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

PubMed

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

2016-11-01

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

Dental and craniofacial characteristics in a patient with Dubowitz syndrome: a case report.

PubMed

Ballini, Andrea; Cantore, Stefania; Tullo, Domenica; Desiate, Apollonia

2011-01-27

Dubowitz syndrome is a very rare, autosomal recessive disease characterized by microcephaly, growth retardation, a high sloping forehead, facial asymmetry, blepharophimosis, sparse hair and eyebrows, low-set ears and mental retardation. Symptoms vary between patients, but other characteristics include a soft high-pitched voice, dental and craniofacial abnormalities, partial webbing of the fingers and toes, palate deformations, genital abnormalities, eczema, hyperactivity, preference for concrete over abstract thinking, language difficulties and an aversion to crowds. We describe the craniofacial and dental characteristics of a 12-year-old Caucasian Italian boy with both the typical and less common findings of Dubowitz syndrome. Diagnosis of Dubowitz syndrome is mainly based on the facial phenotype. Possible conditions for differential diagnosis include Bloom syndrome, Smith-Lemli-Opitz syndrome, and fetal alcohol syndrome. As there are few reports of this syndrome in the literature, we hope this case report will enable health professionals to recognize the phenotypic alterations of this syndrome, and allow early referral for the necessary multidisciplinary treatments.

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

PubMed

Sakai, Daisuke; Trainor, Paul A

2016-09-01

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

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

PubMed Central

Sakai, Daisuke; Trainor, Paul A.

2016-01-01

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

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

Craniofacial and Dental Development in Costello Syndrome

PubMed Central

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

2014-01-01

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

Craniofacial and dental development in Costello syndrome.

PubMed

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

2014-06-01

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

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.

Dissection of the complex genetic basis of craniofacial anomalies using haploid genetics and interspecies hybrids in Nasonia wasps

PubMed Central

Werren, John H.; Cohen, Lorna B.; Gadau, Juergen; Ponce, Rita; Baudry, Emmanuelle; Lynch, Jeremy A.

2016-01-01

The animal head is a complex structure where numerous sensory, structural and alimentary structures are concentrated and integrated, and its ontogeny requires precise and delicate interactions among genes, cells, and tissues. Thus, it is perhaps unsurprising that craniofacial abnormalities are among the most common birth defects in people, or that these defects have a complex genetic basis involving interactions among multiple loci. Developmental processes that depend on such epistatic interactions become exponentially more difficult to study in diploid organisms as the number of genes involved increases. Here, we present hybrid haploid males of the wasp species pair Nasonia vitripennis and Nasonia giraulti, which have distinct male head morphologies, as a genetic model of craniofacial development that possesses the genetic advantages of haploidy, along with many powerful genomic tools. Viable, fertile hybrids can be made between the species, and quantitative trail loci related to shape differences have been identified. In addition, a subset of hybrid males show head abnormalities, including clefting at the midline and asymmetries. Crucially, epistatic interactions among multiple loci underlie several developmental differences and defects observed in the F2 hybrid males. Furthermore, we demonstrate an introgression of a chromosomal region from N. giraulti into N. vitripennis that shows an abnormality in relative eye size, which maps to a region containing a major QTL for this trait. Therefore, the genetic sources of head morphology can, in principle, be identified by positional cloning. Thus, Nasonia is well positioned to be a uniquely powerful model invertebrate system with which to probe both development and complex genetics of craniofacial patterning and defects. PMID:26721604

Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein Treacle.

PubMed

Dixon, Jill; Dixon, Michael James

2004-04-01

Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in TCOF1, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated Tcof1 heterozygous mice on a mixed C57BL/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain-dependent phenotypes that range from extremely severe and lethal in a mixed CBA/Ca and 129 background, to apparently normal and viable in a mixed BALB/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA-derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the Tcof1 phenotype. Copyright 2004 Wiley-Liss, Inc.

[Roberts-SC phocomelia syndrome].

PubMed

Musfeld, D A; Bühler, E M; Heinzl, S

2001-01-01

The Roberts-SC phocomelia syndrome is a rare autosomal recessive inherited disorder clinically manifested by tetraphocomelia, pre- and postnatal growth retardation, and craniofacial abnormalities (skull, eyes, lip, and palate), accompanied at times by centromer puffing and splitting, renal abnormalities, heart defect, clitoral or penile enlargement, and bilateral corneal opacities. Mental retardation is common in surviving patients.

Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome.

PubMed

Eason, Jessica; Williams, Antionette L; Chawla, Bahaar; Apsey, Christian; Bohnsack, Brenda L

2017-09-01

Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest. Zebrafish eye and neural crest development was analyzed by means of live imaging, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, immunostaining, detection of reactive oxygen species, and in situ hybridization. Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development. Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome. Birth Defects Research 109:1212-1227, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2018-03-01

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

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

PubMed Central

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

2013-01-01

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

Concise Review: Personalized Human Bone Grafts for Reconstructing Head and Face

PubMed Central

Bhumiratana, Sarindr

2012-01-01

Regeneration of normal shape, architecture, and function of craniofacial tissues following congenital abnormality, trauma, or surgical treatment presents special problems to tissue engineering. Because of the great variations in properties of these tissues, currently available treatment options fall short of adequate care. We propose that the engineering of personalized bone graft customized to the patient and the specific clinical condition would revolutionize the way we currently treat craniofacial defects and discuss some of the current and emerging treatment modalities. PMID:23197642

[Head posture in orthodontics: physiopathology and clinical aspects 2].

PubMed

Caltabiano, M; Verzi, P; Scire Scappuzzo, G

1989-01-01

The Authors review in orthodontic respects present knowledges about head posture involvement in craniofacial morphogenesis and pathology. Relationships between craniofacial morphology, craniocervical posture, craniomandibular posture, cervical spine curvature, hyoid bone position and posture of whole body in space are shown, in attempt to explain conditions such as "forward head posture", mouth breathing and some occlusal disorders. Main methods to evaluate craniocervical relations on lateral skull radiographs are analysed. Pathogenesis of pain syndromes associated with abnormal craniocervical and craniomandibular mechanics are also briefly treated.

Hair Loss (Alopecia)

MedlinePlus

... Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental ... with certain abnormalities of the nails and the teeth. Later in childhood, hair loss may be due ...

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

PubMed Central

Rossello, Ricardo A.; Kohn, David H.

2009-01-01

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

Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice

PubMed Central

Yang, Ling; Gu, Shuping; Ye, Wenduo; Song, Yingnan; Chen, YiPing

2016-01-01

Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa. PMID:26553654

Genetics Home Reference: Simpson-Golabi-Behmel syndrome

MedlinePlus

... Wilms tumor and a cancerous tumor called a neuroblastoma that arises from developing nerve cells. Related Information ... Heart Defects Health Topic: Craniofacial Abnormalities Health Topic: Neuroblastoma Health Topic: Wilms Tumor Genetic and Rare Diseases ...

Multidisciplinary care of craniosynostosis

PubMed Central

Buchanan, Edward P; Xue, Yunfeng; Xue, Amy S; Olshinka, Asaf; Lam, Sandi

2017-01-01

The management of craniosynostosis, especially in the setting of craniofacial syndromes, is ideally done in a multidisciplinary clinic with a team focused toward comprehensive care. Craniosynostosis is a congenital disorder of the cranium, caused by the premature fusion of one or more cranial sutures. This fusion results in abnormal cranial growth due to the inability of the involved sutures to accommodate the growing brain. Skull growth occurs only at the patent sutures, resulting in an abnormal head shape. If cranial growth is severely restricted, as seen in multisuture craniosynostosis, elevation in intracranial pressure can occur. Whereas most patients treated in a multidisciplinary craniofacial clinic have non-syndromic or isolated craniosynostosis, the most challenging patients are those with syndromic craniosynostosis. The purpose of this article was to discuss the multidisciplinary team care required to treat both syndromic and non-syndromic craniosynostosis. PMID:28740400

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

Antenatal diagnosis of complete facial duplication--a case report of a rare craniofacial defect.

PubMed

Rai, V S; Gaffney, G; Manning, N; Pirrone, P G; Chamberlain, P F

1998-06-01

We report a case of the prenatal sonographic detection of facial duplication, the diprosopus abnormality, in a twin pregnancy. The characteristic sonographic features of the condition include duplication of eyes, mouth, nose and both mid- and anterior intracranial structures. A heart-shaped abnormality of the cranial vault should prompt more detailed examination for other supportive features of this rare condition.

Simpson-Golabi-Behmel syndrome types I and II.

PubMed

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

2014-09-20

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

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

Glycopyrrolate-induced craniofacial compensatory hyperhidrosis successfully treated with oxybutynin: report of a novel adverse effect and subsequent successful treatment.

PubMed

Prouty, Megan E; Fischer, Ryan; Liu, Deede

2016-10-15

Hyperhidrosis, or abnormally increased sweating, is a condition that may have a primary or secondary cause. Usually medication- induced secondary hyperhidrosis manifests with generalized, rather than focal sweating. We report a 32-year-old woman with a history of palmoplantar hyperhidrosis for 15 years who presented for treatment and was prescribed oral glycopyrrolate. One month later, the palmoplantar hyperhidrosis had resolved, but she developed new persistent craniofacial sweating. After an unsuccessful trial of clonidine, oxybutynin resolved the craniofacial hyperhidrosis. To our knowledge, this is the first case of compensatory hyperhidrosis secondary to glycopyrrolate reported in the literature. The case highlights the importance of reviewing medication changes that correlate with new onset or changing hyperhidrosis. It also demonstrates a rare drug adverse effect with successful treatment.

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.

