also be affected by changes in surrounding cranio-facial dimensions. Here, we explore these relationships in a breed of domestic dog, the Portuguese Water Dog, which is characterized by strong cranio-facial variation. We used radiographic images of the upper body and head of 55 adult males and 51 adult females to obtain detailed measures of cranio-facial variation and hyoid anatomy. Principal components analysis revealed multiple orthogonal dimensions of cranio-facial variation, some of which were associated with significant differences in larynx position: the larynx occupied a more descended position in individuals with shorter, broader faces than in those with longer, narrower faces. We then tested the possibility that caudal displacement of the larynx in brachycephalic individuals might reflect a degree of tongue crowding resulting from facial shortening and reduction of oral and pharyngeal spaces. A cadaver sample was used to obtain detailed measurements of constituent bones of the hyoid skeleton and of the tongue body, and their relationships to cranio-facial size and shape and overall body size supported the tongue-crowding hypothesis. Considering the presence of descended larynges in numerous mammalian taxa, our findings establish an important precedent for the possibility that laryngeal descent can be initiated, and even sustained, in part in response to remodeling of the face and cranium for selective pressures unrelated to vocal production. These integrated changes could also have been involved in hominin evolution, where the different laryngeal positions in modern humans compared with nonhuman primates have been traditionally linked to the evolution

  17. Biochemical Analysis of Pathogenic Ligand-Dependent FGFR2 Mutations Suggests Distinct Pathophysiological Mechanisms for Craniofacial and Limb Abnormalities in Human Skeletal Disorders

    SciTech Connect

    Ibrahimi,O.; Zhang, F.; Eliseenkova, A.; Itoh, N.; Linhardt, R.; Mohammadi, M.

    2004-01-01

    Gain-of-function missense mutations in FGF receptor 2 (FGFR2) are responsible for a variety of craniosynostosis syndromes including Apert syndrome (AS), Pfeiffer syndrome (PS) and Crouzon syndrome (CS). Unlike the majority of FGFR2 mutations, S252W and P253R AS mutations and a D321A PS mutation retain ligand-dependency and are also associated with severe limb pathology. In addition, a recently identified ligand-dependent S252L/A315S double mutation in FGFR2 was shown to cause syndactyly in the absence of craniosynostosis. Here, we analyze the effect of the canonical AS mutations, the D321A PS mutation and the S252L/A315S double mutation on FGFR2 ligand binding affinity and specificity using surface plasmon resonance. Both AS mutations and the D321A PS mutation, but not the S252L/A315S double mutation, increase the binding affinity of FGFR2c to multiple FGFs expressed in the cranial suture. Additionally, all four pathogenic mutations also violate FGFR2c ligand binding specificity and enable this receptor to bind FGF10. Based on our data, we propose that an increase in mutant FGFR2c binding to multiple FGFs results in craniosynostosis, whereas binding of mutant FGFR2c to FGF10 results in severe limb pathology. Structural and biophysical analysis shows that AS mutations in FGFR2b also enhance and violate FGFR2b ligand binding affinity and specificity, respectively. We suggest that elevated AS mutant FGFR2b signaling may account for the dermatological manifestations of AS.

  18. Human imprinting disorders: Principles, practice, problems and progress.

    PubMed

    Mackay, Deborah J G; Temple, I Karen

    2017-11-01

    Epigenetic regulation orchestrates gene expression with exquisite precision, over a huge dynamic range and across developmental space and time, permitting genomically-homogeneous humans to develop and adapt to their surroundings. Every generation, these epigenetic marks are re-set twice: in the germline, to enable differentiation of sperm and eggs, and at fertilisation, to create the totipotent zygote that then begins growth and differentiation into a new human. A small group of genes evades the second, zygotic wave of epigenetic reprogramming, and these genes retain an epigenetic 'imprint' of the parent from whom they were inherited. Imprinted genes are (as a general rule) expressed from one parental allele only. Some imprinted genes are critical regulators of growth and development, and thus disruption of their normal monoallelic expression causes congenital imprinting disorders, with clinical features impacting growth, development, behaviour and metabolism. Imprinting disorders as a group have characteristics that challenge diagnosis and management, including clinical and molecular heterogeneity, overlapping clinical features, somatic mosaicism, and multi-locus involvement. New insights into the biology and epigenomics of the early embryo offers new clues about the origin and importance of imprinting disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Modeling the genetic basis for human sleep disorders in Drosophila

    PubMed Central

    Freeman, Amanda A.H.; Syed, Sheyum; Sanyal, Subhabrata

    2013-01-01

    Sleep research in Drosophila is not only here to stay, but is making impressive strides towards helping us understand the biological basis for and the purpose of sleep—perhaps one of the most complex and enigmatic of behaviors. Thanks to over a decade of sleep-related studies in flies, more molecular methods are being applied than ever before towards understanding the genetic basis of sleep disorders. The advent of high-throughput technologies that can rapidly interrogate whole genomes, epigenomes and proteomes, has also revolutionized our ability to detect genetic variants that might be causal for a number of sleep disorders. In the coming years, mutational studies in model organisms such as Drosophila will need to be functionally connected to information being generated from these whole-genome approaches in humans. This will necessitate the development of appropriate methods for interpolating data and increased analytical power to synthesize useful network(s) of sleep regulatory pathways—including appropriate discriminatory and predictive capabilities. Ultimately, such networks will also need to be interpreted in the context of fundamental neurobiological substrates for sleep in any given species. In this review, we highlight some emerging approaches, such as network analysis and mathematical modeling of sleep distributions, which can be applied to contemporary sleep research as a first step to achieving these aims. These methodologies should favorably impact not only a mechanistic understanding of sleep, but also future pharmacological intervention strategies to manage and treat sleep disorders in humans. PMID:23802043

  20. Transferrin receptor facilitates TGF-β and BMP signaling activation to control craniofacial morphogenesis

    PubMed Central

    Lei, R; Zhang, K; Liu, K; Shao, X; Ding, Z; Wang, F; Hong, Y; Zhu, M; Li, H; Li, H

    2016-01-01

    The Pierre Robin Sequence (PRS), consisting of cleft palate, glossoptosis and micrognathia, is a common human birth defect. However, how this abnormality occurs remains largely unknown. Here we report that neural crest cell (NCC)-specific knockout of transferrin receptor (Tfrc), a well known transferrin transporter protein, caused micrognathia, cleft palate, severe respiratory distress and inability to suckle in mice, which highly resemble human PRS. Histological and anatomical analysis revealed that the cleft palate is due to the failure of palatal shelves elevation that resulted from a retarded extension of Meckel's cartilage. Interestingly, Tfrc deletion dramatically suppressed both transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling in cranial NCCs-derived mandibular tissues, suggesting that Tfrc may act as a facilitator of these two signaling pathways during craniofacial morphogenesis. Together, our study uncovers an unknown function of Tfrc in craniofacial development and provides novel insight into the etiology of PRS. PMID:27362800

  1. Speech characteristics in a Ugandan child with a rare paramedian craniofacial cleft: a case report.

    PubMed

    Van Lierde, K M; Bettens, K; Luyten, A; De Ley, S; Tungotyo, M; Balumukad, D; Galiwango, G; Bauters, W; Vermeersch, H; Hodges, A

    2013-03-01

    The purpose of this study is to describe the speech characteristics in an English-speaking Ugandan boy of 4.5 years who has a rare paramedian craniofacial cleft (unilateral lip, alveolar, palatal, nasal and maxillary cleft, and associated hypertelorism). Closure of the lip together with the closure of the hard and soft palate (one-stage palatal closure) was performed at the age of 5 months. Objective as well as subjective speech assessment techniques were used. The speech samples were perceptually judged for articulation, intelligibility and nasality. The Nasometer was used for the objective measurement of the nasalance values. The most striking communication problems in this child with the rare craniofacial cleft are an incomplete phonetic inventory, a severely impaired speech intelligibility with the presence of very severe hypernasality, mild nasal emission, phonetic disorders (omission of several consonants, decreased intraoral pressure in explosives, insufficient frication of fricatives and the use of a middorsum palatal stop) and phonological disorders (deletion of initial and final consonants and consonant clusters). The increased objective nasalance values are in agreement with the presence of the audible nasality disorders. The results revealed that several phonetic and phonological articulation disorders together with a decreased speech intelligibility and resonance disorders are present in the child with a rare craniofacial cleft. To what extent a secondary surgery for velopharyngeal insufficiency, combined with speech therapy, will improve speech intelligibility, articulation and resonance characteristics is a subject for further research. The results of such analyses may ultimately serve as a starting point for specific surgical and logopedic treatment that addresses the specific needs of children with rare facial clefts. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Genetics Home Reference: craniofacial-deafness-hand syndrome

    MedlinePlus

    ... narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips. People ... of neural crest cells leads to the impaired growth of craniofacial bones, nerve tissue, and muscles seen in craniofacial-deafness-hand ... Inheritance Pattern This ...

  3. Craniofacial dysmorphology: Studies in honor of Samuel Pruzansky

    SciTech Connect

    Cohen, M.M.; Rollnick, B.R.

    1985-01-01

    This book contains 31 chapters. Some of the chapter titles are: Regional Specification of Cell-Specific Gene Expression During Craniofacial Development; Timing Cleft Palate Closure - Age Should Not Be the Sole Determinant; Excess of Parental Non-Righthandedness in Children with Right-Sided Cleft Lip: A Preliminary Report; and The Application of Roentgencephalometry to the Study of Craniofacial Anomalies.

  4. 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.

  5. The relationship of bruxism with craniofacial pain and symptoms from the masticatory system in the adult population.

    PubMed

    Ciancaglini, R; Gherlone, E F; Radaelli, G

    2001-09-01

    The association of bruxism with craniofacial pain and symptoms of dysfunction of the masticatory system was assessed in a sample of 483 adult subjects, aged 18-75 years and selected from the general population living in the municipality of Segrate, a metropolitan area in northern Italy. Subjects were interviewed by a questionnaire about oral conditions, occurrence of symptoms of masticatory disturbances, craniofacial and neck pain. The overall prevalence of bruxism was 31;4% (95% confidence interval (CI): 27;3-35;5%). At univariate analysis bruxism was significantly associated with craniofacial pain, difficulty in closing the mouth, difficulty in opening the mouth wide or in locking the mouth, temporomandibular joint sounds, pain on movement, a feeling of stiffness or fatigue of the jaws, and neck pain. After adjustment for reciprocal influences and confounding variables, logistic regression analysis disclosed a strong independent association of bruxism with difficulty in closing the mouth (adjusted odds ratio, (OR): 2;84, 95% CI: 1;68-4;48), and a weaker relationship with craniofacial pain (adjusted OR: 1;84, 95% CI: 1;16-2;93) and temporomandibular joint sounds (adjusted OR: 1;64, 95% CI: 1;00-2;69). The findings show that in the general adult population there is a complex connection among bruxism, craniofacial pain and symptoms of masticatory disturbances. Furthermore, they suggest that the most direct relationship of bruxism may be with difficulties in mouth movements, but also an independent association may exist with craniofacial pain and other symptoms of temporomandibular disorder.

  6. Craniofacial Bone Grafting: Wolff's Law Revisited

    PubMed Central

    Oppenheimer, Adam J.; Tong, Lawrence; Buchman, Steven R.

    2008-01-01

    Bone grafts are used for the reconstruction of congenital and acquired deformities of the facial skeleton and, as such, comprise a vital component of the craniofacial surgeon's armamentarium. A thorough understanding of bone graft physiology and the factors that affect graft behavior is therefore essential in developing a more intelligent use of bone grafts in clinical practice. This article presents a review of the basic physiology of bone grafting along with a survey of pertinent concepts and current research. The factors responsible for bone graft survival are emphasized. PMID:22110789

  7. Craniofacial and Dental Features in Six Children With Cherubism.

    PubMed

    Stoor, Patricia; Suomalainen, Anni; Kemola, W; Arte, Sirpa

    2017-10-01

    Cherubism is an autosomal-dominant benign bone disorder, characterized by fibro-osseous lesions in the mandible and maxilla commonly caused by mutations in the SH3-binding protein 2-gene. The purpose of the authors' study was to analyze craniofacial and dental features of children diagnosed with cherubism, describe their treatment, and assess their dental age compared with norms for Finnish children. Six children were diagnosed, followed up and treated due to dental and skeletal disorders caused by cherubsim. The patients were followed up for an average of 91.5 months with emphasis on the skeletal changes and development of dentition. The treatment consisted of minor orthodontic treatment, dental extractions, and exposures. One patient underwent cosmetic mandibular surgery. All patients had lesions in the lower jaw and 5 of 6 patients had lesions in the maxilla as well. The patients were characterized by varying swelling of the jaws, premature loss of deciduous teeth in the affected area and widely spaced, displaced, un-erupted, or absent permanent teeth. The dental age was delayed at younger age but near to normal or even a little ahead at older age. Even though cherubism affects the jaws, jaw positions, and malocclusion, no common dentofacial proportions associated with the disease could be confirmed by cephalometric analysis. The surgical interventions did not provoke adverse reactions or local growth of the lesions.

  8. Pediatric craniofacial surgery: a review for the multidisciplinary team.

    PubMed

    Taub, Peter J; Lampert, Joshua A

    2011-11-01

    Pediatric craniofacial surgery is a specialty that grew dramatically in the 20th century and continues to evolve today. Out of the efforts to correct facial deformities encountered during World War II, the techniques of modern craniofacial surgery developed. An analysis of the relevant literature allowed the authors to explore this historical progression. Current advances in technology, tissue engineering, and molecular biology have further refined pediatric craniofacial surgery. The development of distraction osteogenesis and the progressive study of craniosynostosis provide remarkable examples of this momentum. The growing study of genetics, biotechnology, the influence of growth factors, and stem cell research provide additional avenues of innovation for the future. The following article is intended to reveal a greater understanding of pediatric craniofacial surgery by examining the past, present, and possible future direction. It is intended both for the surgeon, as well as for the nonsurgical individual specialists vital to the multidisciplinary craniofacial team.

  9. Positional Changes of the Ocular Organs During Craniofacial Development.

    PubMed

    Osaka, Miho; Ishikawa, Aoi; Yamada, Shigehito; Uwabe, Chigako; Imai, Hirohiko; Matsuda, Tetsuya; Yoneyama, Akio; Takeda, Tohoru; Takakuwa, Tetsuya

    2017-03-13

    The present study aimed to describe the positional changes of the ocular organs during craniofacial development; moreover, we examined the relationships among the ocular organs and other internal structures. To do this, we traced the positions of the ocular organs in 56 human early fetal samples at different stages of development using high-resolution magnetic resonance imaging and phase-contrast X-ray computed tomography. The eyes were located on the lateral side in the ventral view at Carnegie stage (CS) 16, and then changed their positions medially during development. The eyes remained in the neurocranium until CS17. However, the eyes changed their positions medially and caudally in the viscerocranium after CS18. The positional relationship between the eyes and pituitary gland changed in the lateral view as development progressed. Specifically, they were close to each other at CS17, but moved apart during the later stages of development. These positional changes were also demonstrated quantitatively with morphometric analyses. Based on the present data, the positional changes of the eyes can be categorized into phases, as follows: Phase 1, dramatic positional changes (early fetal period until CS23); and Phase 2, mild positional changes (stabilized; early fetal period after CS23). Notably, all absolute lengths measured in the present study linearly increased as the crown-rump length increased irrespective of the phase, while features of the measured angles and ratios differentially changed in Phases 1 and 2. The present data may help improve our understanding of both the normal and abnormal development of the ocular organs and craniofacial area. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Differences in Craniofacial Shape Among A/J and C57BL/6J Mice and Their F1 Crosses

    DTIC Science & Technology

    2006-05-31

    Many authors have found relationships between various craniofacial measurements and the occurrence of cleft lip (CL) in humans. Other authors have...found similar relationships in mice. Although it is widely recognized that a relationship exists between oral clefting and facial shape, this

  11. Craniofacial profile in Asian and white subjects with obstructive sleep apnoea

    PubMed Central

    Lam, B; Ip, M; Tench, E; Ryan, C

    2005-01-01

    Background: Clinical detection of structural narrowing of the upper airway may facilitate early recognition of obstructive sleep apnoea (OSA). To determine whether the craniofacial profile predicts the presence of OSA, the upper airway and craniofacial structure of 239 consecutive patients (164 Asian and 75 white subjects) referred to two sleep centres (Hong Kong and Vancouver) were prospectively examined for suspected sleep disordered breathing. Methods: All subjects underwent a history and physical examination with measurements of anthropometric parameters and craniofacial structure including neck circumference, thyromental distance, thyromental angle, and Mallampati oropharyngeal score. OSA was defined as an apnoea-hypopnoea index (AHI) of ⩾5/hour on full overnight polysomnography. Results: Discriminant function analysis indicated that the Mallampati score (F = 0.70), thyromental angle (F = 0.60), neck circumference (F = 0.54), body mass index (F = 0.53), and age (F = 0.53) were the best predictors of OSA. After controlling for ethnicity, body mass index and neck circumference, patients with OSA were older, had larger thyromental angles, and higher Mallampati scores than non-apnoeic subjects. These variables remained significantly different between OSA patients and controls across a range of cut-off values of AHI from 5 to 30/hour. Conclusions: A crowded posterior oropharynx and a steep thyromental plane predict OSA across two different ethnic groups and varying degrees of obesity. PMID:15923252

  12. MEPROCS framework for Craniofacial Superimposition: Validation study.

    PubMed

    Ibáñez, O; Vicente, R; Navega, D; Campomanes-Álvarez, C; Cattaneo, C; Jankauskas, R; Huete, M I; Navarro, F; Hardiman, R; Ruiz, E; Imaizumi, K; Cavalli, F; Veselovskaya, E; Humpire, D; Cardoso, J; Collini, F; Mazzarelli, D; Gibelli, D; Damas, S

    2016-11-01

    Craniofacial Superimposition (CFS) involves the process of overlaying a skull with a number of ante-mortem images of an individual and the analysis of their morphological correspondence. The lack of unified working protocols and the absence of commonly accepted standards, led to contradictory consensus regarding its reliability. One of the more important aims of 'New Methodologies and Protocols of Forensic Identification by Craniofacial Superimposition (MEPROCS)' project was to propose a common framework for CFS, what can be considered the first international standard in the field. The framework aimed to serve as a roadmap for avoiding particular assumptions that could bias the process. At the same time, it provides some empirical support to certain practices, technological means, and morphological criteria expected to facilitate the application of the CFS task and to improve its reliability. In order to confirm the utility and potential benefits of the framework use, there is a need to empirically evaluate it in CFS identification scenarios as close as possible to the reality. Thus, the purpose of this study is to validate the CFS framework developed. For that aim 12 participants were asked to report about a variable number of CFS following all the recommendations of the framework. The results are analysed and discussed according to the framework understanding and fulfilment, the participants' performance, and the correlation between expected decisions and those given by the participants. In view of the quantitative results and qualitative examination criteria we can conclude that those who follow the MEPROCS recommendations improve their performance.

  13. Computer-assisted innovations in craniofacial surgery.

    PubMed

    Rudman, Kelli; Hoekzema, Craig; Rhee, John

    2011-08-01

    Reconstructive surgery for complex craniofacial defects challenges even the most experienced surgeons. Preoperative reconstructive planning requires consideration of both functional and aesthetic properties of the mandible, orbit, and midface. Technological innovations allow for computer-assisted preoperative planning, computer-aided manufacturing of patient-specific implants (PSIs), and computer-assisted intraoperative navigation. Although many case reports discuss computer-assisted preoperative planning and creation of custom implants, a general overview of computer-assisted innovations is not readily available. This article reviews innovations in computer-assisted reconstructive surgery including anatomic considerations when using PSIs, technologies available for preoperative planning, work flow and process of obtaining a PSI, and implant materials available for PSIs. A case example follows illustrating the use of this technology in the reconstruction of an orbital-frontal-temporal defect with a PSI. Computer-assisted reconstruction of complex craniofacial defects provides the reconstructive surgeon with innovative options for challenging reconstructive cases. As technology advances, applications of computer-assisted reconstruction will continue to expand.

  14. Three-dimensional imaging in craniofacial surgery.

    PubMed

    Zonneveld, F W; Lobregt, S; van der Meulen, J C; Vaandrager, J M

    1989-01-01

    Over the past decade, three-dimensional (3-D) imaging has been developed to such a stage of perfection and to such a level of interactive selective imaging of specific anatomic and pathologic structures that craniofacial surgeons can now use this technique effectively in the planning of complicated reconstructive surgery. In addition, modeling techniques have been devised that can be used in surgical simulation and in the manufacture of implants and prosthetic devices. The technical aspects of 3-D imaging are discussed in relation to their applications in craniofacial surgery, and reference is made to the literature describing these techniques in full detail. The results are illustrated with cases that the authors have processed by means of: (a) a clinical research program that was developed on a general purpose computer which provided full flexibility in changing and improving the reconstruction algorithms (Lobregt algorithms and DEC VAX 750 computer), (b) a system under development (Pixar PICS 2000), and (c) a commercial system (Cemax 1500X). Finally, a number of emerging techniques are discussed such as surgical stimulation (electronic sculpting), and trends such as multimodality imaging.

  15. Craniofacial characteristics of children with mild hypodontia.

    PubMed

    Vucic, Strahinja; Dhamo, Brunilda; Kuijpers, Mette A R; Jaddoe, Vincent W V; Hofman, Albert; Wolvius, Eppo B; Ongkosuwito, Edwin M

    2016-10-01

    The aim of our study was to evaluate the craniofacial characteristics of children with mild hypodontia using conventional and principal component (PC) analysis. We used radiographic images of 124 children (8-12 years old) with up to 4 missing teeth (55 boys, 69 girls) and of 676 reference children (365 boys, 311 girls) from the Rotterdam Generation R Study and the Nijmegen Growth Study in The Netherlands. Fifteen cephalometric measurements of children with hypodontia were compared with those of the reference children. Moreover, cephalometric parameters were combined into standardized PC scores using PC analysis, and the components were compared between the 2 groups. PC analysis showed common dental characteristics for all types of hypodontia: a significant increase of the interincisal angle, and decreases of the maxillary and mandibular incisor angles. Other findings were consistent when both methods were applied: (1) anterior hypodontia was significantly associated with the high-angle (hyperdivergent) craniofacial pattern, (2) the tendency toward a Class III malocclusion was identified in maxillary hypodontia, and (3) we observed a significant reduction of lower posterior facial height in children with posterior and mandibular hypodontia. Our findings suggest that children with mild hypodontia have distinctive skeletal and dental features. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  16. Stature estimation from craniofacial anthropometry in Bangladeshi Garo adult females.