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

PubMed

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

2000-06-12

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

Brief Report: Acrocallosal Syndrome and Autism

ERIC Educational Resources Information Center

Steiner, Carlos Eduardo; Guerreiro, Marilisa Mantovani; Marques-de-Faria, Antonia Paula

2004-01-01

The authors describe a boy presenting with acrocallosal syndrome and autism. Clinical features included craniofacial dysmorphisms, polydactyly, and mental retardation, besides behavioral symptoms compatible with autism. Neuroimaging revealed hypoplasia of the corpus callosum and cerebellar abnormalities. The role of this entity and other…

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

A review of hedgehog signaling in cranial bone development

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-10-06

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

FAF1, a Gene that Is Disrupted in Cleft Palate and Has Conserved Function in Zebrafish

PubMed Central

Ghassibe-Sabbagh, Michella; Desmyter, Laurence; Langenberg, Tobias; Claes, Filip; Boute, Odile; Bayet, Bénédicte; Pellerin, Philippe; Hermans, Karlien; Backx, Liesbeth; Mansilla, Maria Adela; Imoehl, Sandra; Nowak, Stefanie; Ludwig, Kerstin U.; Baluardo, Carlotta; Ferrian, Melissa; Mossey, Peter A.; Noethen, Markus; Dewerchin, Mieke; François, Geneviève; Revencu, Nicole; Vanwijck, Romain; Hecht, Jacqueline; Mangold, Elisabeth; Murray, Jeffrey; Rubini, Michele; Vermeesch, Joris R.; Poirel, Hélène A.; Carmeliet, Peter; Vikkula, Miikka

2011-01-01

Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, including cleft lip and palate. Clefts are the most common congenital craniofacial defects. Patients have complications with feeding, speech, hearing, and dental and psychological development. Affected by both genetic predisposition and environmental factors, the complex etiology of clefts remains largely unknown. Here we show that Fas-associated factor-1 (FAF1) is disrupted and that its expression is decreased in a Pierre Robin family with an inherited translocation. Furthermore, the locus is strongly associated with cleft palate and shows an increased relative risk. Expression studies show that faf1 is highly expressed in zebrafish cartilages during embryogenesis. Knockdown of zebrafish faf1 leads to pharyngeal cartilage defects and jaw abnormality as a result of a failure of CNC to differentiate into and express cartilage-specific markers, such as sox9a and col2a1. Administration of faf1 mRNA rescues this phenotype. Our findings therefore identify FAF1 as a regulator of CNC differentiation and show that it predisposes humans to cleft palate and is necessary for lower jaw development in zebrafish. PMID:21295280

Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development.

PubMed

Foerst-Potts, L; Sadler, T W

1997-05-01

In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are expressed during critical stages of neural tube, neural crest, and craniofacial development, suggesting that these genes play important roles in organogenesis and cell differentiation. Although the patterns of expression are intriguing, little is known about the function of these genes in vertebrate embryonic development. Therefore, the expression of both genes, separately and together, was disrupted using antisense oligodeoxynucleotides and whole embryo culture techniques. Antisense attenuation of Msx-1 during early stages of neurulation produced hypoplasia of the maxillary, mandibular, and frontonasal prominences, eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of enlarged optic vesicles, which may ultimately result in micropthalmia similar to that observed in Small eye mice homozygous for mutations in the Pax-6 gene. Histological sections and SEM analysis revealed a thinning of the neuroepithelium in the diencephalon and optic vesicle and mesenchymal deficiencies in the craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced similar malformations as those targeting Msx-1, with the exception that there was an increase in number and severity of neural tube and somite defects. Embryos injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides showed no novel abnormalities, suggesting that the genes do not operate in a redundant manner.

Genetics Home Reference: lattice corneal dystrophy type II

MedlinePlus

... lattice corneal dystrophy type II can have a facial expression that appears sad. Related Information What does it ... links) Children's Craniofacial Association: A Guide to Understanding Facial ... pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment. Hum Mol Genet. ...

FGFR3 mutation causes abnormal membranous ossification in achondroplasia.

PubMed

Di Rocco, Federico; Biosse Duplan, Martin; Heuzé, Yann; Kaci, Nabil; Komla-Ebri, Davide; Munnich, Arnold; Mugniery, Emilie; Benoist-Lasselin, Catherine; Legeai-Mallet, Laurence

2014-06-01

FGFR3 gain-of-function mutations lead to both chondrodysplasias and craniosynostoses. Achondroplasia (ACH), the most frequent dwarfism, is due to an FGFR3-activating mutation which results in impaired endochondral ossification. The effects of the mutation on membranous ossification are unknown. Fgfr3(Y367C/+) mice mimicking ACH and craniofacial analysis of patients with ACH and FGFR3-related craniosynostoses provide an opportunity to address this issue. Studying the calvaria and skull base, we observed abnormal cartilage and premature fusion of the synchondroses leading to modifications of foramen magnum shape and size in Fgfr3(Y367C/+) mice, ACH and FGFR3-related craniosynostoses patients. Partial premature fusion of the coronal sutures and non-ossified gaps in frontal bones were also present in Fgfr3(Y367C/+) mice and ACH patients. Our data provide strong support that not only endochondral ossification but also membranous ossification is severely affected in ACH. Demonstration of the impact of FGFR3 mutations on craniofacial development should initiate novel pharmacological and surgical therapeutic approaches.

Anaesthetic management of a parturient with Laron syndrome.

PubMed

Bhatia, K; Cockerham, R

2011-10-01

We report a case of a parturient with Laron syndrome, a rare form of dwarfism which results from an inability to generate insulin-like growth factor 1. In addition to dwarfism these patients may have craniofacial abnormalities, atlantoaxial instability, spinal stenosis and metabolic, musculoskeletal and genitourinary abnormalities. The patient underwent an urgent caesarean section using combined spinal-epidural anaesthesia. Laron syndrome is reviewed and its anaesthetic implications discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Craniofacial anomalies associated with hypospadias. Description of a hospital based population in South America.

PubMed

Fernandez, Nicolas; Escobar, Rebeca; Zarante, Ignacio

2016-01-01

Hypospadias is a congenital abnormality of the penis, in which there is incomplete development of the distal urethra. There are numerous reports showing na increase of prevalence of hypospadias. Association of craniofacial malformations in patients diagnosed with hypospadias is rare. The aim of this study is to describe the association between hypospadias and craniofacial congenital anomalies. A retrospective review of the Latin-American collaborative study of congenital malformations (ECLAMC) data was performed between January 1982 and December 2011. We included children diagnosed with associated hypospadias and among them we selected those that were associated with any craniofacial congenital anomaly. Global prevalence was 11.3 per 10.000 newborns. In this population a total of 809 patients with 1117 associated anomalies were identified. On average there were 1.7 anomalies per patient. Facial anomalies were present in 13.2%. The most commonly major facial anomaly associated to hypospadias was cleft lip/palate with 52 cases. We identified that 18% have an association with other anomalies, and found an association between craniofacial anomalies and hypospadias in 0.59 cases/10.000 newborns. Hypospadias is the most common congenital anomaly affecting the genitals. Its association with other anomalies is rare. It has been reported that other malformations occur in 29.3% of the cases with hypospadias. The more proximal the meatus, the higher the risk for having another associated anomaly. Associated hypospadias are rare, and it is important to identify the concurrent occurrence of craniofacial anomalies to better treat patients that might need a multidisciplinary approach. Copyright© by the International Brazilian Journal of Urology.

Craniofacial anomalies associated with hypospadias. Description of a hospital based population in South America

PubMed Central

Fernandez, Nicolas; Escobar, Rebeca; Zarante, Ignacio

2016-01-01

ABSTRACT Introduction: Hypospadias is a congenital abnormality of the penis, in which there is incomplete development of the distal urethra. There are numerous reports showing an increase of prevalence of hypospadias. Association of craniofacial malformations in patients diagnosed with hypospadias is rare. The aim of this study is to describe the association between hypospadias and craniofacial congenital anomalies. Materials and Methods: A retrospective review of the Latin-American collaborative study of congenital malformations (ECLAMC) data was performed between January 1982 and December 2011. We included children diagnosed with associated hypospadias and among them we selected those that were associated with any craniofacial congenital anomaly. Results: Global prevalence was 11.3 per 10.000 newborns. In this population a total of 809 patients with 1117 associated anomalies were identified. On average there were 1.7 anomalies per patient. Facial anomalies were present in 13.2%. The most commonly major facial anomaly associated to hypospadias was cleft lip/palate with 52 cases. We identified that 18% have an association with other anomalies, and found an association between craniofacial anomalies and hypospadias in 0.59 cases/10.000 newborns. Discussion: Hypospadias is the most common congenital anomaly affecting the genitals. Its association with other anomalies is rare. It has been reported that other malformations occur in 29.3% of the cases with hypospadias. The more proximal the meatus, the higher the risk for having another associated anomaly. Conclusion: Associated hypospadias are rare, and it is important to identify the concurrent occurrence of craniofacial anomalies to better treat patients that might need a multidisciplinary approach. PMID:27564292

Inter-examiner agreement of the systematic physical examination in patients with obstructive sleep disorders.

PubMed

Sguillar, Danilo Anunciatto; de Aguiar Vidigal, Tatiana; Mangussi, João Paulo; Bittencourt, Lia; Gregório, Luiz Carlos; Tufik, Sergio; Haddad, Fernanda Louise Martinho

2016-12-01

The goal of this study was to investigate the agreement between examiners who were or were not trained in the physical examination of the upper airway (UA) and the craniofacial skeleton of individuals with obstructive sleep disorders (OSD). A systematic assessment of the UA and craniofacial skeleton was performed on 55 individuals with OSD. The participants were consecutively assessed by three otorhinolaryngologists who specialized in sleep medicine for at least 1 year (trained examiners) and two doctors who were attending a residency program in otorhinolaryngology (untrained examiners). When analyzing all of the parameters assessed, the concordance was better in the trained group (k = 0.694, which is considered "good") compared to the untrained group (k = 0.475, "fair") (p < 0.001). The inter-examiner agreement was also better in the trained compared to the untrained group, as follows: craniofacial (k = 0.643 vs. 0.349), nasal (k = 0.657 vs. 0.614), and pharyngeal (k = 0.729 vs. 0.276) abnormalities (p < 0.05). The overall concordance of the physical examination of the UA and craniofacial skeleton was "good" among the trained specialists and "fair" among examiners without appropriate training, despite its subjectivity.