    PubMed

    Akhter, Z; Banu, L A; Alam, M M; Rahman, M F

    2012-07-01

    Estimation of stature is an important tool in forensic examination especially in unknown, highly decomposed, fragmentary and mutilated human remains. When the evidences are skeletal remains; forensic anthropology has put forward means to estimate the stature from the skeletal and even from fragmentary bones. Sometimes, craniofacial remains are brought in for forensic and postmortem examination. In such a situation, estimation of stature becomes equally important along with other parameters like age, sex, race, etc. Today, anthropometry plays an important role in industrial design, clothing design, ergonomics and architecture where statistical data about the distribution of body dimensions in the population are used to optimize products. It is well established that a single standard of craniofacial aesthetics is not appropriate for application to diverse racial and ethnic groups. Bangladesh is a country not only for the Bengalis; the country harbours many cultures and people of different races because of the colonial rules of the past regimes. Like other ethnic groups, the Garos (study subjects) have their own set of language, social structure, cultures and economic activities and religious values. In the above context, the present study was attempted to establish ethnic specific anthropometric data for the Bangladeshi Garo adult females. The study also attempted to find out the correlation of the craniofacial dimensions with stature and to determine multiplication factors. The study was an observational, cross-sectional and primarily descriptive in nature with some analytical components. The study was carried out with a total number of one hundred Garo adult females, aged between 25-45 years. Craniofacial dimension such as head circumference, head length, facial height from 'nasion' to 'gnathion', bizygomatic breadth and stature were measured using a measuring tape, spreading caliper, steel plate and steel tape and sliding caliper. The data were then statistically

  17. Epigenetic crosstalk: a molecular language in human metabolic disorders.

    PubMed

    Martinez-Jimenez, Celia P; Sandoval, Juan

    2015-06-01

    Technological breakthroughs are emphasizing the impact of epigenetic mechanisms in human health highlighting the importance of a fine-tune orchestration of DNA methylation, micro RNAs, histone modifications, and chromatin structure. Transcriptional regulators sense the concentration of intermediary metabolites associated to a wide variety of biological processes including the long-term imprinting and heritable DNA methylation. Recent epigenetic mechanisms associated with cholesterol and lipid homeostasis have a critical impact in the susceptibility, development and progression of complex diseases such as type 2 diabetes mellitus, non-alcoholic fatty liver, obesity and metabolic syndrome. The heritability of epigenetic states emerge as an additional level of complexity where the extension of somatic as well as inherited epigenetic modifications may require a thoughtful reconsideration in many human diseases related with metabolic disorders.

  18. Modeling human neurological disorders with induced pluripotent stem cells.

    PubMed

    Imaizumi, Yoichi; Okano, Hideyuki

    2014-05-01

    Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained

  19. Hypomorphic PCNA mutation underlies a human DNA repair disorder

    PubMed Central

    Baple, Emma L.; Chambers, Helen; Cross, Harold E.; Fawcett, Heather; Nakazawa, Yuka; Chioza, Barry A.; Harlalka, Gaurav V.; Mansour, Sahar; Sreekantan-Nair, Ajith; Patton, Michael A.; Muggenthaler, Martina; Rich, Phillip; Wagner, Karin; Coblentz, Roselyn; Stein, Constance K.; Last, James I.; Taylor, A. Malcolm R.; Jackson, Andrew P.; Ogi, Tomoo; Lehmann, Alan R.; Green, Catherine M.; Crosby, Andrew H.

    2014-01-01

    Numerous human disorders, including Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and trichothiodystrophy, result from the mutation of genes encoding molecules important for nucleotide excision repair. Here, we describe a syndrome in which the cardinal clinical features include short stature, hearing loss, premature aging, telangiectasia, neurodegeneration, and photosensitivity, resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding clamp protein essential for DNA replication and repair. Due to this fundamental role, mutations in PCNA that profoundly impair protein function would be incompatible with life. Interestingly, while the p.Ser228Ile alteration appeared to have no effect on protein levels or DNA replication, patient cells exhibited marked abnormalities in response to UV irradiation, displaying substantial reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change also profoundly altered PCNA’s interaction with Flap endonuclease 1 and DNA Ligase 1, DNA metabolism enzymes. Together, our findings detail a mutation of PCNA in humans associated with a neurodegenerative phenotype, displaying clinical and molecular features common to other DNA repair disorders, which we showed to be attributable to a hypomorphic amino acid alteration. PMID:24911150

  20. Genomic disorders: A window into human gene and genome evolution

    PubMed Central

    Carvalho, Claudia M. B.; Zhang, Feng; Lupski, James R.

    2010-01-01

    Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of the mechanism, LCRs can mediate or stimulate rearrangements, inciting genomic instability and generating dynamic and unstable regions prone to rapid molecular evolution. In humans, copy-number variation (CNV) has been implicated in common traits such as neuropathy, hypertension, color blindness, infertility, and behavioral traits including autism and schizophrenia, as well as disease susceptibility to HIV, lupus nephritis, and psoriasis among many other clinical phenotypes. The same mechanisms implicated in the origin of genomic disorders may also play a role in the emergence of segmental duplications and the evolution of new genes by means of genomic and gene duplication and triplication, exon shuffling, exon accretion, and fusion/fission events. PMID:20080665

  1. 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.

  2. [Research and clinical application of computer-aided design of craniofacial prosthesis using mirror technique].

    PubMed

    Zhan, Ming-Kun; Zhao, Jia-Qi; Mu, Xiong-Zheng; Qi, Zuo-Liang; Wei, Min

    2008-09-01

    To explore the feasibility of creating a 3D-CAD model of craniofacial prostheses through mirror technique to repair the unilateral craniofacial defects and restore craniofacial symmetry. Patients with unilateral craniofacial defects underwent spiral CT scanning. CAD3-D image was reconstructed ad 3-D CAD model of craniofacial prosthesis was created with mirror technique, Boolean operation and rapid prototyping technique. Then the prosthesis made of bioactive artificial bone was made through plaster cavity block. 15 cases were treated with no complications. Good symmetry was achieved after operation. Designing the craniofacial prosthesis with mirror technique guarantees excellent functional and cosmetic results for repairing the unilateral craniofacial defects.

  3. Psychosocial functioning in adults with congenital craniofacial conditions.

    PubMed

    Roberts, R M; Mathias, J L

    2012-05-01

    To examine the psychosocial functioning of adults with congenital craniofacial conditions relative to normative data. Single sample cross-sectional design. The Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide, which is one of the main craniofacial treatment centers in Australia. Adults (N  =  93) with congenital craniofacial conditions (excluding cleft lip/palate) who were treated in the Australian Craniofacial Unit. All participants completed self-report scales assessing health-related quality of life (SF-36); life satisfaction, anxiety, and depression (HADS); self-esteem (Rosenberg); appearance-related concerns; perceived social support; and social anxiety. Overall, participants were very similar in psychosocial function to the general population. However, adults with craniofacial conditions were less likely to be married and have children (females), were more likely to be receiving a disability pension, and reported more appearance-related concerns and less social support from friends. They also reported more limitations in both their social activities, due to physical or emotional problems, and usual role activities, because of emotional problems, as well as poorer mental health. These results give cause to be very positive about the long-term outcomes of children who are undergoing treatment for craniofacial conditions, while also identifying specific areas that interventions could target.

  4. Frequency of craniofacial pain in patients with ischemic heart disease

    PubMed Central

    Bakhshi, Mahin; Rezaei, Rezvan; Baharvand, Maryam

    2017-01-01

    Background Referred craniofacial pain of cardiac origin might be the only symptom of ischemic heart accidents. This study aimed to determine the frequency of craniofacial pain in patients with ischemic heart disease. Material and Methods This cross-sectional study was accomplished on 296 patients who met the criteria of having ischemic heart disease. Data regarding demographics, medical history and referred craniofacial pain were recorded in data forms. In addition, patients underwent oral examination to preclude any source of dental origin. Chi-square test, Student’s t-test and backward regression model were used to analyze the data by means of SPSS software version 21. P<0.05 was considered significant. Results A total of 296 patients were studied comprising of 211 men (71%) and 85 women (29%) with the mean age of 55.8. Craniofacial pain was experienced by 53 patients out of 296, 35 (66%) of whom were male and 18 (34%) were female. None of the patients experienced craniofacial pain solely. The most common sites of craniofacial pain were occipital and posterior neck (52.8%), head (43.3%), throat and anterior neck (41.5%) respectively. We found no relationship between craniofacial pain of cardiac origin with age, diabetes, hypertension, and family history. On the other hand, there was a significant relationship between hyperlipidemia and smoking with craniofacial pain of cardiac origin. Conclusions Radiating pain to face and head can be expected quite commonly during a cardiac ischemic event. Dental practitioners should be thoroughly aware of this symptomatology to prevent misdirected dental treatment and delay of medical care. Key words:Craniofacial pain, ischemic heart disease, myocardial infarction, angina pectoris, referred pain. PMID:28149470

  5. Similar impressions of humanness for human and artificial singing voices in autism spectrum disorders.

    PubMed

    Kuriki, Shinji; Tamura, Yuri; Igarashi, Miki; Kato, Nobumasa; Nakano, Tamami

    2016-08-01

    People with autism spectrum disorder (ASD) exhibit impairments in the perception of and orientation to social information related to humans, and some people with ASD show higher preference toward human-like robots than other humans. We speculated that this behavioural bias in people with ASD is caused by a weakness in their perception of humanness. To address this issue, we investigated whether people with ASD detect a subtle difference between the same song sung by human and artificial voices even when the lyrics, melody and rhythm are identical. People without ASD answered that the songs sung by a human voice evoked more impressions of humanness (human-likeness, animateness, naturalness, emotion) and more positive feelings (warmth, familiarity, comfort) than those sung by an artificial voice. In contrast, people with ASD had similar impressions of humanness and positive feelings for the songs sung by the human and artificial voices. The evaluations of musical characteristics (complexity, regularity, brightness) did not differ between people with and without ASD. These results suggest that people with ASD are weak in their ability to perceive psychological attributes of humanness.

  6. The ticking clock of Cayo Santiago macaques and its implications for understanding human circadian rhythm disorders.

    PubMed

    Zhdanova, Irina V; Rogers, Jeffrey; González-Martínez, Janis; Farrer, Lindsay A

    2016-01-01

    The circadian clock disorders in humans remain poorly understood. However, their impact on the development and progression of major human conditions, from cancer to insomnia, metabolic or mental illness becomes increasingly apparent. Addressing human circadian disorders in animal models is, in part, complicated by inverse temporal relationship between the core clock and specific physiological or behavioral processes in diurnal and nocturnal animals. Major advantages of a macaque model for translational circadian research, as a diurnal vertebrate phylogenetically close to humans, are further emphasized by the discovery of the first familial circadian disorder in non-human primates among the rhesus monkeys originating from Cayo Santiago. The remarkable similarity of their pathological phenotypes to human Delayed Sleep Phase Disorder (DSPD), high penetrance of the disorder within one branch of the colony and the large number of animals available provide outstanding opportunities for studying the mechanisms of circadian disorders, their impact on other pathological conditions, and for the development of novel and effective treatment strategies.

  7. The chick embryo as a model for the effects of prenatal exposure to alcohol on craniofacial development.

    PubMed

    Kiecker, Clemens

    2016-07-15

    Prenatal exposure to ethanol results in fetal alcohol spectrum disorder (FASD), a syndrome characterised by a broad range of clinical manifestations including craniofacial dysmorphologies and neurological defects. The characterisation of the mechanisms by which ethanol exerts its teratogenic effects is difficult due to the pleiotropic nature of its actions. Different experimental model systems have been employed to investigate the aetiology of FASD. Here, I will review studies using these different model organisms that have helped to elucidate how ethanol causes the craniofacial abnormalities characteristic of FASD. In these studies, ethanol was found to impair the prechordal plate-an important embryonic signalling centre-during gastrulation and to negatively affect the induction, migration and survival of the neural crest, a cell population that generates the cartilage and most of the bones of the skull. At the cellular level, ethanol appears to inhibit Sonic hedgehog signalling, alter levels of retionoic acid activity, trigger a Ca(2+)-CamKII-dependent pathway that antagonises WNT signalling, affect cytoskeletal dynamics and increase oxidative stress. Embryos of the domestic chick Gallus gallus domesticus have played a central role in developing a working model for the effects of ethanol on craniofacial development because they are easily accessible and because key steps in craniofacial development are particularly well established in the avian embryo. I will finish this review by highlighting some potential future avenues of fetal alcohol research. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pacific Craniofacial Team and Cleft Prevention Program.

    PubMed

    Tolarová, Marie M; Poulton, Donald; Aubert, Maryse M; Oh, HeeSoo; Ellerhorst, Thomas; Mosby, Terezie; Tolar, Miroslav; Boyd, Robert L

    2006-10-01

    There is no doubt modern genetics have greatly influenced our professional and personal lives during the last decade. Uncovering genetic causes of many medical and dental pathologies is helping to narrow the diagnosis and select a treatment plan that would provide the best outcome. Importantly, having an understanding of multifactorial etiology helps direct our attention toward prevention. We now understand much better our own health problems. In some cases, we can modify our lifestyle and diet in order to prevent "environmental factors" from triggering the mutated genes inherited from our parents. Good examples are diabetes and cardiovascular diseases. If we realize we might have inherited genes for cardiovascular problems from several ancestors who had heart attacks, we already know that these genes will make us only "susceptible" for disease. Those who exercise, watch one's weight, diet, and carefully monitor one's lifestyle will very likely--though possessing "susceptibility genes"--stay healthier and, maybe, will never experience any cardiovascular problems. In principle, the same applies for craniofacial anomalies, especially for nonsyndromic cleft lip and palate. One needs to understand genetic and environmental causes of nonsyndromic orofacial clefts in order to prevent them. With all this in mind, the Pacific Craniofacial Team and Cleft Prevention Program have been established at the Department of Orthodontics, University of the Pacific Arthur A. Dugoni School of Dentistry in San Francisco. A partnership with Rotaplast International, Inc., has made it possible for the faculty, orthodontic residents, and students to participate in 27 multidisciplinary cleft medical missions in underdeveloped and developing countries by donating professional and educational services, and, last but not least, by collecting valuable data and specimens to further research. A significant number of research studies, including 15 master of science theses, have been accomplished in

  9. Advanced airway management strategies for severe OSAS and craniofacial anomalies.

    PubMed

    Gungor, Anil

    Pediatric OSAS and craniofacial malformations present challenges that require innovative approaches and comprehensive treatment strategies. Synchronous airway lesions, craniofacial malformations, obstructive anomalies of the tongue base, nasal vault and choanae are commonly addressed by subspecialists from various clinical and surgical academic traditions who practice variable levels of required communication. This is not a mere social requirement but an important requisite for intelligent and effective airway management. Membership of dedicated airway, aero digestive or craniofacial teams are desirable but not required. I expect this clinical brief to help many brilliant clinicians in their pursuit of perfection. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Peripheral nerve stimulation for the treatment of neuropathic craniofacial pain.

    PubMed

    Slavin, K V

    2007-01-01

    Treatment of neuropathic pain in the region of head and face presents a challenging problem for pain specialists. In particular, those patients who do not respond to conventional treatment modalities usually continue to suffer from pain due to lack of reliable medical and surgical approaches. Peripheral nerve stimulation (PNS) has been used for treatment of neuropathic pain for many decades, but only recently it has been systematically applied to the craniofacial region. Here we summarize published experience with PNS in treatment of craniofacial pain and discuss some technical details of the craniofacial PNS procedure.

  11. Patterns of craniofacial integration in extant Homo, Pan, and Gorilla.

    PubMed

    Polanski, Joshua M; Franciscus, Robert G

    2006-09-01

    Brain size increased greatly during Pleistocene human evolution, while overall facial and dentognathic size decreased markedly. This mosaic pattern is due to either selective forces that acted uniquely on each functional unit in a modularized, developmentally uncoupled craniofacial complex, or alternatively, selection that acted primarily on one unit, with the other responding passively as part of a coevolved set of ontogenetically and evolutionarily integrated structures. Using conditional independence modeling on homologous linear measurements of the height, breadth, and depth of the cranium in Pan (n = 95), Gorilla (n = 102), and recent Homo (n = 120), we reject the null hypothesis of equal levels of overall cranial integration. While all three groups share the pattern of greater neurocranial integration with distinct separation between the face and neurocranium (modularization), family differences do exist. The apes are more integrated in their entire crania, but display a particularly strong pattern of integration within the facial complex related to prognathism. Modern humans display virtually no facial integration, a pattern which is likely related to their markedly decreased facial projection. Modern humans also differ from their great ape counterparts in being more integrated within the breadth dimension of the cranial vault, likely tied to the increase in brain size and eventual globularity seen in human evolution. That the modern human integration pattern differs from the ancestral African great ape pattern along the inverse neurocranial-facial trend seen in human evolution indicates that this shift in the pattern of integration is evolutionarily significant, and may help to clarify aspects of the current debate over defining modern humans. 2006 Wiley-Liss, Inc.

  12. Craniofacial Manifestations in Severe Nemaline Myopathy.

    PubMed

    Xue, Yunfeng; Magoulas, Pilar L; Wirthlin, John O; Buchanan, Edward P

    2017-05-01

    Nemaline myopathy (NM) is a rare congenital muscular disease characterized by the presence of rod (nemaline) bodies visualized on muscle biopsy. The disease is genetically and clinically heterogeneous, and the age of onset can vary from neonate to adult. Patients typically present initially with diffuse muscle weakness and hypotonia. The disease also afflicts facial musculature and can cause anomalous facial growth and development. The authors report a patient of early onset NM with significant craniofacial abnormalities. The untreated facial growth is discussed and illustrated in this article. The authors reviewed the current knowledge in the literature regarding the molecular and genetic pathogenesis of NM. The roles of both surgical and supportive management are discussed in this particular patient.

  13. Electrospun fibers for dental and craniofacial applications.

    PubMed

    Li, Guo; Zhang, Tong; Li, Meng; Fu, Na; Fu, Yao; Ba, Kai; Deng, Shuwen; Jiang, Yan; Hu, Jing; Peng, Qiang; Lin, Yunfeng

    2014-05-01

    Electrospinning has been employed extensively in tissue engineering to generate nanofibrous scaffolds from either natural or synthetic biodegradable polymers. Three-dimensional electrospun scaffolds can create a multi-scale environment capable of facilitating cell adhesion, proliferation, and differentiation. One such multi-scale scaffold incorporates nanofibrous features to mimic the extracellular matrix along with a porous network for the regeneration of a variety of tissues. This review will discuss nanofibrous scaffolds and their tissue-engineering applications in bone, cartilage, periodontium, tooth, and incorporated drug delivery systems. Combination with other technologies, electrospun scaffolds can contribute to the field of craniofacial regeneration and advance technology for tissue-engineered replacements in many physiological systems in near future.

  14. Nanofibrous scaffolds for dental and craniofacial applications.

    PubMed

    Gupte, M J; Ma, P X

    2012-03-01

    Tissue-engineering solutions often harness biomimetic materials to support cells for functional tissue regeneration. Three-dimensional scaffolds can create a multi-scale environment capable of facilitating cell adhesion, proliferation, and differentiation. One such multi-scale scaffold incorporates nanofibrous features to mimic the extracellular matrix along with a porous network for the regeneration of a variety of tissues. This review will discuss nanofibrous scaffold synthesis/fabrication, biological effects of nanofibers, their tissue- engineering applications in bone, cartilage, enamel, dentin, and periodontium, patient-specific scaffolds, and incorporated growth factor delivery systems. Nanofibrous scaffolds cannot only further the field of craniofacial regeneration but also advance technology for tissue-engineered replacements in many physiological systems.

  15. Reforming craniofacial orthodontics via stem cells.

    PubMed

    Mohanty, Pritam; Prasad, N K K; Sahoo, Nivedita; Kumar, Gunjan; Mohanty, Debapreeti; Sah, Sushila

    2015-01-01

    Stem cells are the most interesting cells in cell biology. They have the potential to evolve as one of the most powerful technologies in the future. The future refers to an age where it will be used extensively in various fields of medical and dental sciences. Researchers have discovered a number of sources from which stem cells can be derived. Craniofacial problems are very common and occur at all ages. Stem cells can be used therapeutically in almost every field of health science. In fact, many procedures will be reformed after stem cells come into play. This article is an insight into the review of the current researches being carried out on stem cells and its use in the field of orthodontics, which is a specialized branch of dentistry. Although the future is uncertain, there is a great possibility that stem cells will be used extensively in almost all major procedures of orthodontics.

  16. Craniofacial Secular Change in Recent Mexican Migrants.

    PubMed

    Spradley, Katherine; Stull, Kyra E; Hefner, Joseph T

    2016-01-01

    Research by economists suggests that recent Mexican migrants are better educated and have higher socioeconomic status (SES) than previous migrants. Because factors associated with higher SES and improved education can lead to positive secular changes in overall body form, secular changes in the craniofacial complex were analyzed within a recent migrant group from Mexico. The Mexican group represents individuals in the act of migration, not yet influenced by the American environment, and thus can serve as a starting point for future studies of secular change in this population group. The excavation of a historic Hispanic cemetery in Tucson, Arizona, also allows for a comparison between historic Hispanics and recent migrants to explore craniofacial trends over a broad time period, as both groups originate from Mexico. The present research addresses two main questions: (1) Are cranial secular changes evident in recent Mexican migrants? (2) Are historic Hispanics and recent Mexican migrants similar? By studying secular changes within a migrant population group, secular trends may be detected, which will be important for understanding the biological variation of the migrants themselves and will serve as a preliminary investigation of secular change within Mexican migrants. The comparison of a sample of recent Mexican migrants with a historic Hispanic sample, predominantly of Mexican origin, allows us to explore morphological similarities and differences between early and recent Mexicans within the United States. Vault and face size and a total of 82 craniofacial interlandmark distances were used to explore secular changes within the recent Mexican migrants (females, n = 38; males, n = 178) and to explore the morphological similarities between historic Hispanics (females, n = 54; males, n = 58) and recent migrants. Sexes were separated, and multivariate adaptive regression splines and basis splines (quadratic with one knot) were used to assess the direction and magnitude

  17. Studies of craniofacial development in rotating bioreactors.

    PubMed

    Duke, P J; Williams, P; Horn, N; Iverson, J; Leonhart, V; Kong, J; Montufar-Solis, D

    2007-07-01

    Several studies in our laboratory assessed the effect of 3-D culture in various rotating bioreactors on craniofacial development. Initially, mouse first branchial arches were cultured. Molar and incisor development occurred in both upper and lower jaws, but maxilla development was deficient because no brain was present. In a second study using excised whole heads, the oral epithelia fused and teeth did not develop. External structure of the face was obliterated, although internally, eye development was excellent. To preserve both internal spaces and external face structure, subsequent experiments used heads encapsulated in alginate. Teeth developed in these heads, though some interior components were necrotic. Additional experiments used older embryos, with already initiated structures, and less concentrated alginate. Orientation and unreserved identification of structures remain unresolved issues. Future studies will identify structures of interest using transcription factors unique to these structures at particular stages of fetal development.

  18. Reforming craniofacial orthodontics via stem cells

    PubMed Central

    Mohanty, Pritam; Prasad, N.K.K.; Sahoo, Nivedita; Kumar, Gunjan; Mohanty, Debapreeti; Sah, Sushila

    2015-01-01

    Stem cells are the most interesting cells in cell biology. They have the potential to evolve as one of the most powerful technologies in the future. The future refers to an age where it will be used extensively in various fields of medical and dental sciences. Researchers have discovered a number of sources from which stem cells can be derived. Craniofacial problems are very common and occur at all ages. Stem cells can be used therapeutically in almost every field of health science. In fact, many procedures will be reformed after stem cells come into play. This article is an insight into the review of the current researches being carried out on stem cells and its use in the field of orthodontics, which is a specialized branch of dentistry. Although the future is uncertain, there is a great possibility that stem cells will be used extensively in almost all major procedures of orthodontics. PMID:25767761

  19. [Management of craniofacial type 1 neurofibromatosis].

    PubMed

    Bachelet, J T; Combemale, P; Devic, C; Foray, N; Jouanneau, E; Breton, P

    2015-09-01

    Type I neurofibromatosis (NF) is the most common autosomal dominant disease. It concerns one in 3000 births, the penetrance is close to 100% and 50% of new cases are de novo mutations (17q11.2 chromosome 17 location). Cranio-maxillofacial region is concerned in 10% of the cases, in different forms: molluscum neurofibroma, plexiform neurofibroma, cranio-orbital neurofibroma, parotido-jugal neurofibroma, cervical neurofibroma. These lesions have different prognosis depending on the craniofacial localization: ocular functional risk, upper airway compressive risk, nerve compression risk, aesthetic and social impact. The maxillofacial surgeon in charge of patients with type I NF should follow the patient from the diagnosis and organize the different surgical times in order to take care about the different issues: vital, functional and aesthetic. We describe the treatment of facial localizations of type 1 NF as it is done at the University Hospital of Lyon and at the Rhône-Alpes-Auvergne neurofibromatosis reference center.

  20. Is somnambulism a distinct disorder of humans and not seen in non-human primates?

    PubMed

    Kantha, S S

    2003-01-01

    Though somnambulism (sleepwalking) is a well-recognized sleep disorder in humans, a biomedical literature search in Medline and Primate Literature bibliographic databases showed no publications on sleepwalking in non-human primates. From this finding, two inferences can be made. First is that somnambulism may be present in non-human primates; but due to limitations in expertise and methodological resources as well as narrow focus of research interest, until now researchers have not detected it in wild and/or captive conditions. Second, somnambulism does not exist in non-human primates including apes (chimpanzee, gorilla, orang-utan and gibbon); and thus, it is a unique behavioral disorder present only in humans. It is premature to conclude which of these two inferences is correct. In Jane Goodall's view, sleepwalking behavior is absent in chimpanzees. If further field observations can confirm Goodall's assertion that somnambulism is indeed absent in chimpanzees, it will be of evolutionary and medical interest to know why this parasomnic behavior became established in humans during the past 5.5 million years or so.

  1. Prevention of craniofacial injuries in football.

    PubMed

    Ranalli, D N

    1991-10-01

    The evolution of rules and regulations governing the development and use of protective football equipment for the prevention of craniofacial and intraoral traumatic injuries to football players have reduced substantially the occurrence of these injuries. Protective football equipment such as helmets, facemasks, and intraoral mouthguards have undergone numerous developmental changes to improve their effectiveness in preventing traumatic injuries to the head, face, and mouth of participants in football during practice sessions as well as in game situations. Unfortunately, however, some of these types of injuries do continue to occur. Various regulatory agencies and football governing bodies have established quality performance standards for equipment and have enacted rulings for their proper use. Penalties have been assessed for rule infractions to aid in curtailing the misuse of such equipment, as occurs for example, when the helmet is used to spear tackle an opponent or when the facemask is grasped, pulled, or twisted by an opposing player. Dentists can contribute significantly to the overall well-being of their patients who participate in football by providing information and advice regarding the proper use of protective football equipment to prevent craniofacial and intraoral traumatic football-related injuries, by fabricating properly fitted mouthguards as one aspect of their total practice of dentistry, and by providing high-quality and expeditious emergency and long-term treatment subsequent to football-related intraoral traumatic injuries. In addition, dentists can contribute on a larger scale to the overall well-being of football athletes by participating in community service activities such as mouthguard days, as consultants to football teams, as team dentists, or as advisors to those interested in research and development to improve protective football equipment, and to those responsible for sponsoring more stringent regulations for player safety in

  2. Craniofacial profile in Southern Chinese with hypodontia.

    PubMed

    Chan, Doreen W S; Samman, Nabil; McMillan, Anne S

    2009-06-01

    The association between craniofacial morphology and congenitally missing teeth is at present unclear. The aims of this study were to investigate whether hypodontia is associated with changes in the sagittal skeletal profile and to identify putative relationships between the skeletal profile and the severity of hypodontia. In a cross-sectional analytical study, the craniofacial structure and profile based on two-dimensional lateral cephalograms of Southern Chinese hypodontia patients (n = 49, 24 males, 25 females, mean age 16.4 years) and a comparison group without hypodontia (n = 41, 15 males, 26 females, mean age 16.7 years) were compared. The hypodontia patients were divided into three subgroups according to the severity of hypodontia (mild: < or =5, moderate: 6-9, and severe: > or =10 congenitally missing permanent teeth). All hypodontia patients had a significantly reduced mandibular plane, ANB, and face height compared with the control group (P < 0.05). A significant increase in chin thickness was also observed in the hypodontia patients (P < 0.05). As the severity of hypodontia increased from moderate to severe, a tendency to develop a retrognathic maxilla and a Class III skeletal relationship was noted in addition to the above features, making the already thick chin even more prominent. Statistically significant correlations (Pearson's correlation coefficient) were found between the number of missing teeth and SNA, NAFH, and ANB angles, the mandibular plane, chin thickness, and face height. In Southern Chinese subjects, hypodontia was associated with a shorter face, a flatter mandibular plane, a more pronounced chin, and a Class III skeletal profile. In severe hypodontia subjects, the maxilla was more retrognathic with a greater predilection to a Class III skeletal relationship.

  3. Survey of the human acetylator polymorphism in spontaneous disorders.

    PubMed Central

    Evans, D A

    1984-01-01

    There is ample evidence that the human acetylator phenotypes are associated with drug induced phenomena. It is principally the slow acetylators who exhibit toxic adverse effects because of their relative inability to detoxify the original drug compounds. In rare instances, however, it is the rapid acetylators who are at a disadvantage. In the matter of association of spontaneous disease with either acetylator phenotype, there are two groups of disorders to consider. First, disorders in which carcinogenic amines are known to be an aetiological factor. This is because these amines are substrates for the polymorphic N-acetyltransferase activity and hence there is a possible rational basis for searching for an association. Secondly, other disorders where searches for associations are based more on hunches. In the first group there is a definite statistical association between cancer of the bladder and the slow acetylator phenotype. In prevalence studies the slow phenotype is 39% more associated with bladder cancer than is the rapid phenotype. On the basis of the evidence now available it is not possible to say whether this association is because slow acetylators develop the disease more frequently or whether they survive longer. In the second group the relevant studies show (1) a greatly increased prevalence of slow acetylators in Gilbert's disease; (2) a confirmed association between the rapid acetylator phenotype and diabetes; (3) a possible association between the rapid acetylator phenotype and breast cancer; (4) a possible association between the slow acetylator phenotype and leprosy in Chinese patients; (5) an earlier age of onset of thyrotoxicosis (Graves' disease) in slow acetylators than in rapid acetylators; (6) no evidence of an association between either phenotype and spontaneous systemic lupus erythematosus. PMID:6387123

  4. 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

  5. A phenotype-driven ENU mutagenesis screen identifies novel alleles with functional roles in early mouse craniofacial development.

    PubMed

    Sandell, Lisa L; Iulianella, Angelo; Melton, Kristin R; Lynn, Megan; Walker, Macie; Inman, Kimberly E; Bhatt, Shachi; Leroux-Berger, Margot; Crawford, Michelle; Jones, Natalie C; Dennis, Jennifer F; Trainor, Paul A

    2011-04-01

    Proper craniofacial development begins during gastrulation and requires the coordinated integration of each germ layer tissue (ectoderm, mesoderm, and endoderm) and its derivatives in concert with the precise regulation of cell proliferation, migration, and differentiation. Neural crest cells, which are derived from ectoderm, are a migratory progenitor cell population that generates most of the cartilage, bone, and connective tissue of the head and face. Neural crest cell development is regulated by a combination of intrinsic cell autonomous signals acquired during their formation, balanced with extrinsic signals from tissues with which the neural crest cells interact during their migration and differentiation. Although craniofacial anomalies are typically attributed to defects in neural crest cell development, the cause may be intrinsic or extrinsic. Therefore, we performed a phenotype-driven ENU mutagenesis screen in mice with the aim of identifying novel alleles in an unbiased manner, that are critically required for early craniofacial development. Here we describe 10 new mutant lines, which exhibit phenotypes affecting frontonasal and pharyngeal arch patterning, neural and vascular development as well as sensory organ morphogenesis. Interestingly, our data imply that neural crest cells and endothelial cells may employ similar developmental programs and be interdependent during early embryogenesis, which collectively is critical for normal craniofacial morphogenesis. Furthermore our novel mutants that model human conditions such as exencephaly, craniorachischisis, DiGeorge, and Velocardiofacial sydnromes could be very useful in furthering our understanding of the complexities of specific human diseases. Copyright © 2011 Wiley-Liss, Inc.

  6. A Phenotype-Driven ENU Mutagenesis Screen Identifies Novel Alleles With Functional Roles in Early Mouse Craniofacial Development

    PubMed Central

    Sandell, Lisa L.; Iulianella, Angelo; Melton, Kristin R.; Lynn, Megan; Walker, Macie; Inman, Kimberly E.; Bhatt, Shachi; Leroux-Berger, Margot; Crawford, Michelle; Jones, Natalie C.; Dennis, Jennifer F.; Trainor, Paul A.

    2012-01-01

    Summary Proper craniofacial development begins during gastrulation and requires the coordinated integration of each germ layer tissue (ectoderm, mesoderm, and endoderm) and its derivatives in concert with the precise regulation of cell proliferation, migration, and differentiation. Neural crest cells, which are derived from ectoderm, are a migratory progenitor cell population that generates most of the cartilage, bone, and connective tissue of the head and face. Neural crest cell development is regulated by a combination of intrinsic cell autonomous signals acquired during their formation, balanced with extrinsic signals from tissues with which the neural crest cells interact during their migration and differentiation. Although craniofacial anomalies are typically attributed to defects in neural crest cell development, the cause may be intrinsic or extrinsic. Therefore, we performed a phenotype-driven ENU mutagenesis screen in mice with the aim of identifying novel alleles in an unbiased manner, that are critically required for early craniofacial development. Here we describe 10 new mutant lines, which exhibit phenotypes affecting frontonasal and pharyngeal arch patterning, neural and vascular development as well as sensory organ morphogenesis. Interestingly, our data imply that neural crest cells and endothelial cells may employ similar developmental programs and be interdependent during early embryogenesis, which collectively is critical for normal craniofacial morphogenesis. Furthermore our novel mutants that model human conditions such as exencephaly, craniorachischisis, DiGeorge, and Velocardiofacial sydnromes could be very useful in furthering our understanding of the complexities of specific human diseases. PMID:21305688

  7. Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

    PubMed Central

    2014-01-01

    Glycosaminoglycans (GAGs) are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs. PMID:25126564

  8. In vivo impact of Dlx3 conditional inactivation in Neural Crest-Derived Craniofacial Bones

    PubMed Central

    Duverger, Olivier; Isaac, Juliane; Zah, Angela; Hwang, Joonsung; Berdal, Ariane; Lian, Jane B.; Morasso, Maria I.

    2012-01-01

    Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. PMID:22886599

  9. 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.

  10. Quality difference in craniofacial pain of cardiac vs. dental origin.

    PubMed

    Kreiner, M; Falace, D; Michelis, V; Okeson, J P; Isberg, A

    2010-09-01

    Craniofacial pain, whether odontogenic or caused by cardiac ischemia, is commonly referred to the same locations, posing a diagnostic challenge. We hypothesized that the validity of pain characteristics would be high in assessment of differential diagnosis. Pain quality, intensity, and gender characteristics were assessed for referred craniofacial pain from dental (n = 359) vs. cardiac (n = 115) origin. The pain descriptors "pressure" and "burning" were statistically associated with pain from cardiac origin, while "throbbing" and "aching" indicated an odontogenic cause. No gender differences were found. These data should now be added to those craniofacial pain characteristics already known to point to acute cardiac disease rather than dental pathology, i.e., pain provocation/aggravation by physical activity, pain relief at rest, and bilateralism. To initiate prompt and appropriate treatment, dental and medical clinicians as well as the public should be alert to those clinical characteristics of craniofacial pain of cardiac origin.

  11. [Personal identification using information from cranio-facial region].

    PubMed

    Minaguchi, Kiyoshi

    2007-11-01

    Much of Forensic Odontology is concerned with personal identification, through examination of cranio-facial region. This paper describes several studies in which we worked with materials derived from cranio-facial region. The following topics are addressed : (1) Human saliva contains proteins specific to salivary glands, proteins which are highly polymorphic compared with those found in other body fluids. In particular, six genes for proline-rich proteins coded many proteins found in human saliva, and we found several of them. At least five kinds of cystatin are secreted in saliva. We constructed recombinant polymorphic proteins, cystatin SAl and SA2. Using these proteins, we compared effects of amino acid mutation on protease inhibitor activity, and demonstrated a novel function for type-2 cystatin cytokine-inducing activity. (2) Among autosomal STR loci, we identified the D12S67 locus as highly polymorphic, with a heterozygosity of 95%, by investigating differences in nucleotide repeat units. Highly polymorphic autosomal STR loci offer an effective forensic tool under certain conditions, in addition to multiplex PCR, and therefore merit further study in forensic practice. (3) Although digitalization is prevalent in photography, analog images are preferable in certain circumstances as they offer better resolution. (4) Usually, information on mtDNA polymorphisms from HV1 and HV2 in the control region is used in forensic practice. However, information from the coding region considerably increases the discrimination power of mtDNA polymorphisms. It is important to increase the volume of coding region information available with regard to mtDNA polymorphisms for future forensic practice. (5) Y-STR polymorphisms are closely associated with binary haplogroups, and it is possible to estimate a binary haplogroup from an STR haplotype. (6) Mitochondrial DNA and Y-chromosomal polymorphisms can be used to determine geographic origin in individuals from East Asia, something

  12. The Aponeurotic Tension Model of Craniofacial Growth in Man

    PubMed Central

    Standerwick, Richard G; Roberts, W. Eugene

    2009-01-01

    Craniofacial growth is a scientific crossroad for the fundamental mechanisms of musculoskeletal physiology. Better understanding of growth and development will provide new insights into repair, regeneration and adaptation to applied loads. Traditional craniofacial growth concepts are insufficient to explain the dynamics of airway/vocal tract development, cranial rotation, basicranial flexion and the role of the cranial base in expression of facial proportions. A testable hypothesis is needed to explore the physiological pressure propelling midface growth and the role of neural factors in expression of musculoskeletal adaptation after the cessation of anterior cranial base growth. A novel model for craniofacial growth is proposed for: 1. brain growth and craniofacial adaptation up to the age of 20; 2. explaining growth force vectors; 3. defining the role of muscle plasticity as a conduit for craniofacial growth forces; and 4. describing the effect of cranial rotation in the expression of facial form. Growth of the viscerocranium is believed to be influenced by the superficial musculoaponeurotic systems (SMAS) of the head through residual tension in the occipitofrontalis muscle as a result of cephalad brain growth and cranial rotation. The coordinated effects of the regional SMAS develop a craniofacial musculoaponeurotic system (CFMAS), which is believed to affect maxillary and mandibular development. PMID:19572022

  13. Craniofacial Dermoid Cysts: Histological Analysis and Inter-site Comparison

    PubMed Central

    Reissis, Dimitris; Pfaff, Miles J.; Patel, Anup; Steinbacher, Derek M.

    2014-01-01

    Introduction: Dermoid cysts are common, benign, embryologically derived soft tissue cysts that can arise at a variety of craniofacial sites. It is not known whether specific histological variations exist between the different craniofacial sites. This study aims to establish whether inter-site histologic differences exist between periorbital, nasal, scalp, and postauricular dermoid cysts and analyze these in context of their distinct embryological origin and varied clinical presentation. Methods: A retrospective review of craniofacial dermoid cysts was performed. Using light microscopy with hematoxylin and eosin staining, histological appearance was directly compared between craniofacial sites. Results: All (n = 16) cysts contained keratinizing, stratified squamous epithelial lining, intraluminal keratin, and hair. Sebaceous glands were commonly present (n = 13). Eccrine (sweat) glands were less common (n = 3). Structures of mesodermal origin were seen in three periorbital cysts. Only the six ruptured cysts showed evidence of inflammation. Conclusions: Histological properties of dermoid cysts are conserved between craniofacial sites (periorbital, nasal, scalp, and postauricular). This reflects the consistency of ectodermal inclusion during early embryological development, which is independent of specific craniofacial site or surrounding anatomical structures. PMID:25191150

  14. Antimicrobial surfaces for craniofacial implants: state of the art

    PubMed Central

    Actis, Lisa; Gaviria, Laura; Guda, Teja

    2013-01-01

    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. PMID:24471018

  15. 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.

  16. The aponeurotic tension model of craniofacial growth in man.

    PubMed

    Standerwick, Richard G; Roberts, W Eugene

    2009-05-22

    Craniofacial growth is a scientific crossroad for the fundamental mechanisms of musculoskeletal physiology. Better understanding of growth and development will provide new insights into repair, regeneration and adaptation to applied loads. Traditional craniofacial growth concepts are insufficient to explain the dynamics of airway/vocal tract development, cranial rotation, basicranial flexion and the role of the cranial base in expression of facial proportions. A testable hypothesis is needed to explore the physiological pressure propelling midface growth and the role of neural factors in expression of musculoskeletal adaptation after the cessation of anterior cranial base growth. A novel model for craniofacial growth is proposed for: 1. brain growth and craniofacial adaptation up to the age of 20; 2. explaining growth force vectors; 3. defining the role of muscle plasticity as a conduit for craniofacial growth forces; and 4. describing the effect of cranial rotation in the expression of facial form.Growth of the viscerocranium is believed to be influenced by the superficial musculoaponeurotic systems (SMAS) of the head through residual tension in the occipitofrontalis muscle as a result of cephalad brain growth and cranial rotation. The coordinated effects of the regional SMAS develop a craniofacial musculoaponeurotic system (CFMAS), which is believed to affect maxillary and mandibular development.

  17. Craniofacial Features Resembling Frontonasal Dysplasia with a Tubulonodular Interhemispheric Lipoma in the Adult 3H1 tuft Mouse

    PubMed Central

    Fong, Keith S. K.; Cooper, Tiffiny Baring; Drumhiller, Wallace C.; Somponpun, Jack; Yang, Shiming; Ernst, Thomas; Chang, Linda; Lozanoff, Scott

    2012-01-01

    Intracranial lipomas are rare, but 45% of them occur along the midline cisterns between the hemispheres and are often associated with corpus callosum hypoplasia and craniofacial defects. They are difficult to detect, as they are generally asymptomatic and visible by MRI or by postmortem examination. The exact cause of these interhemispheric lipomas is not known, but they arise from a developmental defect resulting in the maldifferentiation of mesenchymal cells into mesodermal derivatives that are not normally present. We have identified a new mouse mutant called tuft, exhibiting a forebrain, intracranial lipoma with midline craniofacial defects resembling frontonasal dysplasia (FND) that arose spontaneously in our wild-type 3H1 colony. The tuft trait appears to be transmitted in recessive fashion, but approximately 80% less frequent than the expected Mendelian 25%, due to either incomplete penetrance or prenatal lethality. MRI and histological analysis revealed that the intracranial lipoma occurred between the hemispheres and often protruded through the sagittal suture. We also observed a lesion at the lamina terminalis that may indicate improper closure of the anterior neuropore. We have mapped the tuft trait to within an 18 cM region on mouse chromosome 10 by microsatellite linkage analysis and identified several candidate genes involved with craniofacial development and cellular differentiation of adipose tissue. tuft is the only known mouse model for midline craniofacial defects with an intracranial lipoma. Identifying the gene(s) and mutation(s) causing this early developmental defect will help us understand the pathogenesis of FND and related craniofacial disorders. PMID:22246904

  18. Interrogating the mouse thalamus to correct human neurodevelopmental disorders

    PubMed Central

    Schmitt, L. Ian; Halassa, Michael M.

    2016-01-01

    While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how basic circuit functions relate to thought and behavior. Neurodevelopmental disorders offer a window to addressing the first challenge given their strong genetic underpinnings, which can be linked to biological mechanisms. Such links have benefited from genetic modeling in the mouse, and in this review we highlight how this small mammal is now allowing us to crack neural circuits as well. We review recent studies of mouse thalamus, discussing how they revealed general principles that may underlie human perception and attention. Controlling the magnitude (gain) of thalamic sensory responses is a mechanism of attention, and the mouse has enabled its functional dissection at an unprecedented resolution. Further, modeling human genetic neurodevelopmental disease in the mouse has shown how diminished thalamic gain control can lead to attention deficits. This breaks new ground in how we untangle the complexity of psychiatric diseases; by making thalamic circuits accessible to mechanistic dissection, the mouse has not only taught us how they fundamentally work, but also how their dysfunction can be precisely mapped onto behavioral and cognitive deficits. Future studies promise even more progress, with the hope that principled targeting of identified thalamic circuits can be uniquely therapeutic. PMID:27725660

  19. Craniofacial osteoblast responses to polycaprolactone produced using a novel boron polymerisation technique and potassium fluoride post-treatment.

    PubMed

    Gough, J E; Christian, P; Scotchford, C A; Jones, I A

    2003-12-01

    There is no ideal material for craniofacial bone repair at present. The aim of this study was to test the biocompatibility of polycaprolactone (PCL) synthesised by a novel method allowing control of molecular weight and degradation rate, with regard to it being used as matrix for a biodegradable composite for craniofacial bone repair. Human primary craniofacial cells were used, isolated from paediatric skull after surgery. Cell responses were analysed using various assays and antibody staining. Cells attached and spread on the PCL in a similar manner to the Thermanox controls as shown by phalloidin staining of F-actin. Cells maintained the osteoblast phenotype as demonstrated by alkaline phosphatase assay and antibody staining throughout the time points studied, up to 28 days. Cells proliferated on the PCL as shown by a DNA assay. Collagen-1 staining showed extensive production of a collagen-1 containing extracellular matrix, which was also shown to be mineralised by alizarin red staining. Short-term (up to 48 h) attachment studies and long-term (up to 28 days) expression of markers of the osteoblast phenotype have been demonstrated on the PCL. This new method of synthesising PCL shows biocompatibility characteristics that give it potential to be used for craniofacial bone repair.

  20. 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

  1. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    PubMed

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  2. The role of serotonin and neurotransmitters during craniofacial development.

    PubMed

    Moiseiwitsch, J R

    2000-01-01

    Several neurotransmitters, in particular serotonin (5-HT), have demonstrated multiple functions during early development and mid-gestational craniofacial morphogenesis. Early studies indicated that 5-HT is present in the oocyte, where it appears to function as a regulator of cell cleavage. Later, it has a significant role during gastrulation, during which there are significant areas of 5-HT uptake in the primitive streak. Subsequently, in association with neurulation, 5-HT uptake is seen in the floor plate of the developing neural tube. During neural crest formation and branchial arch formation, 5-HT has been demonstrated to facilitate cell migration and stimulate cell differentiation. During morphogenesis of the craniofacial structures, 5-HT stimulates dental development and may aid in cusp formation. All of the most commonly prescribed antidepressant drugs inhibit serotonin uptake, yet they do not appear to cause major craniofacial malformations in vivo. Given the wide spectrum of effects that 5-HT has during development, it is difficult to understand why these anti-depressants are not major teratogens. Redundancy within the system may allow receptor and uptake pathways to function normally even with lower than normal levels of circulating serotonin. Serotonin-binding proteins, that are expressed in most craniofacial regions at critical times during craniofacial development, may have a buffering capacity that maintains adequate 5-HT tissue concentrations over a wide range of 5-HT serum concentrations. Dental development appears to be particularly sensitive to even small fluctuations in concentrations of 5-HT. Therefore, it may be that children of patients who have received selective serotonergic re-uptake inhibitors (such as Prozac and Zoloft) or the less selective tricyclic anti-depressant drugs (such as Elavil) would be at a higher risk for developmental dental defects such as anodontia and hypodontia. In this review, the evidence supporting a role for 5-HT

  3. Craniofacial morphology in patients with velocardiofacial syndrome.

    PubMed

    Dalben, Gisele da Silva; Richieri-Costa, Antonio; Taveira, Luís Antônio de Assis

    2010-05-01

    To compare cephalometric measurements of patients with and without velocardiofacial syndrome. Cross-sectional. Public tertiary craniofacial center. Lateral cephalograms of 18 patients with velocardiofacial syndrome and 18 controls without morphofunctional alterations, matched for gender and age; all cephalograms were obtained before orthodontic intervention. The cephalograms were manually traced and digitized for the achievement of linear and angular measurements. Individuals with velocardiofacial syndrome presented a reduced length of the skull base, retrusion of nasal bones, reduced posterior height of the maxilla, increased gonial angle, increased interincisal angle, greater lingual inclination of the mandibular incisors, reduced nasolabial angle, and reduced nasal depth compared with the control group. Patients with velocardiofacial syndrome presented morphological differences compared with individuals without morphofunctional alterations, which might be considered in the evaluation of patients with suspected diagnosis of the syndrome, as well as for the establishment of treatment protocols adequate to their needs. The present findings did not support the hypothesis of differences in pharyngeal dimensions mentioned by other authors, suggesting that the velopharyngeal insufficiency in these patients may be caused by functional alterations rather than by anatomical differences.