The 3-M syndrome. A heritable low birthweight dwarfism.

PubMed

Van Goethem, H; Malvaux, P

1987-10-01

Two male siblings and one girl with the 3-M syndrome are reported. The main clinical features include low birthweight, proportionate dwarfism, hatched-shaped cranio-facial configuration, abnormalities of mouth and teeth, short broad neck with prominent trapezius, pectus deformity, transverse grooves of anterior chest, and winged scapulae.

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

PubMed

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

2008-02-01

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

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

PubMed

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

2008-09-15

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

Hypophosphatemic rickets and craniosynostosis: a multicenter case series.

PubMed

Vega, Rafael A; Opalak, Charles; Harshbarger, Raymond J; Fearon, Jeffrey A; Ritter, Ann M; Collins, John J; Rhodes, Jennifer L

2016-06-01

OBJECTIVE This study examines a series of patients with hypophosphatemic rickets and craniosynostosis to characterize the clinical course and associated craniofacial anomalies. METHODS A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers. Parameters examined included sex, age at diagnosis of head shape anomaly, affected sutures, etiology of rickets, presenting symptoms, number and type of surgical interventions, and associated diagnoses. A review of the literature was performed to optimize treatment recommendations. RESULTS Ten patients were identified (8 males, 2 females). Age at presentation ranged from 1 to 9 years. The most commonly affected suture was the sagittal (6/10 patients). Etiologies included antacid-induced rickets, autosomal dominant hypophosphatemic rickets, and X-linked hypophosphatemic (XLH) rickets. Nine patients had undergone at least 1 cranial vault remodeling (CVR) surgery. Three patients underwent subsequent surgeries in later years. Four patients underwent formal intracranial pressure (ICP) monitoring, 3 of which revealed elevated ICP. Three patients were diagnosed with a Chiari Type I malformation. CONCLUSIONS Secondary craniosynostosis develops postnatally due to metabolic or mechanical factors. The most common metabolic cause is hypophosphatemic rickets, which has a variety of etiologies. Head shape changes occur later and with a more heterogeneous presentation compared with that of primary craniosynostosis. CVR may be required to prevent or relieve elevated ICP and abnormalities of the cranial vault. Children with hypophosphatemic rickets who develop head shape abnormalities should be promptly referred to a craniofacial specialist.

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.

Grainyhead-like 3 regulation of endothelin-1 in the pharyngeal endoderm is critical for growth and development of the craniofacial skeleton.

PubMed

Dworkin, Sebastian; Simkin, Johanna; Darido, Charbel; Partridge, Darren D; Georgy, Smitha R; Caddy, Jacinta; Wilanowski, Tomasz; Lieschke, Graham J; Doggett, Karen; Heath, Joan K; Jane, Stephen M

2014-08-01

Craniofacial development is a highly conserved process that requires complex interactions between neural crest cells (NCCs) and pharyngeal tissues derived from all three germ layers. Signals emanating from the pharyngeal endoderm drive differentiation of NCCs into craniofacial cartilage, and disruption of this process underpins several human craniofacial defects (CFD). Here, we demonstrate that morpholino (MO)-mediated knockdown in zebrafish of the highly conserved transcription factor grainyhead-like 3 (grhl3), which is selectively expressed in the pharyngeal endoderm, leads to severe hypoplasia of the lower jaw cartilages. Phylogenetic analysis of conserved grhl-binding sites in gene regulatory regions identified endothelin-1 (edn1) as a putative direct grhl3 target gene, and this was confirmed by chromatin precipitation (ChIP) assays in zebrafish embryos. Injection of sub-phenotypic concentrations of MOs targeting both grhl3 and edn1 induced jaw abnormalities, and injection of edn1 mRNA into grhl3-morphants rescued both pharyngeal expression of the downstream effectors of edn1, and jaw cartilage formation. This study sheds new light on the role of endodermal endothelin-1 in vertebrate jaw development, and highlights potential new genetic defects that could underpin human CFD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Morpholino-based screen to identify novel genes involved in craniofacial morphogenesis

PubMed Central

Melvin, Vida Senkus; Feng, Weiguo; Hernandez-Lagunas, Laura; Artinger, Kristin Bruk; Williams, Trevor

2014-01-01

BACKGROUND The regulatory mechanisms underpinning facial development are conserved between diverse species. Therefore, results from model systems provide insight into the genetic causes of human craniofacial defects. Previously, we generated a comprehensive dataset examining gene expression during development and fusion of the mouse facial prominences. Here, we used this resource to identify genes that have dynamic expression patterns in the facial prominences, but for which only limited information exists concerning developmental function. RESULTS This set of ~80 genes was used for a high throughput functional analysis in the zebrafish system using Morpholino gene knockdown technology. This screen revealed three classes of cranial cartilage phenotypes depending upon whether knockdown of the gene affected the neurocranium, viscerocranium, or both. The targeted genes that produced consistent phenotypes encoded proteins linked to transcription (meis1, meis2a, tshz2, vgll4l), signaling (pkdcc, vlk, macc1, wu:fb16h09), and extracellular matrix function (smoc2). The majority of these phenotypes were not altered by reduction of p53 levels, demonstrating that both p53 dependent and independent mechanisms were involved in the craniofacial abnormalities. CONCLUSIONS This Morpholino-based screen highlights new genes involved in development of the zebrafish craniofacial skeleton with wider relevance to formation of the face in other species, particularly mouse and human. PMID:23559552

A role for chemokine signaling in neural crest cell migration and craniofacial development

PubMed Central

Killian, Eugenia C. Olesnicky; Birkholz, Denise A.; Artinger, Kristin Bruk

2009-01-01

Neural crest cells (NCCs) are a unique population of multipotent cells that migrate along defined pathways throughout the embryo and give rise to many diverse cell types including pigment cells, craniofacial cartilage and the peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide variety of congenital birth defects including craniofacial abnormalities. The chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key components in the regulation of cell migration in a variety of tissues. Here we describe a novel role for the zebrafish chemokine receptor Cxcr4a in the development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a, but not Cxcr7b results in aberrant CNCC migration, defects in the neurocranium, as well as cranial ganglia dismorphogenesis. Moreover, overexpression of either Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic craniofacial cartilages. We propose a model in which Sdf1b signaling from the pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important for both the proper condensation of the CNCCs into pharyngeal arches and the subsequent patterning and morphogenesis of the neural crest derived tissues. PMID:19576198

Osteoglophonic dwarfism in two generations.

PubMed Central

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

1983-01-01

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

Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder

ERIC Educational Resources Information Center

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

2017-01-01

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

Placento-Cranial Adhesions in Amniotic Band Syndrome and the Role of Surgery in Their Management: An Unusual Case Presentation and Systematic Literature Review.

PubMed

Menekse, Guner; Mert, Mustafa Kurthan; Olmaz, Burak; Celik, Tamer; Celik, Umit Sizmaz; Okten, Ali Ihsan

2015-01-01

Amniotic band syndrome is a group of sporadic congenital anomalies that involve the limbs, craniofacial regions and trunk, ranging from simple digital band constriction to complex craniofacial and central nervous system abnormalities. Placento-cranial adhesions in amniotic band syndrome are extremely rare, and severe conditions are associated with high morbidity and mortality rates. In this study, we pooled placento-cranial adhesion case reports that were published in the medical literature and added an unpublished case from our institution. The purpose of this article was to review and discuss the clinical features and outcomes of placento-cranial adhesions in amniotic band syndrome. © 2015 S. Karger AG, Basel.

Abnormal Variations in the Facial Soft Tissues of Individuals With Down Syndrome: Sudan Versus Italy.

PubMed

Sforza, Chiarella; Dolci, Claudia; Dellavia, Claudia; Gibelli, Daniele M; Tartaglia, Gianluca M; Elamin, Fadil

2015-09-01

To provide quantitative information about the facial soft tissue of Italian and Northern Sudanese subjects with Down syndrome by using summary anthropometric measurements. The three-dimensional coordinates of soft tissue facial landmarks were obtained using a computerized digitizer in 54 Italian subjects with Down syndrome (20 females and 34 males, 13 to 52 years), in 64 Northern Sudanese subjects with Down syndrome (18 females and 46 males, 5 to 34 years), and in 578 Italian and 653 Northern Sudanese reference subjects, matched for sex and age. From the landmarks, 16 facial dimensions were calculated. Data from subjects with Down syndrome were compared with those collected from control individuals by computing z scores. Two summary anthropometric measurements for quantifying craniofacial variations were obtained: the mean z score (an index of overall facial size) and its standard deviation, the craniofacial variability index (an index of facial harmony). In subjects with Down syndrome, facial size was significantly smaller and craniofacial variability was significantly greater than in typically developed individuals; 93% of Italian and 81% of Northern Sudanese subjects with Down syndrome had one or both values outside the normal interval. Overall, Italian subjects with Down syndrome differed more from the norm than did those from Northern Sudan. In the Northern Sudanese subjects, the mean z scores and the craniofacial variability index were significantly influenced by age: Older Northern Sudanese subjects with Down syndrome had smaller mean z scores and craniofacial variability index values than younger subjects. The two ethnic groups had different alterations in their soft tissue facial dimensions that were partially influenced by age.