  4. Morphometrics, 3D Imaging, and Craniofacial Development

    PubMed Central

    Hallgrimsson, Benedikt; Percival, Christopher J.; Green, Rebecca; Young, Nathan M.; Mio, Washington; Marcucio, Ralph

    2017-01-01

    Recent studies have shown how volumetric imaging and morphometrics can add significantly to our understanding of morphogenesis, the developmental basis for variation and the etiology of structural birth defects. On the other hand, the complex questions and diverse imaging data in developmental biology present morphometrics with more complex challenges than applications in virtually any other field. Meeting these challenges is necessary in order to understand the mechanistic basis for variation in complex morphologies. This chapter reviews the methods and theory that enable the application of modern landmark-based morphometrics to developmental biology and craniofacial development, in particular. We discuss the theoretical foundations of morphometrics as applied to development and review the basic approaches to the quantification of morphology. Focusing on geometric morphometrics, we discuss the principal statistical methods for quantifying and comparing morphological variation and covariation structure within and among groups. Finally, we discuss the future directions for morphometrics in developmental biology that will be required for approaches that enable quantitative integration across the genotype-phenotype map. PMID:26589938

  5. Computerized craniofacial reconstruction: Conceptual framework and review.

    PubMed

    Claes, Peter; Vandermeulen, Dirk; De Greef, Sven; Willems, Guy; Clement, John Gerald; Suetens, Paul

    2010-09-10

    When confronted with a corpse that is unrecognizable due to its state of decomposition, soft-tissue mutilation or incineration, and if no other identification evidence is available, craniofacial reconstruction (CFR) can be a useful tool in the identification of the body. Traditional methods are based on manual reconstruction by physically modelling a face on a skull replica with clay or plasticine. The progress in computer science and the improvement of medical imaging technologies during recent years has had a significant impact on this domain. New, fast, flexible and computer-based objective reconstruction programs are under development. Employing the newer technologies and permanently evaluating the obtained results will hopefully lead to more accurate reconstructions, beneficial to the added value of CFR methods during crime-scene investigations. A general model-based workflow is observed, when analysing computerized CFR techniques today. The main purpose of this paper is to give an overview of existing computer-based CFR methods up to date defined within a common framework using a general taxonomy. The paper will also discuss the various alternatives and problems which arise during the process of designing a CFR program. Crown Copyright 2010. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Robot-assisted placement of craniofacial implants.

    PubMed

    Klein, Martin; Hein, Andreas; Lueth, Tim; Bier, Jürgen

    2003-01-01

    The purpose of this study was to improve and accelerate the rehabilitation process for patients with severe ear microtia with an implant-anchored auricular prosthesis. A medically approved robot system was used to place the craniofacial implants and a new process was developed for preoperative fabrication of the prosthesis using a rapid prototyping technique. Preoperatively, after computerized tomography, the implant positions were determined in a planning tool according to bone availability and esthetic considerations. Intraoperatively, the robot showed the surgeon the planned implant positions and guided the placement procedure. The accuracy measurements showed that with this robot system, absolute implant position accuracy of approximately -0.5 +/- 0.4 mm, a relative accuracy between the implants of approximately 0.2 +/- 0.5 mm, and a deviation from the parallel position of approximately 0.6 +/- 0.5 degrees were achieved. Thirty implants were placed in 13 patients with robot assistance with no intraoperative injuries. This technique made it possible to apply the preoperatively fabricated auricular prosthesis directly after surgery. From this experience it can be concluded that the robot system and the new manufacturing concept for anaplastology can be applied advantageously in other areas of the head as well.

  7. Craniofacial team management in Apert syndrome.

    PubMed

    Oberoi, Snehlata; Hoffman, William Y; Vargervik, Karin

    2012-04-01

    Apert syndrome is one of the rarest of the craniosynostosis syndromes. Affected persons have extensive structural and functional impairments, some of which can be life threatening. Management requires team care from infancy to adulthood. The purposes of this article are to assess the outcomes in individuals with Apert syndrome after completion of treatment and to review current protocols for craniofacial team care and dental, orthodontic, and orthognathic surgical management. This was a retrospective cohort study of 8 subjects with Apert syndrome. Cephalograms at 2 time points were compared: adolescence (before midface advancement) and at least 1 year after advancement. The cephalometric values were compared with paired t tests. Team protocols are delineated. Measurements indicating forward positioning of the maxilla increased significantly: SNA by 10.7° (P = 0.002) and midface length by 9.6 mm (P = 0.002). Sagittal jaw relationship improved significantly as well: ANB by 14° (P = 0.004) and the Wits appraisal by 8 mm (P = 0.003). Vertical dimensions also increased. All individuals had significantly improved and stable positions of the midface and normalized facial profiles after treatment. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  8. Endoscopic craniofacial resection. Indications and technical aspects.

    PubMed

    Llorente, José Luis; López, Fernando; Suárez, Vanessa; Costales, María; Moreno, Carla; Suárez, Carlos

    2012-01-01

    Anterior craniofacial resection (CFR) is a standardised procedure for the treatment of tumours involving the anterior skull base. We present our experience in the endoscopic treatment of these tumours. A retrospective analysis was performed of patients treated by endoscopic anterior CFR in our Department from 2004 until 2011. Thirty-two patients were analysed. Mean follow-up was 28 months (range: 6-84 months). The most frequent pathological entity was adenocarcinoma (60%), followed by undifferentiated carcinoma (13%). According to TNM classification, malignant epithelial tumour staging was T3 in 9%, T4a in 53% and T4b in 19% of the malignant epithelial tumours. The complication rate was 6% and the resection was complete in 91% of cases. During follow-up, 9% of patients developed recurrence. The 5-year overall survival rate was 70% and the 5-year disease-free survival rate was 85% These results seem to indicate that properly planned endoscopic CFR may be a valid alternative to traditional open approaches for the management of malignancies of the anterior skull base. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  9. Modeling complex neuropsychiatric disorders with human induced pluripotent stem cells.

    PubMed

    Tobe, Brian T D; Snyder, Evan Y; Nye, Jeffrey S

    2011-10-01

    Identifying the molecular and cellular basis of complex neuropsychiatric disorders (cNPDs) has been limited by the inaccessibility of central neurons, variability within broad diagnostic classifications, and the interplay of genetic and environmental factors. Recent work utilizing neuronally differentiated human induced pluripotent stem cells (hiPSCs) from Mendelian and polygenic cNPDs is beginning to illuminate neuritic, synaptic or cell body variations accompanied by specific gene or protein expression alterations largely mimicking known pathology. In some cases, phenotypes have only emerged after application of cellular stress or long duration of differentiation. Pathological and cellular expression features are fully or partially responsive to pharmacological treatment highlighting the potential utility of differentiated hiPSCs for discovery of personalized therapeutics and for identifying pathogenetically relevant targets in subgroups of patients within a broad syndromic classification. Because of the inherent variability in developing and differentiating hiPSC lines and the multiple comparisons implicit in 'omics' technologies, rigorous algorithms for assuring statistical significance and independent confirmation of results, will be required for robust modeling of cNPDs.

  10. Peroxisome biogenesis and human peroxisome-deficiency disorders

    PubMed Central

    FUJIKI, Yukio

    2016-01-01

    Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders (PBDs) including Zellweger syndrome, more than a dozen different complementation groups of Chinese hamster ovary (CHO) cell mutants impaired in peroxisome biogenesis are isolated as a model experimental system. By taking advantage of rapid functional complementation assay of the CHO cell mutants, successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs. Peroxins are divided into three groups: 1) peroxins including Pex3p, Pex16p and Pex19p, are responsible for peroxisome membrane biogenesis via Pex19p- and Pex3p-dependent class I and Pex19p- and Pex16p-dependent class II pathways; 2) peroxins that function in matrix protein import; 3) those such as Pex11pβ are involved in peroxisome division where DLP1, Mff, and Fis1 coordinately function. PMID:27941306

  11. The genetics of disorders of sex development in humans.

    PubMed

    Ohnesorg, Thomas; Vilain, Eric; Sinclair, Andrew H

    2014-01-01

    One of the defining events during human embryonic development with the most far-reaching effects for the individual is whether the embryo develops as male or female. The crucial step in this process is the differentiation of the bipotential embryonic gonads into either testes or ovaries. If the embryo inherits X and Y sex chromosomes, the Y-linked SRY (sex determining region in Y) gene initiates a network of genes that results in a functional testis and ultimately a male phenotype. By contrast, in an embryo with 2 X chromosomes, the undifferentiated gonad develops as an ovary resulting in a female phenotype. Perturbation of any of the genes in either the testicular or ovarian developmental pathway can result in individuals with disorders of sex development. In this review, we provide a summary of known components of testicular or ovarian pathways and their antagonistic actions and give a brief overview of new technologies currently used to identify the missing pieces of the sex development network.

  12. Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome

    PubMed Central

    Schad, Eva; Kalmar, Lajos; Tompa, Peter

    2013-01-01

    A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic structural disorder may be another key element because disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and structural disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of structural disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly disordered regions (>70% predicted disorder). Alternatively spliced symmetric exons tend to correspond to the most disordered regions. The genes of mostly disordered proteins (>70% predicted disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. SH3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain disordered modules have been particularly effective in exon-shuffling events. Our observations suggest that structural disorder has facilitated modular assembly of complex genes in evolution of the human genome. PMID:23460204

  13. Using the 3D Facial Norms Database to investigate craniofacial sexual dimorphism in healthy children, adolescents, and adults.

    PubMed

    Kesterke, Matthew J; Raffensperger, Zachary D; Heike, Carrie L; Cunningham, Michael L; Hecht, Jacqueline T; Kau, Chung How; Nidey, Nichole L; Moreno, Lina M; Wehby, George L; Marazita, Mary L; Weinberg, Seth M

    2016-01-01

    Although craniofacial sex differences have been extensively studied in humans, relatively little is known about when various dimorphic features manifest during postnatal life. Using cross-sectional data derived from the 3D Facial Norms data repository, we tested for sexual dimorphism of craniofacial soft-tissue morphology at different ages. One thousand five hundred fifty-five individuals, pre-screened for craniofacial conditions, between 3 and 25 years of age were placed in to one of six age-defined categories: early childhood, late childhood, puberty, adolescence, young adult, and adult. At each age group, sex differences were tested by ANCOVA for 29 traditional soft-tissue anthropometric measurements collected from 3D facial scans. Additionally, sex differences in shape were tested using a geometric morphometric analysis of 24 3D facial landmarks. Significant (p < 0.05) sex differences were observed in every age group for measurements covering multiple aspects of the craniofacial complex. The magnitude of the dimorphism generally increased with age, with large spikes in the nasal, cranial, and facial measurements observed after puberty. Significant facial shape differences (p < 0.05) were also seen at each age, with some dimorphic features already present in young children (eye fissure inclination) and others emerging only after puberty (mandibular position). Several craniofacial soft-tissue sex differences were already present in the youngest age group studied, indicating that these differences emerged prior to 3 years of age. The results paint a complex and heterogeneous picture, with different groups of traits exhibiting distinct patterns of dimorphism during ontogeny. The definitive adult male and female facial shape was present following puberty, but arose from numerous distinct changes taking place at earlier stages.

  14. 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.

  15. Zebrafish Craniofacial Development: A Window into Early Patterning.

    PubMed

    Mork, Lindsey; Crump, Gage

    2015-01-01

    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. © 2015 Elsevier Inc. All rights reserved.

  16. 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

  17. 76 FR 30370 - National Institute of Dental and Craniofacial Research; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ... Institute of Dental and Craniofacial Research; Meeting Notice of Closed Meeting Pursuant to section 10(d) of... Institute of Dental and Craniofacial Research Special Emphasis Panel; NIDCR Teleconference Review of...

  18. The Contributions of the Ribosome Biogenesis Protein Utp5/WDR43 to Craniofacial Development.

    PubMed

    Sondalle, S B; Baserga, S J; Yelick, P C

    2016-10-01

    Fairly recently, it was recognized that human ribosomopathies-developmental defects caused by mutations in ribosome biogenesis proteins-can exhibit tissue-specific defects rather than the expected global defects. This apparent anomaly-that seemingly ubiquitously expressed and required ribosomal proteins can have distinct functions in cell and tissue differentiation-has spurred new areas of research focused on better understanding translational mechanisms, biogenesis, and function in diverse cell types. This renewed appreciation for, and need to better understand, roles for ribosomal proteins in human development and disease has identified surprising similarities and differences in a variety of human ribosomopathies. Here, we discuss ribosomal protein functions in health and disease, focusing on the ribosome biogenesis protein Utp5/WDR43. New and exciting research in this field is anticipated to provide insight into a variety of previously understudied craniofacial dysostoses and result in significantly improved knowledge and understanding of roles for translational machinery in human craniofacial development and disease. © International & American Associations for Dental Research 2016.

  19. Evaluation of craniofacial morphology in patients with obstructive sleep apnea using lateral cephalometry and dynamic MRI.

    PubMed

    Bharadwaj, Rekha; Ravikumar, A; Krishnaswamy, N R

    2011-01-01

    Obstructive sleep apnea (OSA) is a potentially life-threatening disorder, characterized by repeated collapse of the upper airway during sleep with cessation of breathing. The altered mouth breathing produces morphological changes in craniofacial region. This study was designed to compare and validate the craniofacial morphological characteristics in patients with OSA using lateral cephalometry and to investigate the dentofacial characteristics of patients with OSA with respect to the obstructive sites determined by dynamic magnetic resonance imaging (MRI) to more accurately clarify the pathophysiological features. 10 patients with OSA were divided into two groups of five each according to their obstructive site determined by dynamic MRI. (1) Obstruction at the retropalatal and retroglossal region (Rp + Rg group) and (2) obstruction at the retropalatal region (Rp group). Lateral cephalogram both in upright and supine position was taken for all the subjects. In addition, dynamic MRI was performed to identify the sites of obstruction of the upper airway. Independent t-test was performed to evaluate the significant difference in the upright cephalometric variables between the study and control group and between the two groups. The changes in skeletal and soft tissue parameters with change in posture was assessed within the study and control group by paired t test. P value of ≤ 0.05 was considered as statistically significant. The study indicated that the first group of patients with both retropalatal and retroglossal obstruction showed signs of skeletal discrepancy that predisposed to obstruction at the retroglossal level and the soft tissue components like the soft palate and tongue that contributed to retropalatal obstruction. However, the second group of patients with only retropalatal obstruction had primarily soft tissue components associated with increased BMI that contributed to retropalatal obstruction. Evaluation of craniofacial morphology in OSA patients is

  20. Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders.

    PubMed

    Sanford, Mark

    2014-08-01

    Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.

  1. Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning.

    PubMed

    Muszkat, Mauro; de Mello, Claudia Berlim; Muñoz, Patricia de Oliveira Lima; Lucci, Tania Kiehl; David, Vinicius Frayze; Siqueira, José de Oliveira; Otta, Emma

    2015-01-01

    This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye-tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders.

  2. Face Scanning in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder: Human Versus Dog Face Scanning

    PubMed Central

    Muszkat, Mauro; de Mello, Claudia Berlim; Muñoz, Patricia de Oliveira Lima; Lucci, Tania Kiehl; David, Vinicius Frayze; Siqueira, José de Oliveira; Otta, Emma

    2015-01-01

    This study used eye tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and typical development (TD). Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye-tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders. PMID:26557097

  3. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders

    PubMed Central

    Gurwitz, David

    2016-01-01

    The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research. PMID:27757061

  4. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders.

    PubMed

    Gurwitz, David

    2016-09-01

    The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

  5. Exocrine pancreatic disorders in transsgenic mice expressing human keratin 8

    PubMed Central

    Casanova, M. Llanos; Bravo, Ana; Ramírez, Angel; Escobar, Gabriela Morreale de; Were, Felipe; Merlino, Glenn; Vidal, Miguel; Jorcano, José L.

    1999-01-01

    Keratins K8 and K18 are the major components of the intermediate-filament cytoskeleton of simple epithelia. Increased levels of these keratins have been correlated with various tumor cell characteristics, including progression to malignancy, invasive behavior, and drug sensitivity, although a role for K8/K18 in tumorigenesis has not yet been demonstrated. To examine the function of these keratins, we generated mice expressing the human K8 (hk8) gene, which leads to a moderate keratin-content increase in their simple epithelia. These mice displayed progressive exocrine pancreas alterations, including dysplasia and loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine by adipose tissue, as well as increased cell proliferation and apoptosis. Histological changes were not observed in other simple epithelia, such as the liver. Electron microscopy showed that transgenic acinar cells have keratins organized in abundant filament bundles dispersed throughout the cytoplasm, in contrast to control acinar cells, which have scarce and apically concentrated filaments. The phenotype found was very similar to that reported for transgenic mice expressing a dominant-negative mutant TGF-β type II receptor (TGFβRII mice). We show that these TGFβRII mutant mice also have elevated K8/K18 levels. These results indicate that simple epithelial keratins play a relevant role in the regulation of exocrine pancreas homeostasis and support the idea that disruption of mechanisms that normally regulate keratin expression in vivo could be related to inflammatory and neoplastic pancreatic disorders. PMID:10359568

  6. Computational Biomechanics of Human Red Blood Cells in Hematological Disorders.

    PubMed

    Li, Xuejin; Li, He; Chang, Hung-Yu; Lykotrafitis, George; Em Karniadakis, George

    2017-02-01

    We review recent advances in multiscale modeling of the biomechanical characteristics of red blood cells (RBCs) in hematological diseases, and their relevance to the structure and dynamics of defective RBCs. We highlight examples of successful simulations of blood disorders including malaria and other hereditary disorders, such as sickle-cell anemia, spherocytosis, and elliptocytosis.

  7. Computational models of oral and craniofacial development, growth, and repair.

    PubMed

    Hammond, P; Hutton, T; Maheswaran, S; Modgil, S

    2003-12-01

    This paper illustrates how biological and clinical problems stimulate research in biomedical informatics and how such research contributes to their solution. The computational models described use techniques from Logic Programming, Machine Learning, Computer Vision, and Biomathematics. They address problems in the development, growth, and repair of oral and craniofacial tissues arising in cell biology, clinical genetics, and dentistry. At the micro-level, the dynamic interaction of cells in the oral epithelium is modeled. At the macro-level, models are constructed of either the craniofacial shape of an individual or the craniofacial shape differences within and between healthy and congenitally abnormal populations. In between, in terms of scale, there are models of normal dentition and the use of computerized expert knowledge to guide the design of dental prostheses used to restore function in partially edentulous patients.

  8. Vagus nerve pain referred to the craniofacial region. A case report and literature review with implications for referred cardiac pain.

    PubMed

    Myers, D E

    2008-02-23

    The pain of angina pectoris and myocardial infarction is sometimes referred to the head and neck region. The mechanism for this effect remains obscure. A case is presented here that reports that electrical stimulation of a cardiac branch of the left vagus nerve in humans can cause referred craniofacial pain. This leads to the hypothesis that the vagus nerve plays a role in mediating this pain. A review of the clinical and physiologic literature supports this hypothesis.

  9. Psychiatric disorders biochemical pathways unraveled by human brain proteomics.

    PubMed

    Saia-Cereda, Verônica M; Cassoli, Juliana S; Martins-de-Souza, Daniel; Nascimento, Juliana M

    2017-02-01

    Approximately 25 % of the world population is affected by a mental disorder at some point in their life. Yet, only in the mid-twentieth century a biological cause has been proposed for these diseases. Since then, several studies have been conducted toward a better comprehension of those disorders, and although a strong genetic influence was revealed, the role of these genes in disease mechanism is still unclear. This led most recent studies to focus on the molecular basis of mental disorders. One line of investigation that has risen in the post-genomic era is proteomics, due to its power of revealing proteins and biochemical pathways associated with biological systems. Therefore, this review compiled and analyzed data of differentially expressed proteins, which were found in postmortem brain studies of the three most prevalent psychiatric diseases: schizophrenia, bipolar disorder and major depressive disorders. Overviewing both the proteomic methods used in postmortem brain studies, the most consistent metabolic pathways found altered in these diseases. We have unraveled those disorders share about 21 % of proteins affected, and though most are related to energy metabolism pathways deregulation, the main differences found are 14-3-3-mediated signaling in schizophrenia, mitochondrial dysfunction in bipolar disorder and oxidative phosphorylation in depression.

  10. 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.

  11. Bleeding management for pediatric craniotomies and craniofacial surgery.

    PubMed

    Goobie, Susan M; Haas, Thorsten

    2014-07-01

    Pediatric patients when undergoing craniotomies and craniofacial surgery may potentially have significant blood loss. The amount and extent will be dictated by the nature of the surgical procedure, the proximity to major blood vessels, and the age, and weight of the patient. The goals should be to maintain hemodynamic stability and oxygen carrying capacity and to prevent and treat hyperfibrinolysis and dilutional coagulopathy. Over transfusion and transfusion-related side effects should be minimized. This article will highlight the pertinent considerations for managing massive blood loss in pediatric patients undergoing craniotomies and craniofacial surgery. North American and European guidelines for intraoperative administration of fluid and blood products will be discussed.

  12. An annotated history of craniofacial surgery and intentional cranial deformation.

    PubMed

    Goodrich, J T; Tutino, M

    2001-01-01

    The history of craniofacial surgery and the use of intentional cranial deformation is a long and varied one. Researching some of the earliest medical writings and reviews of early terracotta and stone figures from throughout the world clearly revealed that these two forms of treatment were widely extant. Intentional cranial deformation was used for a number of reasons including beautification, tribal identification, and social stature. The development of craniofacial surgery is a more modern practice and its historical evolution is reviewed in the context of techniques and the personalities involved.

  13. Obstructive sleep apnoea in children with craniofacial syndromes

    PubMed Central

    Cielo, Christopher M.

    2014-01-01

    Summary Obstructive sleep apnoea syndrome (OSAS) is common in children. Craniofacial anomalies such as cleft palate are among the most common congenital conditions. Children with a variety of craniofacial conditions, including cleft palate, micrognathia, craniosynostosis, and midface hypoplasia are at increased risk for OSAS. Available evidence, which is largely limited to surgical case series and retrospective studies, suggests that OSAS can be successfully managed in these children through both surgical and non-surgical techniques. Prospective studies using larger cohorts of patients and including polysomnograms are needed to better understand the risk factors for this patient population and the efficacy of treatment options for OSAS and their underlying conditions. PMID:25555676

  14. Neutral versus Emotional Human Stimuli Processing in Children with Pervasive Developmental Disorders not Otherwise Specified

    ERIC Educational Resources Information Center

    Vannetzel, Leonard; Chaby, Laurence; Cautru, Fabienne; Cohen, David; Plaza, Monique

    2011-01-01

    Pervasive developmental disorder not otherwise specified (PDD-NOS) represents up to two-thirds of autism spectrum disorders; however, it is usually described in terms of the symptoms not shared by autism. The study explores processing of neutral and emotional human stimuli (by auditory, visual and multimodal channels) in children with PDD-NOS (n =…

  15. Craniofacial Ciliopathies Reveal Specific Requirements for GLI Proteins during Development of the Facial Midline

    PubMed Central

    Chang, Ching-Fang; Brugmann, Samantha A.

    2016-01-01

    Ciliopathies represent a broad class of disorders that affect multiple organ systems. The craniofacial complex is among those most severely affected when primary cilia are not functional. We previously reported that loss of primary cilia on cranial neural crest cells, via a conditional knockout of the intraflagellar transport protein KIF3a, resulted in midfacial widening due to a gain of Hedgehog (HH) activity. Here, we examine the molecular mechanism of how a loss of primary cilia can produce facial phenotypes associated with a gain of HH function. We show that loss of intraflagellar transport proteins (KIF3a or IFT88) caused aberrant GLI processing such that the amount of GLI3FL and GLI2FL was increased, thus skewing the ratio of GLIFL to GLIR in favor of the FL isoform. Genetic addition of GLI3R partially rescued the ciliopathic midfacial widening. Interestingly, despite several previous studies suggesting midfacial development relies heavily on GLI3R activity, the conditional loss of GLI3 alone did not reproduce the ciliopathic phenotype. Only the combined loss of both GLI2 and GLI3 was able to phenocopy the ciliopathic midfacial appearance. Our findings suggest that ciliopathic facial phenotypes are generated via loss of both GLI3R and GLI2R and that this pathology occurs via a de-repression mechanism. Furthermore, these studies suggest a novel role for GLI2R in craniofacial development. PMID:27802276

  16. The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development.

    PubMed

    Sperry, Ethan D; Hurd, Elizabeth A; Durham, Mark A; Reamer, Elyse N; Stein, Adam B; Martin, Donna M

    2014-09-01

    Heterozygous mutations in the chromatin remodeling gene CHD7 cause CHARGE syndrome, a developmental disorder with variable craniofacial dysmorphisms and respiratory difficulties. The molecular etiologies of these malformations are not well understood. Homozygous Chd7 null mice die by E11, whereas Chd7(Gt/+) heterozygous null mice are a viable and excellent model of CHARGE. We explored skeletal phenotypes in Chd7(Gt/+) and Chd7 conditional knockout mice, using Foxg1-Cre to delete Chd7 (Foxg1-CKO) in the developing eye, ear, nose, pharyngeal pouch, forebrain, and gut and Wnt1-Cre (Wnt1-CKO) to delete Chd7 in migrating neural crest cells. Foxg1-CKO mice exhibited postnatal respiratory distress and death, dysplasia of the eye, concha, and frontal bone, hypoplastic maxillary shelves and nasal epithelia, and reduced tracheal rings. Wnt1-CKO mice exhibited frontal and occipital bone dysplasia, hypoplasia of the maxillary shelves and mandible, and cleft palate. In contrast, heterozygous Chd7(Gt/+) mice had apparently normal skeletal development. Conditional deletion of Chd7 in ectodermal and endodermal derivatives (Foxg1-Cre) or migrating neural crest cells (Wnt1-Cre) results in varied and more severe craniofacial defects than in Chd7(Gt/+) mice. These studies indicate that CHD7 has an important, dosage-dependent role in development of several different craniofacial tissues. © 2014 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

  17. A computerized tomography study of the morphological interrelationship between the temporal bones and the craniofacial complex

    PubMed Central

    Costa, Helder Nunes; Slavicek, Rudolf; Sato, Sadao

    2012-01-01

    The hypothesis that the temporal bones are at the center of the dynamics of the craniofacial complex, directly influencing facial morphology, has been put forward long ago. This study examines the role of the spatial positioning of temporal bones (frontal and sagittal inclination) in terms of influencing overall facial morphology. Several 3D linear, angular and orthogonal measurements obtained through computerized analysis of virtual models of 163 modern human skulls reconstructed from cone-beam computed tomography images were analyzed and correlated. Additionally, the sample was divided into two subgroups based on the median value of temporal bone sagittal inclination [anterior rotation group (n = 82); posterior rotation group (n = 81)], and differences between groups evaluated. Correlation coefficients showed that sagittal inclination of the temporal bone was significantly (P < 0.01) related to midline flexion, transversal width and anterior–posterior length of the basicranium, to the anterior–posterior positioning of the mandible and maxilla, and posterior midfacial height. Frontal inclination of the temporal bone was significantly related (P < 0.01) to basicranium anterior–posterior and transversal dimensions, and to posterior midfacial height. In comparison with the posterior rotation group, the anterior rotation group presented a less flexed and anterior–posteriorly longer cranial base, a narrower skull, porion and the articular eminence located more superiorly and posteriorly, a shorter posterior midfacial height, the palatal plane rotated clockwise, a more retrognathic maxilla and mandible, and the upper posterior occlusal plane more inclined and posteriorly located. The results suggest that differences in craniofacial morphology are highly integrated with differences in the positional relationship of the temporal bones. The sagittal inclination of the temporal bone seems to have a greater impact on the 3D morphology of the craniofacial complex than

  18. Exclusion of the PAX2 gene as a candidate gene for Crouzon craniofacial dysostosis

    SciTech Connect

    Preston, R.A.; Gorry, M.C.; Warman, M.

    1994-09-01

    Crouzon craniofacial dysostosis (CFD, MIM 123500) is an abnormality of craniofacial development characterized by premature craniosynostosis, maxillary hypoplasia, and shallow orbits. We have mapped the CFD gene locus using a candidate gene approach to a 7 centiMorgan region on chromosome 10q in three CFD families. A maximal multipoint LOD score of 12.33 was achieved for a locus 2 cM distal to the microsatellite marker D10S209. A comparison of several physical, cytogenetic, and linkage maps revealed that the cytogenetic bands, 10q25-q26, most likely contain this CFD locus. The PAX2 gene, which has been mapped near another marker which in turn has been mapped to 10q25, was analyzed as a candidate gene. PAX2 was chosen for analysis because mutations in other members of the PAX gene family have been identified with human craniofacial abnormalities (e.g. Waardenburg syndrome). A YAC contig, consisting of 5 overlapping groups and composed of 11 YACs that spans the entire 7 cM region, was assembled for PAX2 analyses. None of these YACs supported PAX2-specific amplification using primer sets for both the second and third PAX2 exons. Control amplifications for YAC vector sequences produced robust amplifications in all cases. In addition, SSCP analyses of amplification products generated from the second and third PAX2 exons and the 3{prime} untranslated region of the PAX2 gene from both affected and unaffected family members in two of the kindreds failed to reveal any polymorphisms. Although it remains theoretically possible, due to artifacts in the YAC contigs, it is unlikely that PAX2 is the CFD gene.

  19. Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies

    PubMed Central

    Ashe, Alyson; Butterfield, Natalie C.; Town, Liam; Courtney, Andrew D.; Cooper, Ashley N.; Ferguson, Charles; Barry, Rachael; Olsson, Fredrik; Liem, Karel F.; Parton, Robert G.; Wainwright, Brandon J.; Anderson, Kathryn V.; Whitelaw, Emma; Wicking, Carol

    2012-01-01

    Mutations in components of the intraflagellar transport (IFT) machinery required for assembly and function of the primary cilium cause a subset of human ciliopathies characterized primarily by skeletal dysplasia. Recently, mutations in the IFT-A gene IFT144 have been described in patients with Sensenbrenner and Jeune syndromes, which are associated with short ribs and limbs, polydactyly and craniofacial defects. Here, we describe an N-ethyl-N-nitrosourea-derived mouse mutant with a hypomorphic missense mutation in the Ift144 gene. The mutant twinkle-toes (Ift144twt) phenocopies a number of the skeletal and craniofacial anomalies seen in patients with human skeletal ciliopathies. Like other IFT-A mouse mutants, Ift144 mutant embryos display a generalized ligand-independent expansion of hedgehog (Hh) signalling, in spite of defective ciliogenesis and an attenuation of the ability of mutant cells to respond to upstream stimulation of the pathway. This enhanced Hh signalling is consistent with cleft palate and polydactyly phenotypes in the Ift144twt mutant, although extensive rib branching, fusion and truncation phenotypes correlate with defects in early somite patterning and may reflect contributions from multiple signalling pathways. Analysis of embryos harbouring a second allele of Ift144 which represents a functional null, revealed a dose-dependent effect on limb outgrowth consistent with the short-limb phenotypes characteristic of these ciliopathies. This allelic series of mouse mutants provides a unique opportunity to uncover the underlying mechanistic basis of this intriguing subset of ciliopathies. PMID:22228095

  20. The questionable contribution of the Neolithic and the Bronze Age to European craniofacial form

    PubMed Central

    Brace, C. Loring; Seguchi, Noriko; Quintyn, Conrad B.; Fox, Sherry C.; Nelson, A. Russell; Manolis, Sotiris K.; Qifeng, Pan

    2006-01-01

    Many human craniofacial dimensions are largely of neutral adaptive significance, and an analysis of their variation can serve as an indication of the extent to which any given population is genetically related to or differs from any other. When 24 craniofacial measurements of a series of human populations are used to generate neighbor-joining dendrograms, it is no surprise that all modern European groups, ranging all of the way from Scandinavia to eastern Europe and throughout the Mediterranean to the Middle East, show that they are closely related to each other. The surprise is that the Neolithic peoples of Europe and their Bronze Age successors are not closely related to the modern inhabitants, although the prehistoric/modern ties are somewhat more apparent in southern Europe. It is a further surprise that the Epipalaeolithic Natufian of Israel from whom the Neolithic realm was assumed to arise has a clear link to Sub-Saharan Africa. Basques and Canary Islanders are clearly associated with modern Europeans. When canonical variates are plotted, neither sample ties in with Cro-Magnon as was once suggested. The data treated here support the idea that the Neolithic moved out of the Near East into the circum-Mediterranean areas and Europe by a process of demic diffusion but that subsequently the in situ residents of those areas, derived from the Late Pleistocene inhabitants, absorbed both the agricultural life way and the people who had brought it. PMID:16371462

  1. Convergent integration of animal model and human studies of bipolar disorder (manic-depressive illness).

    PubMed

    Le-Niculescu, Helen; Patel, Sagar D; Niculescu, Alexander B

    2010-10-01

    Animal models and human studies of bipolar disorder and other psychiatric disorders are becoming increasingly integrated, prompted by recent successes. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit-to-disease way of extracting reproducible and biologically important signal, in sharp contrast to the fit-to-cohort effect, disappointing findings to date, and limited reproducibility of human genetic analyses alone. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer biology and diabetes.

  2. Human consensus interferons: Bridging the natural and artificial cytokines with intrinsic disorder.

    PubMed

    El-Baky, Nawal Abd; Uversky, Vladimir N; Redwan, Elrashdy M

    2015-12-01

    The consensus interferons are artificially engineered proteins that combine most of the therapeutic features of natural human α-interferons and show high anti-cancer and anti-viral activities. Egyptian patients infected with hepatitis C virus (HCV) genotype 4 show lower responses to interferon (IFN) therapy than the distributed worldwide patients infected with the other HCV genotypes. Numerous studies have reported that patients with hepatitis C who have not responded to a previous standard IFN-alpha therapy or those who relapsed following treatment cessation may benefit from retreatment with consensus IFN-α (cIFN-α). IFNs-α are shown here to have functionally important disordered regions. Furthermore, a strong correlation is established between the peculiarities of disorder profiles of these proteins and their known structural features. Intrinsic disorder profiles of existing cIFNs-α possess remarkable similarity to the consensus disorder profile calculated as averaged disorder predispositions of all human IFNs-α. If the peculiarities of disorder distribution within the protein sequence are related to protein functionality, then comparison of the disorder profiles of artificial cIFNs (query profiles) with the averaged disorder predisposition profile of human IFNs-α (target profile) can be used in the design of novel cIFNs. The goal here would be to achieve a close similarity between the query and target profiles by manipulating the cIFN sequence. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Craniofacial birth defects: The role of neural crest cells in the etiology and pathogenesis of Treacher Collins syndrome and the potential for prevention.

    PubMed

    Trainor, Paul A

    2010-12-01

    Of all the babies born with birth defects, approximately one-third display anomalies of the head and face [Gorlin et al., 1990] including cleft lip, cleft palate, small or absent facial and skull bones and improperly formed nose, eyes, ears, and teeth. Craniofacial disorders are a primary cause of infant mortality and have serious lifetime functional, esthetic, and social consequences that are devastating to both children and parents alike. Comprehensive surgery, dental care, psychological counseling, and rehabilitation can help ameliorate-specific problems but at great cost over many years which dramatically affects national health care budgets. For example, the Center for Disease Control and Prevention estimates that the lifetime cost of treating the children born each year with cleft lip and/or cleft palate alone to be US$697 million. Treating craniofacial malformations, of which in excess of 700 distinct syndromes have been described, through comprehensive, well-coordinated and integrated strategies can provide satisfactory management of individual conditions, however, the results are often variable and rarely fully corrective. Therefore, better techniques for tissue repair and regeneration need to be developed and therapeutic avenues of prevention need to be explored in order to eliminate the devastating consequences of head and facial birth defects. To do this requires a thorough understanding of the normal events that control craniofacial development during embryogenesis. This review therefore focuses on recent advances in our understanding of the basic etiology and pathogenesis of a rare craniofacial disorder known as Treacher Collins syndrome and emerging prospects for prevention that may have broad application to congenital craniofacial birth defects.

  4. Craniofacial Birth Defects: The Role of Neural Crest Cells in the Etiology and Pathogenesis of Treacher Collins Syndrome and the Potential for Prevention

    PubMed Central

    Trainor, Paul A.

    2013-01-01

    Of all the babies born with birth defects, approximately one-third display anomalies of the head and face [Gorlin et al., 1990] including cleft lip, cleft palate, small or absent facial and skull bones and improperly formed nose, eyes, ears, and teeth. Craniofacial disorders are a primary cause of infant mortality and have serious lifetime functional, esthetic, and social consequences that are devastating to both children and parents alike. Comprehensive surgery, dental care, psychological counseling, and rehabilitation can help ameliorate-specific problems but at great cost over many years which dramatically affects national health care budgets. For example, the Center for Disease Control and Prevention estimates that the lifetime cost of treating the children born each year with cleft lip and/or cleft palate alone to be US$697 million. Treating craniofacial malformations, of which in excess of 700 distinct syndromes have been described, through comprehensive, well-coordinated and integrated strategies can provide satisfactory management of individual conditions, however, the results are often variable and rarely fully corrective. Therefore, better techniques for tissue repair and regeneration need to be developed and therapeutic avenues of prevention need to be explored in order to eliminate the devastating consequences of head and facial birth defects. To do this requires a thorough understanding of the normal events that control craniofacial development during embryogenesis. This review therefore focuses on recent advances in our understanding of the basic etiology and pathogenesis of a rare craniofacial disorder known as Treacher Collins syndrome and emerging prospects for prevention that may have broad application to congenital craniofacial birth defects. PMID:20734335

  5. 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.

  6. Hutchinson-Gilford progeria syndrome: Oral and craniofacial phenotypes

    PubMed Central

    Domingo, D.L.; Trujillo, M.I.; Council, S.E.; Merideth, M.A.; Gordon, L.B.; Wu, T.; Introne, W.J.; Gahl, W.A.; Hart, T.C.

    2008-01-01

    OBJECTIVE Hutchinson-Gilford progeria syndrome (HGPS) is a rare early-onset accelerated senescence syndrome. In HGPS, a recently identified de novo dominant mutation of the lamin A gene (LMNA) produces abnormal lamin A, resulting in compromised nuclear membrane integrity. Clinical features include sclerotic skin, cardiovascular and bone abnormalities, and marked growth retardation. Craniofacial features include “bird-like” facies, alopecia, craniofacial disproportion and dental crowding. Our prospective study describes dental, oral soft tissue, and craniofacial bone features in HGPS. METHODS Fifteen patients with confirmed p.G608G LMNA mutation (1–17 years, 7 males, 8 females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones and dentition were identified. RESULTS Radiographic findings included hypodontia (n=7), dysmorphic teeth (n=5), steep mandibular angles (n=11), and thin basal bone (n=11). Soft tissue findings included ogival palatal arch (n=8), median sagittal palatal fissure (n=7), and ankyloglossia (n=7). Calculated dental ages (9months–11y2m) were significantly lower than chronological ages (1y6m–17y8m) (p=0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms. CONCLUSION Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS. PMID:19236595

  7. Trigeminal branch stimulation for the treatment of intractable craniofacial pain.

    PubMed

    Ellis, Jason A; Mejia Munne, Juan C; Winfree, Christopher J

    2015-07-01

    OBJECT Trigeminal branch stimulation has been used in the treatment of craniofacial pain syndromes. The risks and benefits of such an approach have not been clearly delineated in large studies, however. The authors report their experience in treating craniofacial pain with trigeminal branch stimulation and share the lessons they have learned after 93 consecutive electrode placements. METHODS A retrospective review of all patients who underwent trigeminal branch electrode placement by the senior author (C.J.W.) for the treatment of craniofacial pain was performed. RESULTS Thirty-five patients underwent implantation of a total of 93 trial and permanent electrodes between 2006 and 2013. Fifteen patients who experienced improved pain control after trial stimulation underwent implantation of permanent stimulators and were followed for an average of 15 months. At last follow-up 73% of patients had improvement in pain control, whereas only 27% of patients had no pain improvement. No serious complications were seen during the course of this study. CONCLUSIONS Trigeminal branch stimulation is a safe and effective treatment for a subset of patients with intractable craniofacial pain.

  8. Analysis of the 50 most cited papers in craniofacial surgery.

    PubMed

    Tahiri, Youssef; Fleming, Tara M; Greathouse, Travis; Tholpady, Sunil S

    2015-12-01

    The intent of this study is to discuss the most prominent literature in craniofacial surgery. To do so, using the ISI Web of Science, a ranking by average number of citations per year of the top 50 craniofacial surgery articles was compiled. All plastic surgery journals listed in the "Surgery" category in the ISI Web of Knowledge Journal Citation Reports 2013 Science Edition were considered. Journal of publication, country of origin, collaborating institutions, topic of interest, and level of evidence were analyzed. The total number of citations ranged from 47 to 1017. Average number of citations per year ranged from 46.2 to 8.6. The oldest article in the top 50 was published in 1988 and the most recent in 2009. The majority of the articles came from Plastic and Reconstructive Surgery with 28 of the 50. The majority of the articles, originated from the United States (56%). Reconstruction of acquired defects was the most commonly examined topic at 46.2%; followed by articles discussing reconstruction of congenital defects (23.1%). The most common level of evidence was level 3. This extensive examination of the craniofacial literature highlights the important part that craniofacial surgery takes in the field of plastic surgery.

  9. [Mental disorders in patients infected with the human immunodeficiency virus].

    PubMed

    Gallego Deike, L; Gordillo Alvarez-Valdés, M V

    2001-11-01

    The present review aims to offer a concise of information about the diverse mental disorders affecting HIV-infected patients. Although most studies coincide in remarking that HIV-infected patients are frequently burden with psychological distress, the prevalence of the different mental disorders being present at the time of evaluation is widely variable. HIV infection clinical stage, prior psychiatric morbidity, and sociodemographic issues are also related to the type and risk for mental disorders. When planning therapeutic interventions, psychopharmacological or psychological, for HIV-infected patients several peculiarities should be taken into account. The accurate psychosocial evaluation and prompt therapeutic intervention, could help to reduce psychiatric-psychologic morbidity in a population of patients with multifactorial impairment in their quality of life and improve the adherence to treatment.

  10. 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.

  11. Craniofacial pain and jaw-muscle activity during sleep.

    PubMed

    Yachida, W; Castrillon, E E; Baad-Hansen, L; Jensen, R; Arima, T; Tomonaga, A; Ohata, N; Svensson, P

    2012-06-01

    This study compared the jaw-muscle electromyographic (EMG) activity during sleep in patients with craniofacial pain (n = 63) or no painful conditions (n = 52) and between patients with tension-type headache (TTH: n = 30) and healthy control individuals (n = 30). All participants used a portable single-channel EMG device (Medotech A/S) for four nights. There was no significant difference in EMG activity between craniofacial pain (24.5 ± 17.9 events/hr) and no painful conditions (19.7 ± 14.5), or between TTH (20.8 ± 15.0) and healthy control individuals (15.2 ± 11.6, p >.050). There were positive correlations between EMG activity and number of painful muscles (r = 0.188; p = 0.044), characteristic pain intensity (r = 0.187; p = 0.046), McGill Pain Questionnaire (r = 0.251; p = 0.008), and depression scores (r = 0.291; p = 0.002). Patients with painful conditions had significantly higher night-to-night variability compared with pain-free individuals (p < 0.050). This short-term observational study suggests that there are no major differences between patients with different craniofacial pain conditions and pain-free individuals in terms of jaw-muscle EMG activity recorded with a single-channel EMG device during sleep. However, some associations may exist between the level of EMG activity and various parameters of craniofacial pain. Longitudinal studies are warranted to further explore the relationship between sleep bruxism and craniofacial pain.

  12. 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

    2017-03-29

    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.

  13. Human Sexual Desire Disorder: Do We Have a Problem?

    ERIC Educational Resources Information Center

    McNab, Warren L.; Henry, Jean

    2006-01-01

    Hypoactive Sexual Desire Disorder (HSDD), loss of sexual desire for sexual activity, is one of the most common sexual dysfunctions of men and women in the United States. This article presents an overview of this specific sexual dysfunction including incidence, possible causes, treatment options, and the role of the health educator in addressing…

  14. Emotion Recognition in Animated Compared to Human Stimuli in Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Brosnan, Mark; Johnson, Hilary; Grawmeyer, Beate; Chapman, Emma; Benton, Laura

    2015-01-01

    There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon…

  15. Emotion Recognition in Animated Compared to Human Stimuli in Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Brosnan, Mark; Johnson, Hilary; Grawmeyer, Beate; Chapman, Emma; Benton, Laura

    2015-01-01

    There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon…

  16. Managing obstructive sleep apnoea in children: the role of craniofacial morphology.

    PubMed

    Bozzini, Maria Fernanda Rabelo; Di Francesco, Renata Cantisani

    2016-11-01

    Obstructive sleep apnoea syndrome is a type of sleep-disordered breathing that affects 1 to 5% of all children. Pharyngeal and palatine tonsil hypertrophy is the main predisposing factor. Various abnormalities are predisposing factors for obstructive sleep apnoea, such as decreased mandibular and maxillary lengths, skeletal retrusion, increased lower facial height and, consequently, increased total anterior facial height, a larger cranio-cervical angle, small posterior airway space and an inferiorly positioned hyoid bone. The diagnosis is based on the clinical history, a physical examination and tests confirming the presence and severity of upper airway obstruction. The gold standard test for diagnosis is overnight polysomnography. Attention must be paid to identify the craniofacial characteristics. When necessary, children should be referred to orthodontists and/or sleep medicine specialists for adequate treatment in addition to undergoing an adenotonsillectomy.