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

PubMed

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

2006-09-05

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

Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome

ClinicalTrials.gov

2018-03-30

Freeman-Sheldon Syndrome; Arthrogryposis Distal Type 2A; Whistling Face Syndrome; Craniocarpotarsal Dysplasia; Craniocarpotarsal Dystrophy; Freeman-Sheldon Syndrome Variant; Sheldon-Hall Syndrome; Arthrogryposis Distal Type 2B; Gordon Syndrome; Arthrogryposis Distal Type 3; Arthrogryposis Distal Type 1; Arthrogryposis, Distal, Type 1A; Arthrogryposis Distal Type 1B; Arthrogryposis, Distal; Craniofacial Abnormalities; Arthrogryposis

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

PubMed Central

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

2010-01-01

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

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

PubMed Central

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

2014-01-01

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

[Partial facial duplication (a rare diprosopus): Case report and review of the literature].

PubMed

Es-Seddiki, A; Rkain, M; Ayyad, A; Nkhili, H; Amrani, R; Benajiba, N

2015-12-01

Diprosopus, or partial facial duplication, is a very rare congenital abnormality. It is a rare form of conjoined twins. Partial facial duplication may be symmetric or not and may involve the nose, the maxilla, the mandible, the palate, the tongue and the mouth. A male newborn springing from inbred parents was admitted at his first day of life for facial deformity. He presented with hypertelorism, 2 eyes, a tendency to nose duplication (flatted large nose, 2 columellae, 2 lateral nostrils separated in the midline by a third deformed hole), two mouths and a duplicated maxilla. Laboratory tests were normal. The cranio-facial CT confirmed the maxillary duplication. This type of cranio-facial duplication is a rare entity with about 35 reported cases in the literature. Our patient was similar to a rare case of living diprosopus reported by Stiehm in 1972. Diprosopus is often associated with abnormalities of the gastrointestinal tract, the central nervous system, the cardiovascular and respiratory systems and with a high incidence of cleft lip and palate. Surgical treatment consists in the resection of the duplicated components. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

PubMed Central

Hernandez, Jose A.; Gonzalez, Cesar G.

2017-01-01

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

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

PubMed Central

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

2006-01-01

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

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

PubMed

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

2014-01-01

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

A trend toward smaller optical angles and medial-ocular distance in schizophrenia spectrum, but not in bipolar and major depressive disorders.

PubMed

Wang, Yi; Deng, Yi; Li, Zhi; Li, Xu; Zhang, Chen-Yuan; Jin, Zhen; Fan, Ming-Xia; Compton, Michael T; Cheung, Eric F C; Lim, Kelvin O; Chan, Raymond C K

2016-12-01

Minor physical anomalies (MPAs) are subtle signs of fetal developmental abnormalities that have been considered to be among the most replicated risk markers for schizophrenia-spectrum disorders. However, quantitative approaches are needed to measure craniofacial MPAs. The present study adopted an imaging-based quantitative approach to examine craniofacial MPAs across the spectrum of schizophrenia and affective disorders, to address their sensitivity and specificity. We sampled 31 patients with schizophrenia, 30 of their unaffected relatives, and 30 individuals with schizotypal personality traits, as well as 37 non-schizotypal controls. We also examined 17 patients with bipolar disorder and 19 patients with major depressive disorder. Five craniofacial MPAs were measured on anterior-posterior commissure-aligned T1-weighted images of an individual's native brain space: medial-ocular distance, lateral-ocular distance, optical angle, maximum skull length, and skull-base width. Compared to non-schizotypal controls, patients with schizophrenia and their relatives showed a trend toward having smaller optical angles and medial-ocular distance, while no difference was found in patients with bipolar or major depressive disorders, suggesting some degree of specificity to schizophrenia. Our approach may benefit future research on craniofacial MPAs as risk markers for schizophrenia-spectrum disorders, and may eventually be useful in strategies to enhance risk stratification using multiple risk markers. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Role of Imaging and Cytogenetics in Evaluation of DiGeorge Syndrome - A Rare Entity in Clinical Practice.

PubMed

Ramachandran, Rajoo; Babu, Sellappan Rajamanickam; Ilanchezhian, Subramanian; Radhakrishnan, Prabhu Radhan

2015-01-01

DiGeorge syndrome is a congenital genetic disorder that affects the endocrine system, mainly the thymus and parathyroid glands. The syndrome produces different symptoms, which vary in severity and character between patients. It manifests with craniofacial dysmorphism and defects in the heart, parathyroid, and thymus. Patients can present with a palatal deformity and nasal speech. This rare entity is caused mainly due to deletion of chromosome 22q11.2. Radiographic evaluation of DiGeorge syndrome is necessary to define aberrant anatomy, evaluate central nervous system, craniofacial abnormalities, musculoskeletal system, and cardiothoracic contents. It also helps in planning surgical procedures and surgical reconstructions. We report a case of DiGeorge syndrome in a 4-month-old neonate and discuss the clinical, imaging, and cytogenetic findings that helped in the diagnosis of this rare entity.

A rare case of monozygotic iniodymic diprosopiasis in a German Holstein calf.

PubMed

Weber, Jim; Behn, Holger; Freick, Markus

2017-06-01

Craniofacial duplication abnormity is a rare phenomenon in buiatric practice. This report attends to a male German Holstein calf which could be classified as a diprosopic iniodymus. A fetus exhibiting a doubled face was delivered after fetotomy. To our knowledge, this is the first description of diprosopiasis with two cranial cavities as well as two separate encephala in a calf showing the potential extent of duplication. Throughout this work also the question is answered of whether this malformation in a bovine species arose from one embryo or rather, there is a dizygotic background by genotyping of tissue samples from both parts of the diprosopus. Regarding etiology, not only hereditary dispositions including among others a failed function of the signaling molecule Sonic hedgehog mediating regulation of craniofacial morphogenesis, but also incompletely separated monozygotic twins are discussed.

Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

PubMed

Kornreich, L; Horev, G; Schwarz, M; Karmazyn, B; Laron, Z

2002-04-01

To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

Bartsocas-papas syndrome: unusual findings in the first reported egyptian family.

PubMed

Abdalla, E M; Morsy, H

2011-01-01

Bartsocas-Papas syndrome (BPS) is an autosomal recessive syndrome with severe craniofacial, limb, and genital abnormalities. As of 2011, 24 published cases and families were registered in the Orphanet Report Series. Compared to other disorders characterized by pterygia, the condition is usually more severe and often lethal: most affected patients die in utero or shortly after birth. We report the first Egyptian family with Bartsocas-Papas syndrome comprising three cases; our proband who was a female infant with severe craniofacial and limb anomalies typical of Bartsocas-Papas syndrome, a similarly affected female fetus which died in utero at the 7th gestational month, and a 16-year-old mentally retarded uncle who presented with some of the typical features of Bartsocas-Papas syndrome, including syndactyly, thumb hypoplasia, and microphthalmia. This male patient actually did not present with pterygia, however, we find his clinical description noteworthy.

Prenatal diagnosis of isochromosome 20q in a fetus with vertebral anomaly and rocker-bottom feet.

PubMed

Receveur, Aline; Brisset, Sophie; Martinovic, Jelena; Bazin, Anne; Lhomann, Laurence; Colmant, Claire; Pineau, Dominique; Gautier, Valérie; Tosca, Lucie; Tachdjian, Gérard

2017-10-01

Isochromosome of the long arm of chromosome 20 (i(20q)) is a rare structural abnormality in prenatal diagnosis. Thirty prenatal cases of mosaic i(20q) have been reported, among which only four are associated with fetal malformations. We describe a new prenatal case of i(20q) with fetal malformations. We also observed a discrepancy between uncultured and cultured amniotic fluid cells by using conventional cytogenetic, fluorescence in situ hybridization and array-SNP analysis. The short arm deletion of chromosome 20 arising from the isochromosome encompassed two candidate genes PAX1 and JAG1 involved in cranio-facial and vertebral development. The data would allow establishing a phenotype-genotype correlation. Thus, we proposed to define a recognizable syndrome combining cranio-facial dysmorphism, vertebral bodies' anomalies, feet and cerebral malformations. Copyright © 2017. Published by Elsevier B.V.

Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia.

PubMed

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

2017-12-01

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

Implant rehabilitation for a patient with Hallerman-Streiff syndrome: a case report.

PubMed

Abadi, Behruz J; Van Sickels, Joseph E; McConnell, Thomas A; Kluemper, G Thomas

2009-01-01

Hallermann-Streiff syndrome is a rare genetic disorder characterized by craniofacial malformations, sparse hair, eye abnormalities, dental defects, degenerative skin changes, and short stature. The syndrome has many implications for dental treatment. Patients typically present with multiple missing and poorly formed teeth. The purpose of this case report is to discuss the overall management of a patient with Hallermann-Streiff syndrome by oral maxillofacial surgery, orthodontic treatment, and prosthodontic reconstruction.

Trends in medical malpractice claims in patients with cleft or craniofacial abnormalities in the United States.

PubMed

Rawal, Rounak B; Kilpatrick, Lauren A; Wood, Jeyhan S; Drake, Amelia F

2016-11-01

To describe medical malpractice trends in patients with cleft and/or craniofacial abnormalities. A modified Delphi approach was used to gather search terms. Search settings included "all jury verdicts and settlements", with jurisdiction of "all states" and "all federal courts" (by court and circuit). A retrospective review of WestLawNext legal database was conducted. Cases were excluded if they did not have a direct association from the patient's craniofacial anomaly or if they were not related to malpractice. Forty-two cases met inclusion criteria. Cases closed between 1981 and 2014 were included. The mean payment among claims with an indemnity payment was $3.9 million. Of cases brought to trial, 62% were in favor of the plaintiff. Amongst physicians named as co-defendants, pediatricians were most commonly named (24%), followed by plastic surgeons (16%), obstetricians (7.8%), and radiologists (7.8%). "Missed diagnosis" was the most common type of negligent claim (45%), followed by "surgical error" (21%), and "medication error" (17%). "Anoxic brain injury" resulted in the highest median indemnity payment for complication of patient management ($3.5 million), followed by "wrongful birth" ($1.03 million), and "minor physical injury" ($520,000). No specific type of negligent claim (p = 0.764) nor complication of patient management (p = 0.61) was associated with a greater indemnity payment. Mean indemnity payment was $920,000 prior to 2001 and $4.4 million after 2001 (p = 0.058). Mean indemnity payments were fourteen-fold greater in patients as compared to those in the overall population ($3.9 million versus $274,887) and seven-fold greater than those in the average pediatric population ($3.9 million versus $520,923). All healthcare providers should be aware of the associated medical malpractice claims that may be incurred when treating patients at risk for these conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature.

PubMed

Davidson, Tom B; Sanchez-Lara, Pedro A; Randolph, Linda M; Krieger, Mark D; Wu, Shi-Qi; Panigrahy, Ashok; Shimada, Hiroyuki; Erdreich-Epstein, Anat

2012-03-22

Pierre-Robin sequence (PRS) is defined by micro- and/or retrognathia, glossoptosis and cleft soft palate, either caused by deformational defect or part of a malformation syndrome. Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by mutations in the NF2 gene on chromosome 22q12.2. NF2 is characterized by bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas and ependymomas, and juvenile cataracts. To date, NF2 and PRS have not been described together in the same patient. We report a female with PRS (micrognathia, cleft palate), microcephaly, ocular hypertelorism, mental retardation and bilateral hearing loss, who at age 15 was also diagnosed with severe NF2 (bilateral cerebellopontine schwannomas and multiple extramedullary/intradural spine tumors). This is the first published report of an individual with both diagnosed PRS and NF2. High resolution karyotype revealed 46, XX, del(22)(q12.1q12.3), FISH confirmed a deletion encompassing NF2, and chromosomal microarray identified a 3,693 kb deletion encompassing multiple genes including NF2 and MN1 (meningioma 1).Five additional patients with craniofacial dysmorphism and deletion in chromosome 22-adjacent-to or containing NF2 were identified in PubMed and the DECIPHER clinical chromosomal database. Their shared chromosomal deletion encompassed MN1, PITPNB and TTC28. MN1, initially cloned from a patient with meningioma, is an oncogene in murine hematopoiesis and participates as a fusion gene (TEL/MN1) in human myeloid leukemias. Interestingly, Mn1-haploinsufficient mice have abnormal skull development and secondary cleft palate. Additionally, Mn1 regulates maturation and function of calvarial osteoblasts and is an upstream regulator of Tbx22, a gene associated with murine and human cleft palate. This suggests that deletion of MN1 in the six patients we describe may be causally linked to their cleft palates and/or craniofacial abnormalities. Thus, our report describes a NF2-adjacent chromosome 22q12.2 deletion syndrome and is the first to report association of MN1 deletion with abnormal craniofacial development and/or cleft palate in humans.

The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor.

PubMed

Valdez, Benigno C; Henning, Dale; So, Rolando B; Dixon, Jill; Dixon, Michael J

2004-07-20

Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized by an abnormality of craniofacial development that arises during early embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS have been uncovered, the mechanism underlying its pathogenesis and the function of treacle remain unknown. Here, we show that treacle is involved in ribosomal DNA gene transcription by interacting with upstream binding factor (UBF). Immunofluorescence labeling shows treacle and UBF colocalize to specific nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin d-treated HeLa cells. Biochemical analysis shows the association of treacle and UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both suggest physical interaction of the two nucleolar phosphoproteins. Down-regulation of treacle expression using specific short interfering RNA results in inhibition of ribosomal DNA transcription and cell growth. A similar correlation is observed in Tcof(+/-) mouse embryos that exhibit craniofacial defects and growth retardation. Thus, treacle haploinsufficiency in TCS patients might result in abnormal development caused by inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryogenesis. The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS.

The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor

PubMed Central

Valdez, Benigno C.; Henning, Dale; So, Rolando B.; Dixon, Jill; Dixon, Michael J.

2004-01-01

Treacher Collins syndrome (TCS) is an autosomal dominant disorder characterized by an abnormality of craniofacial development that arises during early embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the nucleolar phosphoprotein treacle. Even though the genetic alterations causing TCS have been uncovered, the mechanism underlying its pathogenesis and the function of treacle remain unknown. Here, we show that treacle is involved in ribosomal DNA gene transcription by interacting with upstream binding factor (UBF). Immunofluorescence labeling shows treacle and UBF colocalize to specific nucleolar organizer regions and cosegregate within nucleolar caps of actinomycin d-treated HeLa cells. Biochemical analysis shows the association of treacle and UBF with chromatin. Immunoprecipitation and the yeast two-hybrid system both suggest physical interaction of the two nucleolar phosphoproteins. Down-regulation of treacle expression using specific short interfering RNA results in inhibition of ribosomal DNA transcription and cell growth. A similar correlation is observed in Tcof+/- mouse embryos that exhibit craniofacial defects and growth retardation. Thus, treacle haploinsufficiency in TCS patients might result in abnormal development caused by inadequate ribosomal RNA production in the prefusion neural folds during the early stages of embryogenesis. The elucidation of a physiological function of treacle provides important information of relevance to the molecular dissection of the biochemical pathology of TCS. PMID:15249688

Craniofacial abnormalities in homozygous Small eye (Sey/Sey) embryos and newborn mice.

PubMed

Kaufman, M H; Chang, H H; Shaw, J P

1995-06-01

The Small eye (Sey) gene in the mouse is lethal in the homozygous state. It is located on chromosome 2, is a mutation in the Pax-6 gene, and is genetically homologous with the human aniridia 2 (AN2) gene mutation. Numerous studies over the last few years, using genetic and molecular biological approaches, have investigated both the location of the gene as well as its possible mode of action. In the homozygous state, the primary defect appears to be limited to the failure of differentiation of the presumptive lens and nasal placodes. Such mice therefore display a characteristic phenotype; they possess neither eyes nor any nasal derivatives. Their heterozygous (Sey/+) and normal (+/+) littermates may be distinguished before birth only by a detailed examination of their eyes. Few detailed morphological/histological studies have been undertaken to date in the Sey/Sey embryos and newborn, and in the present study we describe a variety of craniofacial abnormalities that have not previously been reported. We observed, with one exception, delayed closure of the palate, and the presence in 80% of mice of an abnormal complement of upper incisor teeth, so that 35% possessed 1 supernumerary tooth while 45% possessed 2 supernumerary teeth. In these mice, a total of either 3 or 4, rather than the normal complement of 2, upper incisor teeth were present. Possibly the most unexpected finding, however, was the presence of a median cartilaginous rod-like structure which protruded between the 2 maxillae to give the Alizarin red S and Alcian blue-stained 'cleared' skulls of the newborn mice a characteristic 'unicorn-like' appearance. While this structure appeared to be a rostral extension of the chondrocranium, its exact derivation is unclear.

[Alobar holoprosencephaly associated with diabetes insipidus and hypothyroidism in a 10-month old infant].

PubMed

Seck, Ndiogou; Basse, Idrissa; Keita, Younoussa; Boiro, Djiril; Thiam, Lamine; Ndongo, Aliou Adoulaye; Diagne, Ibrahima

2017-01-01

Holoprosencephaly (HPE) is a serious brain malformation due to a failure of medial forebrain cleavage. This is an abnormality which is more often associated with craniofacial malformations, psychomotor development delay, diabetes insipidus and variable endocrine disorders. It is due to different causes including chromosomal abnormalities (trisomy 13, 18)and polymalformative syndromes (CHARGE Syndrome). Diagnosis is based on brain imaging. A few rare cases have been described in the literature. We here report the case of alobar HPE in a 10-month old infant. Diagnosis was based on cerebral CT scan performed due to delayed psychomotor development and in the absence of visible malformations. Endocrine assessment allowed to detect central diabetes insipidus and central hypothyroidism, probably of hypothalamic origin.

K-RasV14I recapitulates Noonan syndrome in mice

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

Craniofacial and pharyngeal airway morphology in patients with acromegaly.

PubMed

Balos Tuncer, Burcu; Canigur Bavbek, Nehir; Ozkan, Cigdem; Tuncer, Cumhur; Eroglu Altinova, Alev; Gungor, Kahraman; Akturk, Mujde; Balos Toruner, Fusun

2015-08-01

The aim of this study was to assess differences in craniofacial characteristics, upper spine and pharyngeal airway morphology in patients with acromegaly compared with healthy individuals. Twenty-one patients with acromegaly were compared with 22 controls by linear and angular measurements on cephalograms. The differences between the mean values of cephalometric parameters were analyzed with Mann-Whitney U-test. With respect to controls, anterior (p<0.05), middle (p<0.01) and posterior (p<0.05) cranial base lengths were increased, sella turcica was enlarged (p<0.001) and upper spine morphology demonstrated differences in the height of atlas (p<0.01) and axis (p<0.05) in patients with acromegaly. Craniofacial changes were predominantly found in the frontal bone (p<0.01) and the mandible (p<0.05). As for the airway, patients with acromegaly exhibited diminished dimensions at nasal (p<0.001), uvular (p<0.01), mandibular (p<0.01) pharyngeal levels and at the narrowest point of the pharyngeal airway space (p<0.001) compared to healthy controls. Soft palate width was significantly higher (p<0.001) and the hyoid bone was more vertically positioned (p<0.01) in patients with acromegaly. Current results point to the importance of the reduced airway dimensions and that dentists and/or orthodontists should be aware of the cranial or dental abnormalities in patients with acromegaly.

Update in obstructive sleep apnea syndrome in children.