  17. Managing obstructive sleep apnoea in children: the role of craniofacial morphology

    PubMed Central

    Bozzini, Maria Fernanda Rabelo; Di Francesco, Renata Cantisani

    2016-01-01

    Obstructive sleep apnoea syndrome is a type of sleep-disordered breathing that affects 1 to 5% of all children. Pharyngeal and palatine tonsil hypertrophy is the main predisposing factor. Various abnormalities are predisposing factors for obstructive sleep apnoea, such as decreased mandibular and maxillary lengths, skeletal retrusion, increased lower facial height and, consequently, increased total anterior facial height, a larger cranio-cervical angle, small posterior airway space and an inferiorly positioned hyoid bone. The diagnosis is based on the clinical history, a physical examination and tests confirming the presence and severity of upper airway obstruction. The gold standard test for diagnosis is overnight polysomnography. Attention must be paid to identify the craniofacial characteristics. When necessary, children should be referred to orthodontists and/or sleep medicine specialists for adequate treatment in addition to undergoing an adenotonsillectomy. PMID:27982168

  18. Deciphering the cause of evolutionary variance within intrinsically disordered regions in human proteins.

    PubMed

    Banerjee, Sanghita; Chakraborty, Sandip; De, Rajat K

    2017-02-01

    Why the intrinsically disordered regions evolve within human proteome has became an interesting question for a decade. Till date, it remains an unsolved yet an intriguing issue to investigate why some of the disordered regions evolve rapidly while the rest are highly conserved across mammalian species. Identifying the key biological factors, responsible for the variation in the conservation rate of different disordered regions within the human proteome, may revisit the above issue. We emphasized that among the other biological features (multifunctionality, gene essentiality, protein connectivity, number of unique domains, gene expression level and expression breadth) considered in our study, the number of unique protein domains acts as a strong determinant that negatively influences the conservation of disordered regions. In this context, we justified that proteins having a fewer types of domains preferably need to conserve their disordered regions to enhance their structural flexibility which in turn will facilitate their molecular interactions. In contrast, the selection pressure acting on the stretches of disordered regions is not so strong in the case of multi-domains proteins. Therefore, we reasoned that the presence of conserved disordered stretches may compensate the functions of multiple domains within a single domain protein. Interestingly, we noticed that the influence of the unique domain number and expression level acts differently on the evolution of disordered regions from that of well-structured ones.

  19. Puberty as a Critical Risk Period for Eating Disorders: A Review of Human and Animal Studies

    PubMed Central

    Klump, Kelly L.

    2013-01-01

    Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. PMID:23998681

  20. Puberty as a critical risk period for eating disorders: a review of human and animal studies.

    PubMed

    Klump, Kelly L

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Association between latent toxoplasmosis and major depression, generalised anxiety disorder and panic disorder in human adults.

    PubMed

    Gale, Shawn D; Brown, Bruce L; Berrett, Andrew; Erickson, Lance D; Hedges, Dawson W

    2014-08-01

    Latent infection with the apicomplexan Toxoplasma gondii (Nicolle et Manceaux, 1908) has been associated with schizophrenia, bipolar disorder and self-harm behaviour. However, the potential relationship between T. gondii immunoglobulin G antibody (IgG) seropositivity and generalised-anxiety disorder (GAD) and panic disorder (PD) has not been investigated. The associations between serum reactivity to T. gondii and major depressive disorder (MDD), GAD and PD were evaluated in a total sample of 1 846 adult participants between the ages of 20 and 39 years from the United States Center for Disease Control's National Health and Nutrition Examination Survey (NHANES). Approximately 16% of the overall sample was seropositive for T. gondii and 7% of the sample met criteria for MDD, 2% for GAD and 2% for PD. There were no significant associations between T. gondii IgG seroprevalence and MDD (OR = 0.484, 95% CI = 0.186-1.258), GAD (OR = 0.737, 95% CI = 0.218-2.490) or PD (OR = 0.683, 95% CI = 0.206-2.270) controlling for sex, ethnicity, poverty-to-income ratio and educational attainment. However, limited evidence suggested a possible association between absolute antibody titres for T. gondii and GAD and PD but not MDD. Toxoplasma gondii seroprevalence was not associated with MDD, GAD or PD within the context of the limitations of this study, although there may be an association of T. gondii serointensity with and GAD and PD, which requires further study.

  2. Angiogenic and Osteogenic Potential of Bone Repair Cells for Craniofacial Regeneration

    PubMed Central

    Pagni, Giorgio; Park, Chan-Ho; Tarle, Susan A.; Bartel, Ronnda L.; Giannobile, William V.

    2010-01-01

    There has been increased interest in the therapeutic potential of bone marrow derived cells for tissue engineering applications. Bone repair cells (BRCs) represent a unique cell population generated via an ex vivo, closed-system, automated cell expansion process, to drive the propagation of highly osteogenic and angiogenic cells for bone engineering applications. The aims of this study were (1) to evaluate the in vitro osteogenic and angiogenic potential of BRCs, and (2) to evaluate the bone and vascular regenerative potential of BRCs in a craniofacial clinical application. BRCs were produced from bone marrow aspirates and their phenotypes and multipotent potential characterized. Flow cytometry demonstrated that BRCs were enriched for mesenchymal and vascular phenotypes. Alkaline phosphatase and von Kossa staining were performed to assess osteogenic differentiation, and reverse transcriptase–polymerase chain reaction was used to determine the expression levels of bone specific factors. Angiogenic differentiation was determined through in vitro formation of tube-like structures and fluorescent labeling of endothelial cells. Finally, 6 weeks after BRC transplantation into a human jawbone defect, a biopsy of the regenerated site revealed highly vascularized, mineralized bone tissue formation. Taken together, these data provide evidence for the multilineage and clinical potential of BRCs for craniofacial regeneration. PMID:20412009

  3. Mutations in Hedgehog acyltransferase (Hhat) perturb Hedgehog signaling, resulting in severe acrania-holoprosencephaly-agnathia craniofacial defects.

    PubMed

    Dennis, Jennifer F; Kurosaka, Hiroshi; Iulianella, Angelo; Pace, Jennifer; Thomas, Nancy; Beckham, Sharon; Williams, Trevor; Trainor, Paul A

    2012-01-01

    Holoprosencephaly (HPE) is a failure of the forebrain to bifurcate and is the most common structural malformation of the embryonic brain. Mutations in SHH underlie most familial (17%) cases of HPE; and, consistent with this, Shh is expressed in midline embryonic cells and tissues and their derivatives that are affected in HPE. It has long been recognized that a graded series of facial anomalies occurs within the clinical spectrum of HPE, as HPE is often found in patients together with other malformations such as acrania, anencephaly, and agnathia. However, it is not known if these phenotypes arise through a common etiology and pathogenesis. Here we demonstrate for the first time using mouse models that Hedgehog acyltransferase (Hhat) loss-of-function leads to holoprosencephaly together with acrania and agnathia, which mimics the severe condition observed in humans. Hhat is required for post-translational palmitoylation of Hedgehog (Hh) proteins; and, in the absence of Hhat, Hh secretion from producing cells is diminished. We show through downregulation of the Hh receptor Ptch1 that loss of Hhat perturbs long-range Hh signaling, which in turn disrupts Fgf, Bmp and Erk signaling. Collectively, this leads to abnormal patterning and extensive apoptosis within the craniofacial primordial, together with defects in cartilage and bone differentiation. Therefore our work shows that Hhat loss-of-function underscrores HPE; but more importantly it provides a mechanism for the co-occurrence of acrania, holoprosencephaly, and agnathia. Future genetic studies should include HHAT as a potential candidate in the etiology and pathogenesis of HPE and its associated disorders.

  4. Nasal septal and craniofacial form in European- and African-derived populations.

    PubMed

    Holton, Nathan E; Yokley, Todd R; Figueroa, Aaron

    2012-09-01

    As a component of the chondrocranium, the nasal septum influences the anteroposterior dimensions of the facial skeleton. The role of the septum as a facial growth center, however, has been studied primarily in long-snouted mammals, and its precise influence on human facial growth is not as well understood. Whereas the nasal septum may be important in the anterior growth of the human facial skeleton early in ontogeny, the high incidence of nasal septal deviation in humans suggests the septum's influence on human facial length is limited to the early phases of facial growth. Nevertheless, the nasal septum follows a growth trajectory similar to the facial skeleton and, as such, its prolonged period of growth may influence other aspects of facial development. Using computed tomography scans of living human subjects (n = 70), the goal of the present study is to assess the morphological relationship between the nasal septum and facial skeleton in European- and African-derived populations, which have been shown to exhibit early developmental differences in the nasal septal-premaxillary complex. First we assessed whether there is population variation in the size of the nasal septum in European- and African-derived samples. This included an evaluation of septal deviation and the spatial constraints that influence variation in this condition. Next, we assessed the relationship between nasal septal size and craniofacial shape using multivariate regression techniques. Our results indicate that there is significant population variation in septal size and magnitude of septal deviation, both of which are greater in the European-derived sample. While septal deviation suggests a disjunction between the nasal septum and other components of the facial skeleton, we nevertheless found a significant relationship between the size of the nasal septum and craniofacial shape, which appears to largely be a response to the need to accommodate variation in nasal septal size.

  5. Basonuclin 2 has a function in the multiplication of embryonic craniofacial mesenchymal cells and is orthologous to disco proteins

    PubMed Central

    Vanhoutteghem, Amandine; Maciejewski-Duval, Anna; Bouche, Cyril; Delhomme, Brigitte; Hervé, Françoise; Daubigney, Fabrice; Soubigou, Guillaume; Araki, Masatake; Araki, Kimi; Yamamura, Ken-ichi; Djian, Philippe

    2009-01-01

    Basonuclin 2 is a recently discovered zinc finger protein of unknown function. Its paralog, basonuclin 1, is associated with the ability of keratinocytes to multiply. The basonuclin zinc fingers are closely related to those of the Drosophila proteins disco and discorelated, but the relation between disco proteins and basonuclins has remained elusive because the function of the disco proteins in larval head development seems to have no relation to that of basonuclin 1 and because the amino acid sequence of disco, apart from the zinc fingers, also has no similarity to that of the basonuclins. We have generated mice lacking basonuclin 2. These mice die within 24 h of birth with a cleft palate and abnormalities of craniofacial bones and tongue. In the embryonic head, expression of the basonuclin 2 gene is restricted to mesenchymal cells in the palate, at the periphery of the tongue, and in the mesenchymal sheaths that surround the brain and the osteocartilagineous structures. In late embryos, the rate of multiplication of these mesenchymal cells is greatly diminished. Therefore, basonuclin 2 is essential for the multiplication of craniofacial mesenchymal cells during embryogenesis. Non-Drosophila insect databases available since 2008 reveal that the basonuclins and the disco proteins share much more extensive sequence and gene structure similarity than noted when only Drosophila sequences were examined. We conclude that basonuclin 2 is both structurally and functionally the vertebrate ortholog of the disco proteins. We also note the possibility that some human craniofacial abnormalities are due to a lack of basonuclin 2. PMID:19706529

  6. [To err is human? Interests of chaotic models to study adult psychiatric disorders and developmental disorders].

    PubMed

    Benarous, X; Cohen, D

    2016-02-01

    Many clinical and biological parameters have nonlinear chaotic fluctuations. These variations result in unexpected pseudo-random transitions. In these models, few risk factors can lead to unexpected phenomena if oscillations and self-reinforcement patterns occur. Complex rhythms could ease the ability of a physiological system to adapt and react quickly to a constantly changing environment. It has been proposed that several psychiatric disorders and developmental disorders are characterized by a loss of complex rhythm in favor of a more organized pattern. We examine evidence to support these assumptions in literatures. We performed a literature review of the main computerized databases (Medline, PubMed) and manual searches of the literature concerning non dynamic rhythms in time series analysis, in adults with psychiatric disorder and children with developmental disorder. These results were interpreted through a developmental approach that highlights the role of the learning process in the emergence of abilities. Analysis of clinical scores and electroencephalographic data have found that subjects with bipolar disorder or schizophrenia, tested over a time series, have lower chaotic rhythms compared with healthy subjects. Growing children share several properties of a complex system: the interdependence of developmental axes (motor, emotional, language, social skills), multiple hierarchical levels (i.e. genetic, biological, environmental, and cultural), the two-way transactions between the child and his environment, and the sensitivity to initial conditions. This could explain the difficulty to predict the emergence of abilities or the long-term prognosis of impairment in children. This limitation is not only due to errors in the explanatory model or the lack of explanatory variable. It is also caused by instability, which is a core characteristic of a chaotic system. The study of chaotic rhythms in time-series clinical and nonclinical data (e.g. EEG, functional

  7. Effects of tongue volume reduction on craniofacial growth

    PubMed Central

    Liu, Zi-Jun; Shcherbatyy, Volodymyr; Gu, Gaoman; Perkins, Jonathan A.

    2008-01-01

    The interaction between tongue size/volume and craniofacial skeletal growth is essential for understanding the mechanism of specific types of malocclusion and objectively measuring outcomes of various surgical and/or orthodontic treatments. Currently available information on this interaction is limited. This study was designed to examine how tongue body volume reduction affects craniofacial skeleton and dental arch formation during the rapid growth period in five 12-week-old Yucatan minipig sibling pairs. One of each pair received a standardized reduction glossectomy to reduce tongue volume by 15-17% (reduction group), and the other had the reduction glossectomy incisions without tissue removal (sham group). Before surgery, five stainless steel screws were implanted into standardized craniofacial skeletal locations. A series of cephalograms, lateral and axial, were obtained longitudinally at 1 week preoperative, and 2 and 4 weeks postoperative. These images were traced using superimposition, and linear and angular variables were measured digitally. Upon euthanasia, direct osteometric measurements were obtained from harvested skulls. Five en-bloc bone pieces were further cut for bone mineral examination by dual photon/energy X-ray absorptiometry (DEXA). The results indicate that: (1) while daily food consumption and weekly body weight were not significantly affected, tongue volume reduction showed an overall negative effect on the linear expansion of craniofacial skeletons; (2) premaxilla and mandibular symphysis lengths, and anterior dental arch width were significantly less in reduction than sham animals at 2 and/or 4 weeks after the surgery; (3) both premaxilla/maxilla and mandible bone mineral density and content were lower in reduction than sham animals, significantly lower in anterior mandible; (4) craniofacial skeletal and dental arch size were significantly smaller in reduction than sham animals, being most significant in the mandibular anterior length and

  8. The human microbiome in hematopoiesis and hematologic disorders

    PubMed Central

    Manzo, Veronica E.

    2015-01-01

    Humans are now understood to be in complex symbiosis with a diverse ecosystem of microbial organisms, including bacteria, viruses, and fungi. Efforts to characterize the role of these microorganisms, commonly referred as the microbiota, in human health have sought to answer the fundamental questions of what organisms are present, how are they functioning to interact with human cells, and by what mechanism are these interactions occurring. In this review, we describe recent efforts to describe the microbiota in healthy and diseased individuals, summarize the role of various molecular technologies (ranging from 16S ribosomal RNA to shotgun metagenomic sequencing) in enumerating the community structure of the microbiota, and explore known interactions between the microbiota and humans, with a focus on the microbiota’s role in hematopoiesis and hematologic diseases. PMID:26012569

  9. Synaptic dysregulation in a human iPS cell model of mental disorders

    PubMed Central

    Wen, Zhexing; Nguyen, Ha Nam; Guo, Ziyuan; Lalli, Matthew A.; Wang, Xinyuan; Su, Yijing; Kim, Nam-Shik; Yoon, Ki-Jun; Shin, Jaehoon; Zhang, Ce; Makri, Georgia; Nauen, David; Yu, Huimei; Guzman, Elmer; Chiang, Cheng-Hsuan; Yoritomo, Nadine; Kaibuchi, Kozo; Zou, Jizhong; Christian, Kimberly M.; Cheng, Linzhao; Ross, Christopher A.; Margolis, Russell L.; Chen, Gong; Kosik, Kenneth S.; Song, Hongjun; Ming, Guo-li

    2015-01-01

    Dysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders1, and ‘a disease of synapses’ is the major hypothesis for the biological basis of schizophrenia2. Although this hypothesis has gained indirect support from human post-mortem brain analyses2–4 and genetic studies5–10, little is known about the pathophysiology of synapses in patient neurons and how susceptibility genes for mental disorders could lead to synaptic deficits in humans. Genetics of most psychiatric disorders are extremely complex due to multiple susceptibility variants with low penetrance and variable phenotypes11. Rare, multiply affected, large families in which a single genetic locus is probably responsible for conferring susceptibility have proven invaluable for the study of complex disorders. Here we generated induced pluripotent stem (iPS) cells from four members of a family in which a frameshift mutation of disrupted in schizophrenia 1 (DISC1) co-segregated with major psychiatric disorders12 and we further produced different isogenic iPS cell lines via gene editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons. Mutant DISC1 depletes wild-type DISC1 protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons. Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders. PMID:25132547

  10. Craniofacial morphology in children with cystic fibrosis.

    PubMed

    Hellsing, E; Brattström, V; Strandvik, B

    1992-04-01

    Cystic fibrosis (CF) is a hereditary metabolic disorder with clinical symptoms of abnormal mucus production. This blocks the airways, gives pancreatic insufficiency, and increases sweat electrolytes. The progressive respiratory disease often leads to respiratory insufficiency and cor pulmonale. The aim of the present investigation was to examine the facial morphology in children with cystic fibrosis. The sample comprised 11 children with cystic fibrosis, who were divided in two groups, one with gastrointestinal disorders and the other with predominantly respiratory insufficiency. Eleven healthy children with normal occlusions were selected as controls. Lateral skull radiographs obtained in natural head posture were digitized, and linear and angular variables for the different groups calculated and compared statistically. The cystic fibrosis group showed open bite, decreased posterior facial height, increased mandibular and craniocervical inclination. Additionally, within the CF-group, the children with respiratory insufficiency differed more from the controls than the children with gastrointestinal disorders. Despite the small number of subjects, the facial morphology of the CF children showed a similar pattern to that of children with nasal respiratory obstruction due to enlarged adenoids or tonsils.

  11. Human Genetic Disorders Caused by Mutations in Genes Encoding Biosynthetic Enzymes for Sulfated Glycosaminoglycans*

    PubMed Central

    Mizumoto, Shuji; Ikegawa, Shiro; Sugahara, Kazuyuki

    2013-01-01

    A number of genetic disorders are caused by mutations in the genes encoding glycosyltransferases and sulfotransferases, enzymes responsible for the synthesis of sulfated glycosaminoglycan (GAG) side chains of proteoglycans, including chondroitin sulfate, dermatan sulfate, and heparan sulfate. The phenotypes of these genetic disorders reflect disturbances in crucial biological functions of GAGs in human. Recent studies have revealed that mutations in genes encoding chondroitin sulfate and dermatan sulfate biosynthetic enzymes cause various disorders of connective tissues. This minireview focuses on growing glycobiological studies of recently described genetic diseases caused by disturbances in biosynthetic enzymes for sulfated GAGs. PMID:23457301

  12. Craniofacial features of children with spinal deformities

    PubMed Central

    Segatto, Emil; Lippold, Carsten; Végh, András

    2008-01-01

    Background The objective of this epidemiological study is to map the dentofacial anomalies that can be correlated to the two most frequent spinal diseases responsible for postural abnormalities and that can be clinically identified by the orthodontic examination. Methods Twenty-three children with Scheuermann's disease participated in the study (mean age: 14Y8M; SD: 1Y8M), 28 with Scoliosis (mean age: 14Y7M; SD: 2Y3M) and a control group of 68 orthopedically healthy children (mean age: 14Y8M; SD: 0Y11M). Standardized orthodontic screening protocols were used to map the occlusal relations in the sagittal, vertical, and transversal dimensions, space relations of the maxillary and mandibular frontal segment, and the TMJ status and function. The examinations for the children with orthopedic disorders were supplemented by the evaluation of routine orthodontic radiograms – lateral cephalograms and panoramic X-rays. Results The majority of the dentofacial features examined revealed more and greater abnormalities among patients in the Scheuermann's disease group than in the scoliosis group. In the latter group the proportion of the TMJ symptoms and the consecutive functional deviations were greater. When comparing the values of the two spinal-disorder groups and the control group, statistically significant differences (p < .05) occurred for the following measurements: frequency of unilateral Cl.II. molar occlusion, overjet and extreme overjet mean value (Scheuermann's disease group), as well as the frequency of TMJ pathological symptoms (scoliosis group). The evaluation of the panoramic X-rays showed significant differences among the mandibular measurements of the two spinal-disorder groups. Within the framework of the evaluation of the cephalograms significant differences (p < .05) were found only in the case of dental relations. However, several values differed significantly from the Ricketts' norms, none of the indices strictly characterized any of the groups with

  13. Complex posttraumatic stress disorder and survivors of human rights violations.

    PubMed

    McDonnell, Matthew; Robjant, Katy; Katona, Cornelius

    2013-01-01

    This article reviews recent findings on Complex Posttraumatic Stress Disorder (CPTSD) and proposes future research which would help to establish the nature of CPTSD in relation to Posttraumatic Stress Disorder (PTSD). Research on survivors of torture and war has found that CPTSD can occur when there is no history of childhood abuse. fMRI studies appear to highlight differences in neural activity in individuals exhibiting primary dissociation compared with individuals exhibiting secondary dissociation. Research has begun to show that, when symptoms of secondary dissociation are appropriately managed, exposure-based therapies are an effective treatment for individuals with CPTSD. Much research on CPTSD has emphasized its developmental basis and the disruptive effects of trauma in childhood and adolescence on subsequent emotional development. However, some studies on survivors of torture in adult life identify similar symptom patterns, despite there being no history of childhood trauma. It is argued that comparative research is required between victims of developmental trauma (such as childhood sexual abuse) and victims who experienced prolonged interpersonal trauma in adulthood (such as torture), as this could be useful in establishing the cause of CPTSD and in delineating clinically and therapeutically meaningful subtypes. It is also proposed that a focus on underlying neurobiological processes would help in developing and refining CPTSD as a construct and informing treatment.

  14. Microgravity reduces sleep-disordered breathing in humans

    NASA Technical Reports Server (NTRS)

    Elliott, A. R.; Shea, S. A.; Dijk, D. J.; Wyatt, J. K.; Riel, E.; Neri, D. F.; Czeisler, C. A.; West, J. B.; Prisk, G. K.

    2001-01-01

    To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.

  15. Mechanisms of interstrand DNA crosslink repair and human disorders.

    PubMed

    Hashimoto, Satoru; Anai, Hirofumi; Hanada, Katsuhiro

    2016-01-01

    Interstrand DNA crosslinks (ICLs) are the link between Watson-Crick strands of DNAs with the covalent bond and prevent separation of DNA strands. Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple. So far, nucleotide excision repair (NER), structure-specific endonucleases, translesion DNA synthesis (TLS), homologous recombination (HR), and factors responsible for Fanconi anemia (FA) are identified to be involved in ICL repair. Since the presence of ICL lesions causes severe defects in transcription and DNA replication, mutations in these DNA repair pathways give rise to a various hereditary disorders. NER plays an important role for the ICL recognition and removal in quiescent cells, and defects of NER causes congential progeria syndrome, such as xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. On the other hand, the ICL repair in S phase requires more complicated orchestration of multiple factors, including structure-specific endonucleases, and TLS, and HR. Disturbed this ICL repair orchestration in S phase causes genome instability resulting a cancer prone disease, Fanconi anemia. So far more than 30 factors in ICL repair have already identified. Recently, a new factor, UHRF1, was discovered as a sensor of ICLs. In addition to this, numbers of nucleases that are involved in the first incision, also called unhooking, of ICL lesions have also been identified. Here we summarize the recent studies of ICL associated disorders and repair mechanism, with emphasis in the first incision of ICLs.

  16. Insights from human congenital disorders of intestinal lipid metabolism

    PubMed Central

    Levy, Emile

    2015-01-01

    The intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic products from the brush border membrane to the endoplasmic reticulum, lipid esterification, Apo synthesis, and ultimately the packaging of lipid and Apo components into chylomicrons (CMs). Deciphering inherited disorders of intracellular CM elaboration afforded new insight into the key functions of crucial intracellular proteins, such as Apo B, microsomal TG transfer protein, and Sar1b GTPase, the defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and CM retention disease, respectively. These “experiments of nature” are characterized by fat malabsorption, steatorrhea, failure to thrive, low plasma levels of TGs and cholesterol, and deficiency of liposoluble vitamins and essential FAs. After summarizing and discussing the functions and regulation of these proteins for reader’s comprehension, the current review focuses on their specific roles in malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while dissecting the spectrum of clinical manifestations and managements. The influence of newly discovered proteins (proprotein convertase subtilisin/kexin type 9 and angiopoietin-like 3 protein) on fat absorption has also been provided. Finally, it is stressed how the overexpression or polymorphism status of the critical intracellular proteins promotes dyslipidemia and cardiometabolic disorders. PMID:25387865

  17. Human proactive aggression: association with personality disorders and psychopathy.

    PubMed

    Nouvion, Sylvain O; Cherek, Don R; Lane, Scott D; Tcheremissine, Oleg V; Lieving, Lori M

    2007-01-01

    Aggressive behaviors can be divided into two categories: reactive and proactive. Reactive aggressive behaviors occur in response to a stimulus or provocation. Proactive aggressive behaviors occur without provocation and are goal directed. A number of findings have suggested that individuals displaying proactive aggression may be discerned from individuals not displaying proactive aggression on measures of personality, psychopathology and psychopathy as well as in aggressive histories and type and severity of aggressive behaviors committed. In this study, subjects were recruited from a large urban community and classified as proactive (n = 20), reactive-only (n = 20) or nonaggressive (n = 10) based on laboratory behavioral testing. Subjects were administered a battery of questionnaires and structured interviews pertaining to personality disorders and psychopathy. It was hypothesized that proactive aggressive subjects would show greater numbers of personality disorders and have greater psychopathy relative to reactive-only and nonaggressive subjects. These hypotheses were supported. These results suggest that proactive aggression may be identified in a laboratory-based task, and differences between proactive and reactive-only aggressors can be detected. 2007 Wiley-Liss, Inc.

  18. Minireview: human obesity-lessons from monogenic disorders.

    PubMed

    O'Rahilly, Stephen; Farooqi, I Sadaf; Yeo, Giles S H; Challis, Benjamin G

    2003-09-01

    Genetic influences on the determination of human fat mass are profound and powerful, a statement that does not conflict with the obvious influence of environmental factors that drive recent changes in the prevalence of obesity. The assertion of the importance of genetic factors has, until recently, largely been based on twin and adoption studies. However, in the last 6 yr, a number of human genes have been identified in which major missense or nonsense mutations are sufficient in themselves to result in severe early-onset obesity, usually associated with disruption of normal appetite control mechanisms. Progress in the identification of more common, subtler genetic variants that influence fat mass in larger numbers of people has been slower, but discernible. Human genetics will continue to make an invaluable contribution to the study of human obesity by identifying critical molecular components of the human energy balance regulatory systems, pointing the way toward more targeted and effective therapies and assisting the prediction of individual responses to environmental manipulations.

  19. Obstructive sleep apnoea in children with craniofacial syndromes.

    PubMed

    Cielo, Christopher M; Marcus, Carole L

    2015-06-01

    Obstructive sleep apnoea syndrome (OSAS) is common in children. Craniofacial anomalies such as cleft palate are among the most common congenital conditions. Children with a variety of craniofacial conditions, including cleft palate, micrognathia, craniosynostosis, and midface hypoplasia are at increased risk for OSAS. Available evidence, which is largely limited to surgical case series and retrospective studies, suggests that OSAS can be successfully managed in these children through both surgical and non-surgical techniques. Prospective studies using larger cohorts of patients and including polysomnograms are needed to better understand the risk factors for this patient population and the efficacy of treatment options for OSAS and their underlying conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome.

    PubMed

    Ullrich, N J; Silvera, V M; Campbell, S E; Gordon, L B

    2012-09-01

    HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the scope of structural bone and soft-tissue craniofacial abnormalities in HGPS through CT or MR imaging. Using The Progeria Research Foundation Medical and Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age, were comprehensively reviewed. Eight newly identified abnormalities involving the calvaria, skull base, and soft tissues of the face and orbits were present with prevalences between 43% and 100%. These included J-shaped sellas, a mottled appearance and increased vascular markings of the calvaria, abnormally configured mandibular condyles, hypoplastic articular eminences, small zygomatic arches, prominent parotid glands, and optic nerve kinking. This expanded craniofacial characterization helps link disease features and improves our ability to evaluate how underlying genetic and cellular abnormalities culminate in a disease phenotype.

  1. Generation algorithm of craniofacial structure contour in cephalometric images

    NASA Astrophysics Data System (ADS)

    Mondal, Tanmoy; Jain, Ashish; Sardana, H. K.

    2010-02-01

    Anatomical structure tracing on cephalograms is a significant way to obtain cephalometric analysis. Computerized cephalometric analysis involves both manual and automatic approaches. The manual approach is limited in accuracy and repeatability. In this paper we have attempted to develop and test a novel method for automatic localization of craniofacial structure based on the detected edges on the region of interest. According to the grey scale feature at the different region of the cephalometric images, an algorithm for obtaining tissue contour is put forward. Using edge detection with specific threshold an improved bidirectional contour tracing approach is proposed by an interactive selection of the starting edge pixels, the tracking process searches repetitively for an edge pixel at the neighborhood of previously searched edge pixel to segment images, and then craniofacial structures are obtained. The effectiveness of the algorithm is demonstrated by the preliminary experimental results obtained with the proposed method.

  2. Fibrous dysplasia of bone: craniofacial and dental implications.

    PubMed

    Burke, A B; Collins, M T; Boyce, A M

    2016-08-05

    Fibrous dysplasia (FD) is a rare bone disease caused by postzygotic somatic activating mutations in the GNAS gene, which lead to constitutive activation of adenylyl cyclase and elevated levels of cyclic AMP, which act on downstream signaling pathways and cause normal bone to be replaced with fibrous tissue and abnormal (woven) bone. The bone disease may occur in one bone (monostotic), multiple bones (polyostotic), or in combination with hyperfunctioning endocrinopathies and hyperpigmented skin lesions (in the setting of McCune-Albright Syndrome). FD is common in the craniofacial skeleton, causing significant dysmorphic features, bone pain, and dental anomalies. This review summarizes the pathophysiology, clinical findings, and treatment of FD, with an emphasis on the craniofacial and oral manifestations of the disease.

  3. Coordinate systems integration for development of malaysian craniofacial database.

    PubMed

    Rajion, Zainul; Suwardhi, Deni; Setan, Halim; Chong, Albert; Majid, Zulkepli; Ahmad, Anuar; Rani Samsudin, Ab; Aziz, Izhar; Wan Harun, W A R

    2005-01-01

    This study presents a data registration method for craniofacial spatial data of different modalities. The data consists of three dimensional (3D) vector and raster data models. The data is stored in object relational database. The data capture devices are Laser scanner, CT (Computed Tomography) scan and CR (Close Range) Photogrammetry. The objective of the registration is to transform the data from various coordinate systems into a single 3-D Cartesian coordinate system. The standard error of the registration obtained from multimodal imaging devices using 3D affine transformation is in the ranged of 1-2 mm. This study is a step forward for storing the spatial craniofacial data in one reference system in database.

  4. Clinical outcome of 285 Medpor grafts used for craniofacial reconstruction.

    PubMed

    Cenzi, Roberto; Farina, Antonio; Zuccarino, Luca; Carinci, Francesco

    2005-07-01

    Porous polyethylene (Medpor) is an alloplastic material worldwide used for craniofacial reconstruction. To evaluate complications and risk factors associated with this synthetic graft, a retrospective study was performed. A series of 285 Medpor grafts were placed in 187 patients. Age, sex, diagnosis at admission, site, type of surgical insertion, type of fixation, and outcome (no complications, anesthesia, exposure, infection, and implant remodeling and removal) are considered. By means of univariate and multivariate analyses, we detect variables most associated with poor outcome. Univariate analysis showed that graft "survival" curves stratified according to (1) diagnosis at admission and (2) site are statistically significant. Subsequently, a Cox analysis was performed: both variables are also predictors of graft outcome. Porous polyethylene is a reliable alloplastic material that can be satisfactory used for craniofacial reconstruction. However, some sites (i.e., nose, maxilla, and ear) and diagnosis at admission (i.e., syndromic patients previously operated) are related to an higher risk of implant failure.

  5. Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions.

    PubMed

    Izumi, Aiko; Iijima, Yoshimi; Noguchi, Hiroko; Numakawa, Tadahiro; Okada, Takeya; Hori, Hiroaki; Kato, Tadafumi; Tatsumi, Masahiko; Kosuga, Asako; Kamijima, Kunitoshi; Asada, Takashi; Arima, Kunimasa; Saitoh, Osamu; Shiosaka, Sadao; Kunugi, Hiroshi

    2008-12-01

    Human neuropsin (NP) (hNP) has been implicated in the progressive change of cognitive abilities during primate evolution. The hNP gene maps to chromosome 19q13, a region reportedly linked to schizophrenia and bipolar disorder. Therefore, hNP is a functional and positional candidate gene for association with schizophrenia, mood disorders, and cognitive ability. Polymorphism screening was performed for the entire hNP gene. The core promoter region was determined and whether or not transcriptional activity alters in an allele-dependent manner was examined by using the dual-luciferase system. Allelic and genotypic distributions of five single-nucleotide polymorphisms (SNPs) were compared between patients with schizophrenia (n=439), major depression (n=409), bipolar disorder (n=207), and controls (n=727). A possible association of the hNP genotype with memory index (assessed with Wechsler Memory Scale, revised, WMS-R) and intelligence quotient (IQ assessed with Wechsler Adult Intelligence Scale, revised; WAIS-R) was examined in healthy controls (n=166). A total of 28 SNPs, including nine novel SNPs, were identified. No significant effects on transcriptional activity were observed for SNPs in the promoter region. A significant allelic association was found between several SNPs and bipolar disorder (for SNP23 at the 3' regulatory region; odds ratio 1.48, 95% confidential interval 1.16-1.88, P=0.0015). However, such an association was not detected for schizophrenia or depression. Significant differences were observed between SNP23 and attention/concentration sub-scale score of WMS-R (P=0.016) and verbal IQ (P<0.001). Genetic variation of the hNP gene may contribute to molecular mechanisms of bipolar disorder and some aspects of memory and intelligence.

  6. Multimodality imaging for precise localization of craniofacial osteomyelitis.

    PubMed

    Strumas, Nick; Antonyshyn, Oleh; Caldwell, Curtis B; Mainprize, James

    2003-03-01

    Functional imaging identifies areas of abnormal bone turnover, providing a useful adjunct in the treatment of osteomyelitis and bone tumors. The low resolution and lack of anatomical detail limit the application of bone scans in craniofacial surgery, however. Multimodality image registration addresses this problem by fusing functional images (single photon emission computed tomography [SPECT]) to high-resolution structural images (computed tomography [CT]) for precise anatomical delineation of bone activity. This article describes a technique for spatial registration of CT and SPECT images to provide precise anatomical delineation of abnormal bone turnover, thereby guiding the extent of resection in the management of craniofacial osteomyelitis. Standard CT and SPECT imaging protocols were used in imaging the skull from the vertex to the mentum. Image data were imported into Analyze (Biomedical Imaging Resource; Mayo Foundation, Rochester, MN) on a dedicated Windows NT (Microsoft Corporation, Redmond, WA) workstation. Using the CT data, the craniofacial skeleton, osteotomy segments, and bone grafts were interactively mapped out. Consecutive axial slices were then reconstructed to form a three-dimensional volume of interest. The CT-derived volume of interest was registered to the technetium Tc 99m-methylene diphosphonate SPECT scan using the Analyze program to provide a fused multimodality image. The imaging technique was used to localize osteomyelitis in a complex craniofacial reconstruction. The fused images guided the extent of resection during surgery, and postoperative microbiological and histological testing confirmed the diagnosis. Multimodality image registration provides a readily available method to relate facial skeletal anatomy and physiology. This technique is valuable in planning and monitoring therapeutic interventions in clinical conditions in which bone turnover is abnormal.

  7. Cephalometric craniofacial characteristics in patients with temporomandibular joint ankylosis.

    PubMed

    Ko, Ellen Wen-Ching; Huang, Chiung-Shing; Chen, Yu-Ray; Figueroa, Alvaro A

    2005-07-01

    The sequelae of temporomanibular joint (TMJ) ankylosis include limitation of jaw movement, interference of oral function and affects on the craniofacial growth. Analysis of the craniofacial form of TMJ ankylosis offers guidelines for managing this disease. Forty-five patients with intraarticular TMJ ankylosis were collected from the files at the Chang Gung Craniofacial Center. There were 21 male and 24 female patients, aged 3 to 47 years. Thirty-seven patients were unilaterally affected and eight had bilateral involvement. Patients were grouped according to gender and age. Both the medical history and onset of the disease were investigated in all patients. The pretreatment lateral cephalograms were used for analysis. The variables were compared with the Chinese norms with corresponding sex and age groups. The etiology included 48.9% facial trauma history, 17.8% traumatic delivery or birth injury, 15.6% middle ear or dental infection, 2.2% chronic arthritis and 15.6% unknown causes. The onset of mouth opening limitation was under 16 years of age. The average total mandibular length was less than the norm by 30 mm. Each patient presented with a mandible that had backward rotation with chin recession. Accentuated antegonial notch and inferiorly located condyle were observed on the affected side. The maxilla was shorter and the ANB was larger than the norm by 10 degrees but the overbite and overjet were within normal ranges. The facial growth was severely disturbed in terms of dimension, morphology and direction of growth in patients with TMJ ankylosis. Better management of mandibular fractures, good infection control and early treatment intervention are ways to reduce the influence on craniofacial growth.

  8. Sagittal back contour and craniofacial morphology in preadolescents.

    PubMed

    Lippold, Carsten; Segatto, Emil; Végh, András; Drerup, Burkhard; Moiseenko, Tatjana; Danesh, Gholamreza

    2010-03-01

    The aim of this study was to analyze the correlation ratios between the sagittal back contour (flèche cervicale and lombaire, trunk inclination) and selected parameters of craniofacial morphology in children. The patient sample consisted of 66 healthy children with a mean age of 11.2 years (SD 1.6 years), of which 34 were male (mean age 11.5 years, SD 1.3 years) and 32 were females (mean age 10.9 years, SD 1.9 years). The children were recruited during the preparation of the initial orthodontic treatment records. Craniofacial morphology was analyzed by six angular measurements: facial axis, mandibular plane angle, inner gonial angle, lower facial height, facial depth and maxilla position. Rasterstereography was used for reconstruction of the spinal back sagittal profile. From the profile flèche cervicale, flèche lombaire and trunk inclination were determined and the correlations with the craniofacial morphology were calculated (Pearson and Mann-Whitney U test). Significant correlations were found with respect to the inner gonial angle and the flèche cervicale, the mandibular plane angle and the flèche lombaire, the inner gonial angle and the flèche lombaire, and the angular lower facial height and the flèche lombaire, as well as the inner gonial angle and the trunk inclination. The craniofacial vertical growth pattern, presented by mandibular plane angle, inner gonial angle and the angular lower facial height, and the correlation to flèche cervicale and lombaire as well as trunk inclination reveal correlations between growth pattern and sagittal back contour.

  9. Sagittal back contour and craniofacial morphology in preadolescents

    PubMed Central

    Lippold, Carsten; Végh, András; Drerup, Burkhard; Moiseenko, Tatjana; Danesh, Gholamreza

    2009-01-01

    The aim of this study was to analyze the correlation ratios between the sagittal back contour (flèche cervicale and lombaire, trunk inclination) and selected parameters of craniofacial morphology in children. The patient sample consisted of 66 healthy children with a mean age of 11.2 years (SD 1.6 years), of which 34 were male (mean age 11.5 years, SD 1.3 years) and 32 were females (mean age 10.9 years, SD 1.9 years). The children were recruited during the preparation of the initial orthodontic treatment records. Craniofacial morphology was analyzed by six angular measurements: facial axis, mandibular plane angle, inner gonial angle, lower facial height, facial depth and maxilla position. Rasterstereography was used for reconstruction of the spinal back sagittal profile. From the profile flèche cervicale, flèche lombaire and trunk inclination were determined and the correlations with the craniofacial morphology were calculated (Pearson and Mann–Whitney U test). Significant correlations were found with respect to the inner gonial angle and the flèche cervicale, the mandibular plane angle and the flèche lombaire, the inner gonial angle and the flèche lombaire, and the angular lower facial height and the flèche lombaire, as well as the inner gonial angle and the trunk inclination. The craniofacial vertical growth pattern, presented by mandibular plane angle, inner gonial angle and the angular lower facial height, and the correlation to flèche cervicale and lombaire as well as trunk inclination reveal correlations between growth pattern and sagittal back contour. PMID:19946733

  10. Craniofacial Deviations in the Children With Nasal Obstruction.

    PubMed

    Ant, Ayca; Kemaloglu, Yusuf Kemal; Yilmaz, Metin; Dilci, Alper

    2017-01-20

    Nasal obstruction mainly caused by adenoid hypertrophy in children affects the craniofacial growth and development process, and the craniofacial deviations and/or differences reported in the children are very similar to those in the adults with obstructive sleep apnea syndrome (OSAS). The authors aimed to look for relationships of the linear craniofacial dimensions in the children suffering from nasal obstruction with age, degree of clinical nasal obstruction score (CNOS), and relative size of the adenoid mass within the nasopharynx in their study.Fifty-five children suffering from nasal obstruction were retrospectively enrolled, and clinical data was used to calculate CNOS. On the lateral cephalometric radiographies, 9 linear variables were measured and adenoidal-nasopharyngeal ratio (ANR) was calculated.The data presented that, not CNOS, but ANR shown decrease by age, while many skeletal variables with exception of the nasopharyngeal and adenoidal postero-anterior dimensions were increased by age. Further, it was found that while CNOS were negatively correlated with the anterior cranial base length, anterior-superior facial height, and maxillary depth, ANR disclosed significant correlation only with the anteriorsuperior facial height. The authors' results support that nasal obstruction in the children was related not only to the adenoidal hypertrophy. Although relative size of the adenoidal mass in relation to the nasopharynx decreased by age, nasal obstruction was still present. Further, these results support that craniofacial deviations and/or differences in the children with nasal obstruction is similar to the adult OSAS patients. Smaller dimensions related to the naso-maxillary complex in the children with more severe nasal obstruction appear to be continuous by age. Hence, it could be said that narrow naso-maxillary complex could contribute to proceed nasal obstruction by age, which may contribute to OSAS in the adults.

  11. Female adolescent craniofacial growth spurts: real or fiction?

    PubMed

    Buschang, Peter H; Jacob, Helder B; Demirjian, Arto

    2013-12-01

    The purpose of the study is to determine whether the various aspects of the craniofacial complex exhibit female adolescent growth spurts. Multilevel polynomial models were used to estimate the growth curves of a mixed-longitudinal sample of 111 untreated females 10-15 years of age. To evaluate the horizontal and vertical movements of the individual landmarks relative to stable structures, the tracings were superimposed on the natural reference structures in the anterior cranial base. The horizontal and vertical growth changes of four landmarks and the changes of three traditional linear measurements were evaluated. Posterior nasal spine (PNS) moved posteriorly at a constant rate of approximately 0.12mm/year. Five measures showed changes in growth velocity (i.e. quadratic growth curves) but not adolescent growth spurts, including the anterior movements of anterior nasal spine (ANS) and pogonion (Pg), the inferior movements of gonion (Go), and the increases in ANS-PNS and condylion to pogonion (Co-Pg). Five measurements, including the inferior movements of ANS, PNS and Pg, the posterior movements of Go, and the increases of Go-Pg exhibited adolescent growth spurts. Peak growth velocities were attained between 11.4 and 12.8 years of age, approximately 0.7-1.4 years earlier in the maxilla than mandible. While the vertical aspects of craniofacial growth exhibit distinct female adolescent growth spurts, with peak rates occurring earlier in the maxilla than mandible, most horizontal aspects of craniofacial growth do not exhibit an adolescent spurt.

  12. Web-based cephalometric procedure for craniofacial and dentition analyses

    NASA Astrophysics Data System (ADS)

    Arun Kumar, N. S.; Kamath, Srijit R.; Ram, S.; Muthukumaran, B.; Venkatachalapathy, A.; Nandakumar, A.; Jayakumar, P.

    2000-05-01

    Craniofacial analysis is a very important and widely used procedure in orthodontic caphalometry, which plays a key role in diagnosis and treatment planning. This involves establishing reference standards and specification of landmarks and variables. The manual approach takes up a tremendous amount of the orthodontist's time. In this paper, we developed a web-based approach for the craniofacial and dentition analyses. A digital computed radiography (CR) system is utilized for obtaining the craniofacial image, which is stored as a bitmap file. The system comprises of two components - a server and a client. The server component is a program that runs on a remote machine. To use the system, the user has to connect to the website. The client component is now activated, which uploads the image from the PC and displays it on the canvas area. The landmarks are identified using a mouse interface. The reference lines are generated. The resulting image is then sent to the server which performs all measurement and calculates the mean, standard deviation, etc. of the variables. The results generated are sent immediately to the client where it is displayed on a separate frame along with the standard values for comparison. This system eliminates the need for every user to load other expensive programs on his machine.

  13. Penetrating craniofacial injuries in children with wooden and metal chopsticks.

    PubMed

    Park, Se-Hyuck; Cho, Ki Hong; Shin, Yong Sam; Kim, Se Hyuck; Ahn, Young Hwan; Cho, Kyung Gi; Yoon, Soo Han

    2006-01-01

    Penetrating craniofacial injuries with chopsticks in children are peculiar accidents in the Oriental culture. All 10 cases previously reported were caused by wooden chopsticks that required surgical operations. However, there are no reported injuries with metal chopsticks in the past literature which should have been as common as that of wooden chopstick injuries in Asia. We evaluated the difference of injury patterns and clinical observations between wooden and metal chopstick injuries. We reviewed 6 treated children with penetrating craniofacial injuries from chopsticks: one wooden and five metal chopsticks. One child who had penetration through the nasal cavity presented with temporary rhinorrhea, another with mild hemiparesis, and one child with temporary upward gaze limitation of the left eye. Radiological examination revealed 1 patient with epidural hemorrhage, 1 patient with minimal subdural hemorrhage, and 4 with intracerebral hemorrhage that were fortunately too small to receive surgery. We performed surgical procedure only for a child who had a wooden chopstick that had impacted into the temporal cortex. We followed up all 6 children for more than 1 year, and found that all had fully recovered to near-normal neurological status. We observed that penetrating craniofacial injuries with metal chopsticks rarely require surgical intervention and usually results in good outcome because the resultant wound is usually small without broken fragments compared to injuries with wooden chopsticks. Copyright 2006 S. Karger AG, Basel

  14. Craniofacial sexual dimorphism patterns and allometry among extant hominids.

    PubMed

    Schaefer, Katrin; Mitteroecker, Philipp; Gunz, Philipp; Bernhard, Markus; Bookstein, Fred L

    2004-12-01

    Craniofacial sexual dimorphism in primates varies in both magnitude and pattern among species. In the past two decades, there has been an increasing emphasis in exploring the correlations of these patterns with taxonomy and the variation in patterns within and among the craniofacial regions. Scrutinising these relationships for hominids, we decompose the craniofacial morphology in five taxa: Homo sapiens, Pan paniscus, Pan troglodytes, Gorilla gorilla and Pongo pygmaeus. 3D coordinates of 35 traditional landmarks and 61 semilandmarks, covering five ridge curves, are measured for each of 268 adult and sub-adult specimens and analysed using geometric morphometric methods. A multivariate analysis in size-shape space shows that ontogenetic scaling contributes to the development of sexual dimorphism in all five taxa, but to a varying extent. In absolute as well as in relative terms P. pygmaeus shows the greatest allometric component, followed by G. gorilla. Homo is intermediate, while in Pan the non-allometric constituent part contributes a large fraction to the actual sexual dimorphism, most markedly in the pygmy chimpanzee. An eigendecomposition of the five vectors of sexual dimorphism reveals two dimensions independent of allometry. One separates orang-utan sexual dimorphism from the African apes and Homo, and the other differentiates between the great apes and Homo with Pan mediating. We discuss these patterns and speculate on their use as characters for taxonomic analysis in the fossil record.