PubMed

Balbani, Aracy P S; Weber, Silke A T; Montovani, Jair C

2005-01-01

The prevalence of OSAS in children is 0.7-3%, with peak incidence in pre-schoolers. It is characterised by partial or complete upper airway obstruction during sleep, causing intermittent hypoxia. Both anatomical (severe nasal obstruction, craniofacial anomalies, hypertrophy of the pharyngeal lymphoid tissue, laryngeal anomalies, etc.) and functional factors (neuromuscular diseases) predispose to OSAS during childhood. The main cause of OSAS in children in adenotonsillar hypertrophy. The most common clinical manifestations of OSAS are: nocturnal snoring, respiratory pauses, restless sleep and mouth breathing. Nocturnal pulse oximetry, nocturnal noise audio/videotape recording and nap polysomnography are useful tools for screening suspected cases of OSAS in children, and the gold-standard for diagnosis is overnight polysomnography in the sleep laboratory. On the contrary of SAOS adults, children usually present: less arousals associated to apnea events, more numerous apneas/hypopneas during REM sleep, and more significant oxyhemoglobin desaturation even in short apneas. The treatment of OSAS may be surgical (adenotonsillectomy, craniofacial abnormalities correction, tracheostomy) or clinical (sleep hygiene, continuous positive airway pressure--CPAP).

Roberts-SC phocomelia syndrome.

PubMed

Maheshwari, A; Kumar, P; Dutta, S; Narang, A

2001-06-01

A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniofacial anomalies, microbrachycephaly, phocomelia in the upper limbs and renal cysts visible on ultrasound. He died of recurrent apneas. The autopsy showed left sided multicystic dysplastic kidney and absence of one testis. Cytogenetic studies did not reveal any abnormality. The phenotypic features match those described in the Roberts-SC phocomelia syndrome. A literature review revealed that 50% of these patients have chromosomal defects and antenatal detection is possible on ultrasound and by chromosome analysis of the amniocytes.

[Cryptorchidism with didymo-epididymal dissociation and Robinow's syndrome: 2 case reports].

PubMed

Fabbro, M A; D'Agostino, S; Costa, L; Musi, L; Cappellari, F

1997-01-01

Two brothers of normal not consanguineous parents, with bilateral intrabdominal cryptorchidism, were admitted to our Institution. Both children had short stature, limb and hand malformations and craniofacial patterns of Robinow syndrome. During the orchidopexy, bilateral epididymal and vasal abnormalities were found in both of them. This anomaly associated with Robinow syndrome has never been reported before. These two cases provides the Authors with the opportunity of reviewing clinical features, genetics and radiological patterns of this rare syndrome.

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

PubMed

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

2017-02-01

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

Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

PubMed Central

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

2008-01-01

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

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

PubMed Central

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

2013-01-01

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

Craniofacial trauma as a clinical marker of seizures in a baboon colony.

PubMed

Szabó, C Akos; Knape, Koyle D; Leland, M Michelle; Bauer, Cassondra; Williams, Jeff T

2014-04-01

Baboons provide a natural model of epilepsy. However, spontaneous seizures are usually sporadic, brief, and may not be observed. We hypothesized that various types of craniofacial trauma (CFT) may serve as reliable markers for epilepsy. We evaluated the type, demographics, and clinical significance of CFT in a large baboon colony. CFT was categorized according to somatotopic location, propensity to recur, and association with witnessed seizures or abnormal EEG findings. We divided the baboons with CFT into 2 groups: those with known histories of seizures (CFT+Sz, n = 176) and those without seizure histories (CFTonly; n = 515). In CFT+Sz baboons, the 568 injuries identified included periorbital (57%), scalp (27%), muzzle (12%), and facial (4%) injuries; multiple somatotopic locations or body parts were affected in 21 baboons. The most common CFT injuries associated with seizures were periorbital and scalp lesions (43% for each region). Compared with those in CFTonly animals, EEG abnormalities, including interictal epileptic discharges (IED) and photosensitivity were more prevalent in the CFT+Sz group, particularly among baboons with periorbital or scalp injuries. Compared with CFT+Sz animals, CFTonly baboons tended to have later onset and less frequent recurrence of CFT but higher prevalence of muzzle and tooth injuries. IED and photosensitivity were less prevalent in the CFTonly than the CFT+Sz group, with periorbital injuries carrying the highest and muzzle injuries the lowest association with IED or photosensitivity in both groups. Therefore, CFT in general and periorbital injuries in particular may be markers for seizures in baboons.

Craniofacial Trauma as a Clinical Marker of Seizures in a Baboon Colony

PubMed Central

Szabó, C Ákos; Knape, Koyle D; Leland, M Michelle; Bauer, Cassondra; Williams, Jeff T

2014-01-01

Baboons provide a natural model of epilepsy. However, spontaneous seizures are usually sporadic, brief, and may not be observed. We hypothesized that various types of craniofacial trauma (CFT) may serve as reliable markers for epilepsy. We evaluated the type, demographics, and clinical significance of CFT in a large baboon colony. CFT was categorized according to somatotopic location, propensity to recur, and association with witnessed seizures or abnormal EEG findings. We divided the baboons with CFT into 2 groups: those with known histories of seizures (CFT+Sz, n = 176) and those without seizure histories (CFTonly; n = 515). In CFT+Sz baboons, the 568 injuries identified included periorbital (57%), scalp (27%), muzzle (12%), and facial (4%) injuries; multiple somatotopic locations or body parts were affected in 21 baboons. The most common CFT injuries associated with seizures were periorbital and scalp lesions (43% for each region). Compared with those in CFTonly animals, EEG abnormalities, including interictal epileptic discharges (IED) and photosensitivity were more prevalent in the CFT+Sz group, particularly among baboons with periorbital or scalp injuries. Compared with CFT+Sz animals, CFTonly baboons tended to have later onset and less frequent recurrence of CFT but higher prevalence of muzzle and tooth injuries. IED and photosensitivity were less prevalent in the CFTonly than the CFT+Sz group, with periorbital injuries carrying the highest and muzzle injuries the lowest association with IED or photosensitivity in both groups. Therefore, CFT in general and periorbital injuries in particular may be markers for seizures in baboons. PMID:24674589

The importance of chromosome studies in Roberts syndrome/SC phocomelia and other cohesinopathies.

PubMed

Gerkes, Erica H; van der Kevie-Kersemaekers, Anne-Marie F; Yakin, Mariam; Smeets, Dominique F C M; van Ravenswaaij-Arts, Conny M A

2010-01-01

Roberts syndrome/SC phocomelia is a rare, autosomal recessive syndrome characterised by pre- and postnatal growth retardation, microcephaly, craniofacial anomalies, mental retardation, and tetraphocomelia in varying degrees of severity. The clinical diagnosis can be challenging in phenotypically mild cases. In the extremely mild case presented here, specific mitotic abnormalities were detected and proved to be very helpful, since Roberts syndrome/SC phocomelia could be diagnosed after finding premature centromere separation and somatic aneuploidy at routine karyotyping. We discuss these and other mitotic cytogenetic abnormalities that can be of significant diagnostic importance, but which will be missed if only array studies are performed. We also discuss the difference between premature centromere separation and premature (sister) chromatid separation. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

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

Maternal environment and craniofacial growth: geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice.

PubMed

Kesterke, Matthew J; Judd, Margaret A; Mooney, Mark P; Siegel, Michael I; Elsalanty, Mohammed; Howie, R Nicole; Weinberg, Seth M; Cray, James J

2018-07-01

An estimated 3% of US pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1000 pregnancies being complicated by overactive maternal thyroid levels. Excess thyroid hormones are linked to neurological impairment and excessive craniofacial variation, affecting both endochondral and intramembranous bone. Using a geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Canonical variate analysis utilized 16 unilateral mandibular landmarks obtained from 3D micro-computed tomography to assess shape changes between unexposed controls (n = 63) and exposed mice (n = 178). By evaluating shape changes in the mandible among three age groups (15, 20 and 25 days postnatal) and different dosage levels (low, medium and high), this study found that excess maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners. Group differences in overall shape were significant (P < 0.001), and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter the cranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development, as well as the medical implications of craniofacial growth and development. © 2018 Anatomical Society.

Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

PubMed

Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

2015-07-01

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general. © 2015 Anatomical Society.

Morphological and behavioral responses of zebrafish after 24 h of ketamine embryonic exposure

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

Félix, Luís M., E-mail: lfelix@utad.pt

Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24 h-LC{sub 50} was calculated from percent survival using probit analysis. Based on the 24 h-LC{sub 50} (94.4 mg L{sup −1}), embryos (2 hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24 h to ketamine concentrations of 50, 70 or 90 mg L{supmore » −1}. Developmental parameters were evaluated on the course of the experimental period, and anatomical abnormalities and locomotor deficits were analyzed at 144 hpf. Although the portion of ketamine transferred into the embryo was higher in the lowest exposed group (about 0.056 ± 0.020 pmol per embryo), the results showed that endpoints such as increased mortality, edema, heart rate alterations, malformation and abnormal growth rates were significantly affected. At 144 hpf, the developmental abnormalities included thoracic and trunk abnormalities in the groups exposed to 70 and 90 mg L{sup −1}. Defects in cartilage (alcian blue) and bone (calcein) elements also corroborated the craniofacial anomalies observed. A significant up-regulation of the development-related gene nog3 was detected by qRT-PCR at 8 hpf. Early exposure to ketamine also resulted in long-term behavioral changes, such as an increase in thigmotaxis and disruption of avoidance behavior at 144 hpf. Altogether, this study provides new evidence on the ketamine teratogenic potential, indicating a possible pharmacological impact of ketamine in aquatic environments. - Highlights: • 24 h exposure to ketamine increases mortality. • Morphological changes were observed after exposure. • Exposure to ketamine leads to severe craniofacial anomalies. • Developmental gene expression changes in response to ketamine. • Developmental ketamine exposure produces lasting behavioral changes.« less

Airway Management in a Patient with Wolf-Hirschhorn Syndrome.

PubMed

Gamble, John F; Kurian, Dinesh J; Udani, Andrea G; Greene, Nathaniel H

2016-01-01

We present a case of a 3-month-old female with Wolf-Hirschhorn syndrome (WHS) undergoing general anesthesia for laparoscopic gastrostomy tube placement with a focus on airway management. WHS is a rare 4p microdeletion syndrome resulting in multiple congenital abnormalities, including craniofacial deformities. Microcephaly, micrognathia, and glossoptosis are common features in WHS patients and risk factors for a pediatric airway that is potentially difficult to intubate. We discuss anesthesia strategies for airway preparation and management in a WHS patient requiring general anesthesia with endotracheal intubation.

Airway Management in a Patient with Wolf-Hirschhorn Syndrome

PubMed Central

Udani, Andrea G.

2016-01-01

We present a case of a 3-month-old female with Wolf-Hirschhorn syndrome (WHS) undergoing general anesthesia for laparoscopic gastrostomy tube placement with a focus on airway management. WHS is a rare 4p microdeletion syndrome resulting in multiple congenital abnormalities, including craniofacial deformities. Microcephaly, micrognathia, and glossoptosis are common features in WHS patients and risk factors for a pediatric airway that is potentially difficult to intubate. We discuss anesthesia strategies for airway preparation and management in a WHS patient requiring general anesthesia with endotracheal intubation. PMID:27752382

De novo frameshift mutation in fibroblast growth factor 8 in a male patient with gonadotropin deficiency.

PubMed

Suzuki, Erina; Yatsuga, Shuichi; Igarashi, Maki; Miyado, Mami; Nakabayashi, Kazuhiko; Hayashi, Keiko; Hata, Kenichirou; Umezawa, Akihiro; Yamada, Gen; Ogata, Tsutomu; Fukami, Maki

2014-01-01

Missense, nonsense, and splice mutations in the Fibroblast Growth Factor 8(FGF8) have recently been identified in patients with hypothalamo-pituitary dysfunction and craniofacial anomalies. Here, we report a male patient with a frameshift mutation in FGF8. The patient exhibited micropenis, craniofacial anomalies, and ventricular septal defect at birth. Clinical evaluation at 16 years and 8 months of age revealed delayed puberty, hyposmia, borderline mental retardation, and mild hearing difficulty. Endocrine findings included gonadotropin deficiency and primary hypothyroidism. Molecular analysis identified a de novo heterozygous p.S192fsX204 mutation in the last exon of FGF8. RT-PCR analysis of normal human tissues detected FGF8 expression in the genital skin, and whole-mount in situ hybridization analysis of mouse embryos revealed Fgf8 expression in the anlage of the penis. The results indicate that frameshift mutations in FGF8 account for a part of the etiology of hypothalamo-pituitary dysfunction. Micropenis in patients with FGF8 abnormalities appears to be caused by gonadotropin deficiency and defective outgrowth of the anlage of the penis.

WNT5A Mutations in Patients with Autosomal Dominant Robinow Syndrome

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-01-01

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

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

PubMed

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

2013-01-01

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

Cleft and Craniofacial Care During Military Pediatric Plastic Surgery Humanitarian Missions.

PubMed

Madsen, Christopher; Lough, Denver; Lim, Alan; Harshbarger, Raymond J; Kumar, Anand R

2015-06-01

Military pediatric plastic surgery humanitarian missions in the Western Hemisphere have been initiated and developed since the early 1990 s using the Medical Readiness Education and Training Exercise (MEDRETE) concept. Despite its initial training mission status, the MEDRETE has developed into the most common and advanced low level medical mission platform currently in use. The objective of this study is to report cleft- and craniofacial-related patient outcomes after initiation and evolution of a standardized treatment protocol highlighting lessons learned which apply to civilian plastic surgery missions. A review of the MEDRETE database for pediatric plastic surgery/cleft and craniofacial missions to the Dominican Republic from 2005 to 2009 was performed. A multidisciplinary team including a craniofacial surgeon evaluated all patients with a cleft/craniofacial and/or pediatric plastic condition. A standardized mission time line included predeployment site survey and predeployment checklist, operational brief, and postdeployment after action report. Deployment data collection, remote patient follow-up, and coordination with larger land/amphibious military operations was used to increase patient follow-up data. Data collected included sex, age, diagnosis, date and type of procedure, surgical outcomes including speech scores, surgical morbidity, and mortality. Five hundred ninety-four patients with cleft/craniofacial abnormalities were screened by a multidisciplinary team including craniofacial surgeons over 4 years. Two hundred twenty-three patients underwent 330 surgical procedures (cleft lip, 53; cleft palate, 73; revision cleft lip/nose, 73; rhinoplasty, 15; speech surgery, 24; orthognathic/distraction, 21; general pediatric plastic surgery, 58; fistula repair, 12). Average follow-up was 30 months (range, 1-60). The complication rate was 6% (n = 13) (palate fistula, lip revision, dental/alveolar loss, revision speech surgery rate). The average pre-surgical (Pittsburgh Weighted Speech Score) speech score was 12 (range, 6-24). The average postsurgical speech score was 6 (range, 0-21). Average hospital stay was 3 days for cleft surgery. There were no major complications or mortality, 1 reoperation for bleeding or infection, and 12 patients required secondary operations for palatal fistula, unsatisfactory aesthetic result, malocclusion, or velopharygeal dysfunction. Military pediatric plastic surgery humanitarian missions can be executed with similar home institution results after the initiation and evolution of a standardized approach to humanitarian missions. The incorporation of a dedicated logistics support unit, a dedicated operational specialist (senior noncommissioned officer), a speech language pathologist, remote internet follow up, an liaison officer (host nation liaison physician participation), host nation surgical resident participation, and support from the embassy, Military Advisory Attachment Group, and United States Aid and International Development facilitated patient accurate patient evaluation and posttreatment follow-up. Movement of the mission site from a remote more austere environment to a centralized better equipped facility with host nation support to transport patients to the site facilitated improved patient safety and outcomes despite increasing the complexity of surgery performed.

SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations.

PubMed

Zarate, Yuri A; Fish, Jennifer L

2017-02-01

The SATB2-associated syndrome is a recently described syndrome characterized by developmental delay/intellectual disability with absent or limited speech development, craniofacial abnormalities, behavioral problems, dysmorphic features, and palatal and dental abnormalities. Alterations of the SATB2 gene can result from a variety of different mechanisms that include contiguous deletions, intragenic deletions and duplications, translocations with secondary gene disruption, and point mutations. The multisystemic nature of this syndrome demands a multisystemic approach and we propose evaluation and management guidelines. The SATB2-associated syndrome registry has now been started and that will allow gathering further clinical information and refining the provided surveillance recommendations. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

PubMed

Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R; Matsushita, Mark; Raskind, Wendy H

2008-07-15

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. 2008 Wiley-Liss, Inc.

Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation.

PubMed

Schüle, Birgitt; Oviedo, Angelica; Johnston, Kathreen; Pai, Shashidhar; Francke, Uta

2005-12-01

The rare, autosomal recessive Roberts syndrome (RBS) is characterized by tetraphocomelia, profound growth deficiency of prenatal onset, craniofacial anomalies, microcephaly, and mental deficiency. SC phocomelia (SC) has a milder phenotype, with a lesser degree of limb reduction and with survival to adulthood. Since heterochromatin repulsion (HR) is characteristic for both disorders and is not complemented in somatic-cell hybrids, it has been hypothesized that the disorders are allelic. Recently, mutations in ESCO2 (establishment of cohesion 1 homolog 2) on 8p21.1 have been reported in RBS. To determine whether ESCO2 mutations are also responsible for SC, we studied three families with SC and two families in which variable degrees of limb and craniofacial abnormalities, detected by fetal ultrasound, led to pregnancy terminations. All cases were positive for HR. We identified seven novel mutations in exons 3-8 of ESCO2. In two families, affected individuals were homozygous--for a 5-nucleotide deletion in one family and a splice-site mutation in the other. In three nonconsanguineous families, probands were compound heterozygous for a single-nucleotide insertion or deletion, a nonsense mutation, or a splice-site mutation. Abnormal splice products were characterized at the RNA level. Since only protein-truncating mutations were identified, regardless of clinical severity, we conclude that genotype does not predict phenotype. Having established that RBS and SC are caused by mutations in the same gene, we delineated the clinical phenotype of the tetraphocomelia spectrum that is associated with HR and ESCO2 mutations and differentiated it from other types of phocomelia that are negative for HR.

[Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China].

PubMed

Zhang, Qin; Bai, Bao-Ling; Liu, Xiao-Zhen; Miao, Chun-Yue; Li, Hui-Li

2014-08-01

To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.

The Effects of Tissue-Nonspecific Alkaline Phosphatase Gene Therapy on Craniosynostosis and Craniofacial Morphology in the FGFR2C342Y/+ Mouse Model of Crouzon Craniosynostosis

PubMed Central

Wang, E; Nam, HK; Liu, J; Hatch, NE

2015-01-01

Objectives Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-nonspecific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Material & Methods Neonatal Crouzon (FGFRC342Y/+) and wild type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at four weeks post-natal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology was assessed by micro-computed tomography. Results Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphologic analysis revealed craniofacial form differences for inferior surface (p=.023) and cranial height (p=.014) regions between TNAP lentivirus injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=.068). Conclusion These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery. PMID:25865549

A low-cost method of craniofacial distraction osteogenesis.