  15. Study on the performance of different craniofacial superimposition approaches (I).

    PubMed

    Ibáñez, O; Vicente, R; Navega, D S; Wilkinson, C; Jayaprakash, P T; Huete, M I; Briers, T; Hardiman, R; Navarro, F; Ruiz, E; Cavalli, F; Imaizumi, K; Jankauskas, R; Veselovskaya, E; Abramov, A; Lestón, P; Molinero, F; Cardoso, J; Çağdır, A S; Humpire, D; Nakanishi, Y; Zeuner, A; Ross, A H; Gaudio, D; Damas, S

    2015-12-01

    As part of the scientific tasks coordinated throughout The 'New Methodologies and Protocols of Forensic Identification by Craniofacial Superimposition (MEPROCS)' project, the current study aims to analyse the performance of a diverse set of CFS methodologies and the corresponding technical approaches when dealing with a common dataset of real-world cases. Thus, a multiple-lab study on craniofacial superimposition has been carried out for the first time. In particular, 26 participants from 17 different institutions in 13 countries were asked to deal with 14 identification scenarios, some of them involving the comparison of multiple candidates and unknown skulls. In total, 60 craniofacial superimposition problems divided in two set of females and males. Each participant follow her/his own methodology and employed her/his particular technological means. For each single case they were asked to report the final identification decision (either positive or negative) along with the rationale supporting the decision and at least one image illustrating the overlay/superimposition outcome. This study is expected to provide important insights to better understand the most convenient characteristics of every method included in this study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Endoscopic delivery of calcium phosphate cement for secondary craniofacial reconstruction.

    PubMed

    Francis, Cameron S; Wong, Ryan K; Cohen, Steven R

    2012-11-01

    Contour defects are common following primary craniofacial procedures including cranial vault remodeling, fronto-orbital and midface advancements, and complex posttraumatic reconstructions. When onlayed as fast-setting pastes, calcium phosphate cements (CPCs) have been used to effectively correct contour defects in open secondary reconstruction procedures. Here, we describe an endoscopic procedure using an injectable CPC and compare surgical outcomes with the open technique. A retrospective review was conducted for 36 consecutive patients aged 3.0-28.9 years (mean, 10.1 years) who underwent secondary craniofacial reconstruction over a 3-year period. Patients were stratified into endoscopic or open groups depending on the surgical approach utilized. Mean operative time was significantly shorter (P < 0.001) for the endoscopic group (64 minutes) than for the open group (131 minutes). Similarly, hospital stay was significantly shorter (P = 0.005) in the endoscopic group than in the open group. There was also a significant difference with respect to cost (P < 0.001), with the endoscopic approach resulting in a per-patient cost savings of $2208.05. In conclusion, endoscopic delivery of CPC appears to be a safe, efficacious, and cost-effective method of performing secondary craniofacial reconstruction, with the additional benefits of decreased operative time and shorter postoperative hospital stay when compared with an open procedure.

  17. Differential protein import deficiencies in human peroxisome assembly disorders

    PubMed Central

    1994-01-01

    Two peroxisome targeting signals (PTSs) for matrix proteins have been well defined to date. PTS1 comprises a COOH-terminal tripeptide, SKL, and has been found in several matrix proteins, whereas PTS2 has been found only in peroxisomal thiolase and is contained within an NH2- terminal cleavable presequence. We have investigated the functional integrity of the import routes for PTS1 and PTS2 in fibroblasts from patients suffering from peroxisome assembly disorders. Three of the five complementation groups tested showed a general loss of PTS1 and PTS2 import. Two complementation groups showed a differential loss of peroxisomal protein import: group I cells were able to import a PTS1- but not a PTS2- containing reporter protein into their peroxisomes, and group IV cells were able to import the PTS2 but not the PTS1 reporter into aberrant, peroxisomal ghostlike structures. The observation that the PTS2 import pathway is intact only in group IV cells is supported by the protection of endogenous thiolase from protease degradation in group IV cells and its sensitivity in the remaining complementation groups, including the partialized disorder of group I. The functionality of the PTS2 import pathway and colocalization of endogenous thiolase with the peroxisomal membranes in group IV cells was substantiated further using immunofluorescence, subcellular fractionation, and immunoelectron microscopy. The phenotypes of group I and IV cells provide the first evidence for differential import deficiencies in higher eukaryotes. These phenotypes are analogous to those found in Saccharomyces cerevisiae peroxisome assembly mutants. PMID:7910611

  18. 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.

  19. Effect of prenatal alcohol exposure on bony craniofacial development: a mouse MicroCT study.

    PubMed

    Shen, Li; Ai, Huisi; Liang, Yun; Ren, Xiaowei; Anthony, Charles Bruce; Goodlett, Charles R; Ward, Richard; Zhou, Feng C

    2013-08-01

    Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI® liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC < CHOW and ALC < PF. While covarying for gender and head size or circumference, the treatment affected the total skull and mandible at P7 (ALC > CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC = 0.967), between ALC and PF (AUC = 0.995), and between PF and CHOW (AUC = 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper

  20. Injection of adjuvant but not acidic saline into craniofacial muscle evokes nociceptive behaviors and neuropeptide expression.

    PubMed

    Ambalavanar, R; Yallampalli, C; Yallampalli, U; Dessem, D

    2007-11-09

    Craniofacial muscle pain including muscular temporomandibular disorders accounts for a substantial portion of all pain perceived in the head and neck region. In spite of its high clinical prevalence, the mechanisms of chronic craniofacial muscle pain are not well understood. Injection of acidic saline into rodent hindlimb muscles produces pathologies which resemble muscular pathologies in chronic pain patients. Here we investigated whether analogous transformations occur following repeated injections of acidic saline into the rat masseter muscle. Injection of acidic saline (pH 4) into the masseter muscle transiently lowered i.m. pH to levels comparable to those reported for rodent hindlimb muscles. Nevertheless, repeated unilateral or bilateral injections of acidic saline (pH 4) into the masseter muscle failed to alter nociceptive behavioral responses as occurs in the hindlimb. Changing the pH of injected saline to pH 3.0 or 5.0 also did not evoke nocifensive behavior. Acid sensing ion channel 3 receptors, which are implicated in transformations following acidification of hindlimb muscles, were found on trigeminal ganglion muscle afferent neurons via combined neuronal tracing and immunocytochemistry. In contrast to the acidic saline, injection of complete Freund's adjuvant (CFA) into the masseter muscle induced mechanical allodynia for 3 weeks, thermal hyperalgesia for 1 week and an increase in the number of calcitonin gene-related peptide (CGRP)-immunoreactive muscle afferent neurons in the trigeminal ganglion. Although pH may alter CGRP release in primary afferent neurons, the number of CGRP-muscle afferent neurons did not change following i.m. injection of acidic saline. Further, there was no change in ganglionic iCGRP levels at 1, 4 or 12 days after i.m. injection of acidic saline. While these findings extend our earlier reports that CFA-induced muscle inflammation results in behavioral and neuropeptide changes they further suggest that i.m. acidification in

  1. Mouse models of food allergy: how well do they simulate the human disorder?

    PubMed

    Gonipeta, Babu; Kim, Eunjung; Gangur, Venu

    2015-01-01

    Food allergy is a growing health problem with serious concerns due to high potential for fatality. Rapid advances in the knowledge on causes and mechanisms as well as in developing effective prevention/therapeutic strategies are needed. To meet these goals, mouse models that simulate the human disorder are highly desirable. During the past decade, several mouse models of food allergies have been reported. Here, we briefly reviewed the human disorder and then critically evaluated these models seeking answers to the following important questions: To what extent do they simulate the human disorder? What are the strengths and limitations of these models? What are the challenges facing this scientific area? Our analysis suggest that: (i) the mouse models, with inherent strengths and limitations, are available for many major food allergies; there is scope for additional model development and validation; (ii) models mostly simulate the severe forms of human disorder with similar immune and clinical features; (iii) the approaches used to develop some of the mouse models may be questionable; and (iv) the specific mechanisms of sensitization as wells as oral elicitation of fatal reactions in both humans and mice remains incompletely understood and therefore warrants further research.

  2. 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

  3. 78 FR 39740 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... applications. Place: National Institutes of Health, One Democracy Plaza, 6701 Democracy Boulevard, Bethesda, MD..., Scientific Review Branch, National Institute of Dental and Craniofacial Research, 6701 Democracy Blvd., Rm...

  4. Exploring the Underlying Genetics of Craniofacial Morphology through Various Sources of Knowledge

    PubMed Central

    Roosenboom, Jasmien; Hens, Greet; Mattern, Brooke C.; Shriver, Mark D.

    2016-01-01

    The craniofacial complex is the billboard of sorts containing information about sex, health, ancestry, kinship, genes, and environment. A thorough knowledge of the genes underlying craniofacial morphology is fundamental to understanding craniofacial biology and evolution. These genes can also provide an important foundation for practical efforts like predicting faces from DNA and phenotype-based facial diagnostics. In this work, we focus on the various sources of knowledge regarding the genes that affect patterns of craniofacial development. Although tremendous successes recently have been made using these sources in both methodology and biology, many challenges remain. Primary among these are precise phenotyping techniques and efficient modeling methods. PMID:28053980

  5. Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders

    PubMed Central

    O’Driscoll, Mark

    2008-01-01

    Genomic disorders are a clinically diverse group of conditions caused by gain, loss or re-orientation of a genomic region containing dosage-sensitive genes. One class of genomic disorder is caused by hemizygous deletions resulting in haploinsufficiency of a single or, more usually, several genes. For example, the heterozygous contiguous gene deletion on chromosome 22q11.2 causing DiGeorge syndrome involves at least 20-30 genes. Determining how the copy number variation (CNV) affects human variation and contributes to the aetiology and progression of various genomic disorders represents important questions for the future. Here, I will discuss the functional significance of one form of CNV, haploinsufficiency (i.e. loss of a gene copy), of DNA damage response components and its association with certain genomic disorders. There is increasing evidence that haploinsufficiency for certain genes encoding key players in the cells response to DNA damage, particularly those of the Ataxia Telangiectasia and Rad3-related (ATR)-pathway, has a functional impact. I will review this evidence and present examples of some well known clinically similar genomic disorders that have recently been shown to be defective in the ATR-dependent DNA damage response. Finally, I will discuss the potential implications of a haploinsufficiency-induced defective DNA damage response for the clinical management of certain human genomic disorders. PMID:19440510

  6. The role of genomic imprinting in human developmental disorders: lessons from Prader-Willi syndrome.

    PubMed

    Hanel, M L; Wevrick, R

    2001-03-01

    Normal human development involves a delicate interplay of gene expression in specific tissues at narrow windows of time. Temporally and spatially regulated gene expression is controlled both by gene-specific factors and chromatin-specific factors. Genomic imprinting is the expression of specific genes primarily from only one allele at particular times during development, and is one mechanism implicated in the intricate control of gene expression. Two human genetic disorders, Prader-Willi syndrome (PWS, MIM 176270) and Angelman syndrome (AS, MIM 105830), result from rearrangements of chromosome 15q11-q13, an imprinted region of the human genome. Despite their rarity, disorders such as PWS and AS can give focused insight into the role of genomic imprinting and imprinted genes in human development.

  7. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

    PubMed

    Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

    2012-10-01

    We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery.

  8. Transduction of human recombinant proteins into mitochondria as a protein therapeutic approach for mitochondrial disorders.

    PubMed

    Papadopoulou, Lefkothea C; Tsiftsoglou, Asterios S

    2011-11-01

    Protein therapy is considered an alternative approach to gene therapy for treatment of genetic-metabolic disorders. Human protein therapeutics (PTs), developed via recombinant DNA technology and used for the treatment of these illnesses, act upon membrane-bound receptors to achieve their pharmacological response. On the contrary, proteins that normally act inside the cells cannot be developed as PTs in the conventional way, since they are not able to "cross" the plasma membrane. Furthermore, in mitochondrial disorders, attributed either to depleted or malfunctioned mitochondrial proteins, PTs should also have to reach the subcellular mitochondria to exert their therapeutic potential. Nowadays, there is no effective therapy for mitochondrial disorders. The development of PTs, however, via the Protein Transduction Domain (PTD) technology offered new opportunities for the deliberate delivery of human recombinant proteins inside eukaryotic subcellular organelles. To this end, mitochondrial disorders could be clinically encountered with the delivery of human mitochondrial proteins (engineered via recombinant DNA and PTD technologies) at specific intramitochondrial sites to exert their function. Overall, PTD-mediated Protein Replacement Therapy emerges as a suitable model system for the therapeutic approach for mitochondrial disorders.

  9. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network.

    PubMed

    Podder, Avijit; Latha, N

    2017-06-01

    Intercommunication of Dopamine Receptors (DRs) with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled "Human Dopamine Receptors Interaction Network (DRIN): a systems biology perspective on topology, stability and functionality of the network" (Podder et al., 2014) [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  10. A One-Session Human Immunodeficiency Virus Risk-Reduction Intervention in Adolescents with Psychiatric and Substance Use Disorders

    ERIC Educational Resources Information Center

    Thurstone, Christian; Riggs, Paula D.; Klein, Constance; Mikulich-Gilbertson, Susan K.

    2007-01-01

    Objective: To explore change in human immunodeficiency virus (HIV) risk among teens in outpatient treatment for substance use disorders (SUDs). Method: From December 2002 to August 2004, 50 adolescents (13-19 years) with major depressive disorder, conduct disorder, and one or more non-nicotine SUD completed the Teen Health Survey (THS) at the…

  11. A One-Session Human Immunodeficiency Virus Risk-Reduction Intervention in Adolescents with Psychiatric and Substance Use Disorders

    ERIC Educational Resources Information Center

    Thurstone, Christian; Riggs, Paula D.; Klein, Constance; Mikulich-Gilbertson, Susan K.

    2007-01-01

    Objective: To explore change in human immunodeficiency virus (HIV) risk among teens in outpatient treatment for substance use disorders (SUDs). Method: From December 2002 to August 2004, 50 adolescents (13-19 years) with major depressive disorder, conduct disorder, and one or more non-nicotine SUD completed the Teen Health Survey (THS) at the…

  12. McCune–Albright syndrome with craniofacial dysplasia: Clinical review and surgical management

    PubMed Central

    Belsuzarri, Telmo Augusto Barba; Araujo, João Flavio Mattos; Melro, Carlos Alberto Morassi; Neves, Maick Willen Fernandes; Navarro, Juliano Nery; Brito, Leandro Gomes; Pontelli, Luis Otavio Carneiro; de Abreu Mattos, Luis Gustavo; Gonçales, Tiago Fernandes; Zeviani, Wolnei Marques

    2016-01-01

    Background: Fibrous dysplasia (FD) is a benign fibro-osseous lesion related to an abnormal bone development and replacement by fibrous tissue. FD has three clinical patterns namely monostotic, polyostotic, and the McCune–Albright syndrome (MAS). MAS is a rare genetic disorder (about 3% of all FD's) that comprises a triad of polyostotic FD, café-au-lait skin macules, and precocious puberty. MAS can involve the orbit region and cause stenosis in the optic canal, leading the patient to a progressive visual loss. Methods: We reported a case of craniofacial FD in MAS in a 9-year-old male with progressive visual loss, submitted to optic nerve decompression by fronto-orbito-zygomatic approach, with total recovery. A research was made at Bireme, PubMed, Cochrane, LILACS, and MEDLINE with the keywords: FD/craniofacial/McCune–Albright/Optic compression for the clinical review. Results: A clinical review of the disease was made, the multiple, clinical, and surgical management options were presented, and the case report was reported. Conclusion: MAS is a rare disease with a progressive polyostotic FD. Whenever it affects the orbit region, the optic canal, and it is associated with a progressive visual loss, the urgent optic nerve decompression is mandatory, either manually or with a rapid drill. It is known that aggressive approach is associated with less recurrence; it is also associated with worsening of the visual loss in optic nerve decompression. In MAS cases, multiple and less aggressive surgeries seem to be more suitable. PMID:27057395

  13. Membrane-associated immunoglobulins of human lymphocytes in immunologic disorders

    PubMed Central

    Nicod, Isabelle; Girard, J. P.; Cruchaud, A.

    1973-01-01

    Membrane-associated immunoglobulins of peripheral blood lymphocytes were studied by indirect immunofluorescence for γ, α, μ, κ and λ chains in healthy subjects and patients with immunologic disease. In healthy subjects, heavy chains were found on 30·7% of lymphocytes (γ 15·3%, α 7·2% and μ 8·2%) and light chains on 32·8% of cells (κ 20·4% and λ 12·4%). Patients with humoral immune deficiencies had fewer immunoglobulin-bearing cells; sarcoidosis or thymectomy patients had normal or decreased immunoglobulin-bearing lymphocytes; cells with light chains were fewer than those with heavy chains on their lymphocytes. In some cases, normal levels of serum immunoglobulins were found in the absence of the corresponding immunoglobulin-bearing cells, and in others normal immunoglobulin-bearing lymphocytes were present in the absence of the corresponding serum immunoglobulins. These data suggest that (1) immunoglobulin-bearing lymphocytes in blood do not reflect the condition of immunoglobulin-synthesizing cells in peripheral lymphoid tissues, and (2) in certain immunologic disorders, either some B-lymphocytes do not synthesize immunoglobulins, or immunoglobulins are in such a situation that the whole molecule or part of the molecule is not visualized by current methods. PMID:4587505

  14. Widespread Macromolecular Interaction Perturbations in Human Genetic Disorders

    PubMed Central

    Sahni, Nidhi; Yi, Song; Taipale, Mikko; Fuxman Bass, Juan I.; Coulombe-Huntington, Jasmin; Yang, Fan; Peng, Jian; Weile, Jochen; Karras, Georgios I.; Wang, Yang; Kovács, István A.; Kamburov, Atanas; Krykbaeva, Irina; Lam, Mandy H.; Tucker, George; Khurana, Vikram; Sharma, Amitabh; Liu, Yang-Yu; Yachie, Nozomu; Zhong, Quan; Shen, Yun; Palagi, Alexandre; San-Miguel, Adriana; Fan, Changyu; Balcha, Dawit; Dricot, Amelie; Jordan, Daniel M.; Walsh, Jennifer M.; Shah, Akash A.; Yang, Xinping; Stoyanova, Ani; Leighton, Alex; Calderwood, Michael A.; Jacob, Yves; Cusick, Michael E.; Salehi-Ashtiani, Kourosh; Whitesell, Luke J.; Sunyaev, Shamil; Berger, Bonnie; Barabási, Albert-László; Charloteaux, Benoit; Hill, David E.; Hao, Tong; Roth, Frederick P.; Xia, Yu; Walhout, Albertha J.M.; Lindquist, Susan; Vidal, Marc

    2015-01-01

    SUMMARY How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays. The majority of disease-associated alleles exhibit wild-type chaperone binding profiles, suggesting they preserve protein folding or stability. While common variants from healthy individuals rarely affect interactions, two-thirds of disease-associated alleles perturb protein-protein interactions, with half corresponding to “edgetic” alleles affecting only a subset of interactions while leaving most other interactions unperturbed. With transcription factors, many alleles that leave protein-protein interactions intact affect DNA binding. Different mutations in the same gene leading to different interaction profiles often result in distinct disease phenotypes. Thus disease-associated alleles that perturb distinct protein activities rather than grossly affecting folding and stability are relatively widespread. PMID:25910212

  15. The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

    PubMed Central

    Babu, M. Madan

    2016-01-01

    In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence–structure–function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles by which regulatory mechanisms, such as alternative splicing and asymmetric localization of transcripts that encode disordered regions, can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution. PMID:27911701

  16. Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans

    PubMed Central

    Docherty, Louise E.; Rezwan, Faisal I.; Poole, Rebecca L.; Turner, Claire L. S.; Kivuva, Emma; Maher, Eamonn R.; Smithson, Sarah F.; Hamilton-Shield, Julian P.; Patalan, Michal; Gizewska, Maria; Peregud-Pogorzelski, Jaroslaw; Beygo, Jasmin; Buiting, Karin; Horsthemke, Bernhard; Soellner, Lukas; Begemann, Matthias; Eggermann, Thomas; Baple, Emma; Mansour, Sahar; Temple, I. Karen; Mackay, Deborah J. G.

    2015-01-01

    Human-imprinting disorders are congenital disorders of growth, development and metabolism, associated with disturbance of parent of origin-specific DNA methylation at imprinted loci across the genome. Some imprinting disorders have higher than expected prevalence of monozygotic twinning, of assisted reproductive technology among parents, and of disturbance of multiple imprinted loci, for which few causative trans-acting mutations have been found. Here we report mutations in NLRP5 in five mothers of individuals affected by multilocus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, NLRP7 and NLRP2, cause familial biparental hydatidiform mole and multilocus imprinting disturbance, respectively. Offspring of mothers with NLRP5 mutations have heterogenous clinical and epigenetic features, but cases include a discordant monozygotic twin pair, individuals with idiopathic developmental delay and autism, and families affected by infertility and reproductive wastage. NLRP5 mutations suggest connections between maternal reproductive fitness, early zygotic development and genomic imprinting. PMID:26323243

  17. Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research.

    PubMed

    Dymond, Simon; Dunsmoor, Joseph E; Vervliet, Bram; Roche, Bryan; Hermans, Dirk

    2015-09-01

    Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

  18. Scaling Behavior of Human Locomotor Activity Amplitude: Association with Bipolar Disorder

    PubMed Central

    Indic, Premananda; Salvatore, Paola; Maggini, Carlo; Ghidini, Stefano; Ferraro, Gabriella; Baldessarini, Ross J.; Murray, Greg

    2011-01-01

    Scale invariance is a feature of complex biological systems, and abnormality of multi-scale behaviour may serve as an indicator of pathology. The hypothalamic suprachiasmatic nucleus (SCN) is a major node in central neural networks responsible for regulating multi-scale behaviour in measures of human locomotor activity. SCN also is implicated in the pathophysiology of bipolar disorder (BD) or manic-depressive illness, a severe, episodic disorder of mood, cognition and behaviour. Here, we investigated scaling behaviour in actigraphically recorded human motility data for potential indicators of BD, particularly its manic phase. A proposed index of scaling behaviour (Vulnerability Index [VI]) derived from such data distinguished between: [i] healthy subjects at high versus low risk of mood disorders; [ii] currently clinically stable BD patients versus matched controls; and [iii] among clinical states in BD patients. PMID:21655197

  19. Past, present, and future of craniofacial superimposition: Literature and international surveys.

    PubMed

    Huete, Maria Isabel; Ibáñez, Oscar; Wilkinson, Caroline; Kahana, Tzipi

    2015-07-01

    In this manuscript, the past, present and future of the identification of human remains based on craniofacial superimposition is reviewed. An analysis of the different technological approaches developed over time is offered in conjunction with a new classification based on the technology implemented throughout the diverse phases of the process. The state of the art of the technique, in the academic and forensic realms, is reflected in an extensive international survey that includes over one hundred experts worldwide. The results of the survey indicate the current relative importance of the technique, despite of its controversial nature within the scientific community. Finally, the future challenges to be faced to justify the use of this technique for either profiling, exclusion or identification purposes are discussed.

  20. Regional isolation in the Balkan region: an analysis of craniofacial variation.

    PubMed

    Ross, Ann H

    2004-05-01

    Biological variation is investigated among contemporary Croatians, Bosnians, American whites, and other multitemporal Balkan populations (World War II Croatians, Macedonians, and Greeks) via multivariate statistics and distance measures of the craniofacial complex. This study demonstrates that there is considerable variation among groups of European ancestry. Bosnians and Croatians who are thought to be relatively homogenous and historically to originate from the same Slav ancestry show local variations. While environmental plasticity has been used to explain cranial changes among human groups, it does not adequately explain the variation observed between Bosnians and Croatians. It is an oversimplification to exclusively attribute the vast range of variability observed among local as well as geographic populations to environmental adaptations.