PubMed

Greyvensteyn, Gerhardus A; Madaree, Anil

2016-03-01

Distraction osteogenesis is an effective treatment modality for the correction of craniofacial deformities. The cost of these devices is significant and may preclude routine use of these distractors in developing countries. Hence, distraction osteogenesis was performed using medical equipment that was readily available in any hospital at minimal cost. From 2008 to 2013, a retrospective study was performed on infants and neonates who underwent primary distraction for craniofacial abnormalities. Midface or mandibular distraction was performed because of respiratory impairment and/or globe exposure. The apparatus used included Steinmann pins, stainless steel wires, attachment bolts, orthopaedic pulleys, string and intravenous bags for weights. For midface distraction, a transzygomatic pin was inserted, and a transmandibular pin or a cerclage wire was inserted into the mandible through the symphysis or body of the mandible and connected to the pulley system. Distraction osteogenesis was performed on five patients - three mandibular distractions (Pierre Robin sequence) and two transfacial distractions (Apert syndrome/Pfeiffer syndrome type III). The mean age, duration of distraction and duration of consolidation at the time of distraction was 60.5 days, 18.6 days and 16.4 days, respectively. The mean length of distraction achieved was 12 mm. Common complications observed were pin loosening, pressure necrosis of the skin and uneven pull. A major disadvantage was the longer hospital stay required. The African method of distraction is effective, easy and cost effective and could be used in third-world hospitals where surgical expertise or expensive distraction sets are not freely available. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Repair of Frontoethmoidal Encephalocele in the Philippines: An Account of 30 Cases Between 2008-2013.

PubMed

Marshall, Amanda-Lynn; Setty, Pradeep; Hnatiuk, Mark; Pieper, Daniel R

2017-07-01

Frontoethmoidal encephalocele is a congenital abnormality of the anterior skull base involving herniation of cranial contents through a midline skull defect. Patency of the foramen cecum, along with other multifactorial variables, contributes to the development of frontoethmoidal encephaloceles. Because of limited resources, financial constraints, and lack of surgical expertise, repair of frontoethmoidal encephaloceles is limited in developing countries. Between 2008 and 2013 an interdisciplinary team composed of neurosurgeons, craniofacial surgeons, otolaryngologists, plastic surgeons, and nursing personnel, conducted surgical mission trips to Davao City in Mindanao, Philippines. All patients underwent a combined extracranial/intracranial surgical approach, performed in tandem by a neurosurgeon and a craniofacial surgeon, to detach and remove the encephalocele. This procedure was followed by reconstruction of the craniofacial defects. A total of 30 cases of frontoethmoidal encephalocele were repaired between 2008 and 2013 (20 male; 10 female). The average age at operation was 8.7 years, with 7 patients older than 17 years. Of the 3 subtypes, the following breakdown was observed in patients: 18 nasoethmoidal; 9 nasofrontal; and 3 naso-orbital. Several patients showed concurrent including enlarged ventricles, arachnoid cysts (both unilateral and bilateral), and gliotic changes, as well as orbit and bulbus oculi (globe) deformities. There were no operative-associated mortalities or neurologic deficits, infections, or hydrocephalus on follow-up during subsequent trips. Despite the limitations of performing advanced surgery in a developing country, the combined interdisciplinary surgical approach has offered effective treatment to improve physical appearance and psychological well-being in afflicted patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Swyer-James syndrome associated with Noonan syndrome: report of a case.

PubMed

Lin, Y M; Huang, W L; Hwang, J J; Ko, Y L; Lien, W P

1995-12-01

A 28-year-old man with Noonan syndrome associated with unilateral hyperlucent lung is reported. He had the typical craniofacial appearance and short stature of Noonan syndrome; he had mild mental retardation, atrophic testis, mild funnel chest and kyphosis. cardiovascular abnormalities included asymmetric hypertrophic cardiomyopathy and a significantly different caliber of the left and right pulmonary arteries. The unilateral hyperlucent lung was shown to result from acquired nondestructive emphysema caused by nonvalvular obstruction of the bronchi (Swyer-James syndrome or Macleod's syndrome). To the authors' knowledge, this is the first reported case of Noonan syndrome associated with Swyer-James syndrome.

Axenfeld-Rieger syndrome (ARS): A review and case report.

PubMed

Waldron, Jennie M; McNamara, Clare; Hewson, Antonia R; McNamara, C M

2010-01-01

Axenfeld-Rieger syndrome (ARS) is a rare, autosomal dominant condition characterized by ocular, craniofacial, dental, and periumbilical abnormalities. Relatively little information exists on this syndrome within the dental literature despite the fact that midface hypoplasia and maxillary hypodontia are classical presenting features of this syndrome. This is a case report of a 7-year-old Caucasian female with ARS who presented with significant ocular and dental anomalies. She was also found to have osteopenia. Her dental condition is described, her immediate treatment is shown, and her long-term treatment needs are discussed. ©2010 Special Care Dentistry Association and Wiley Periodicals, Inc.

Holoprosencephaly: from Homer to Hedgehog.

PubMed

Ming, J E; Muenke, M

1998-03-01

Holoprosencephaly (HPE), a common developmental defect affecting the forebrain and face, is etiologically heterogeneous and exhibits wide phenotypic variation. Graded degrees of severity of the brain malformation are also reflected in the highly variable craniofacial malformations associated with HPE. In addition, individuals with microforms of HPE, who usually have normal cognition and normal brain imaging, are at risk for having children with HPE. Some obligate carriers for HPE may not have any phenotypic abnormalities. Recurrent chromosomal rearrangements in individuals with HPE suggest loci containing genes important for brain development, and abnormalities in these genes may result in HPE. Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in humans. Proper function of SHH depends on cholesterol modification. Other candidate genes that may be involved in HPE include components of the SHH pathway, elements involved in cholesterol metabolism, and genes expressed in the developing forebrain.

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

PubMed

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

2016-07-08

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

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

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

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

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

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

PubMed Central

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

2013-01-01

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

Elucidation of possible molecular mechanisms underlying the estrogen-induced disruption of cartilage development in zebrafish larvae.

PubMed

He, Hanliang; Wang, Chunqing; Tang, Qifeng; Yang, Fan; Xu, Youjia

2018-06-01

Estrogen can affect the cartilage development of zebrafish; however, the mechanism underlying its effects is not completely understood. Four-day-old zebrafish larvae were treated with 0.8 μM estrogen, the 5 days post fertilization (dpf) zebrafish larvae did not demonstrate obvious abnormalities during development; however, the 6 dpf and 7 dpf larvae exhibited abnormal craniofacial bone development along with craniofacial bone degradation. RNA deep sequencing was performed to elucidate the mechanism involved. Gene Ontology functional and KEGG pathway enrichment analysis of differentially expressed genes (DEGs) showed that the extracellular matrix (ECM), extracellular region, ECM-interaction receptor, focal adhesion, cell cycle, apoptosis, and bone-related signaling pathways were disrupted. In these signaling pathways, the expressions of key genes, such as collagen encoded (col19a1a, col7a1, col7al, col18a1, and col9a3), MAPK signaling pathway (fgf19, fgf6a), TGF-beta signaling pathway (tgfbr1), and cell cycle (cdnk1a) genes were altered. The qRT-PCR results showed that after treatment with 0.8 μM 17-β estradiol (E2), col19a1a, col7a1, col7al, col18a1, col9a3, fgf6a, cdkn1a were downregulated, and fgf19, tgfr1 were upregulated, which were consistent with deep sequencing analysis. Therefore, the effect of estrogen on cartilage development might occur via multiple mechanisms. The study results demonstrate the mechanism underlying the effect of estrogen on cartilage development. Copyright © 2018 Elsevier B.V. All rights reserved.

Inactivating Mutations in ESCO2 Cause SC Phocomelia and Roberts Syndrome: No Phenotype-Genotype Correlation

PubMed Central

Schüle, Birgitt; Oviedo, Angelica; Johnston, Kathreen; Pai, Shashidhar; Francke, Uta

2005-01-01

The rare, autosomal recessive Roberts syndrome (RBS) is characterized by tetraphocomelia, profound growth deficiency of prenatal onset, craniofacial anomalies, microcephaly, and mental deficiency. SC phocomelia (SC) has a milder phenotype, with a lesser degree of limb reduction and with survival to adulthood. Since heterochromatin repulsion (HR) is characteristic for both disorders and is not complemented in somatic-cell hybrids, it has been hypothesized that the disorders are allelic. Recently, mutations in ESCO2 (establishment of cohesion 1 homolog 2) on 8p21.1 have been reported in RBS. To determine whether ESCO2 mutations are also responsible for SC, we studied three families with SC and two families in which variable degrees of limb and craniofacial abnormalities, detected by fetal ultrasound, led to pregnancy terminations. All cases were positive for HR. We identified seven novel mutations in exons 3–8 of ESCO2. In two families, affected individuals were homozygous—for a 5-nucleotide deletion in one family and a splice-site mutation in the other. In three nonconsanguineous families, probands were compound heterozygous for a single-nucleotide insertion or deletion, a nonsense mutation, or a splice-site mutation. Abnormal splice products were characterized at the RNA level. Since only protein-truncating mutations were identified, regardless of clinical severity, we conclude that genotype does not predict phenotype. Having established that RBS and SC are caused by mutations in the same gene, we delineated the clinical phenotype of the tetraphocomelia spectrum that is associated with HR and ESCO2 mutations and differentiated it from other types of phocomelia that are negative for HR. PMID:16380922

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

Craniofacial imaging informatics and technology development.

PubMed

Vannier, M W

2003-01-01

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

Ritscher-Schinzel cranio-cerebello-cardiac (3C) syndrome: report of four new cases and review.

PubMed

Leonardi, M L; Pai, G S; Wilkes, B; Lebel, R R

2001-08-15

Ritscher-Schinzel syndrome, also known as the 3C syndrome, is a rare, autosomal recessive syndrome characterized by craniofacial, cerebellar, and cardiac anomalies. Cardiac manifestations include ventricular septal defect, atrial septal defect, tetralogy of Fallot, double outlet right ventricle, hypoplastic left heart, aortic stenosis, pulmonic stenosis and other valvular anomalies. Central nervous system anomalies include Dandy-Walker malformation, cerebellar vermis hypoplasia and enlargement of the cisterna magna. Craniofacial abnormalities seen are cleft palate, ocular coloboma, prominent occiput, low-set ears, hypertelorism, down-slanting palpebral fissures, depressed nasal bridge and micrognathia. Dandy-Walker malformation, posterior fossa cyst, hydrocephalus and congenital heart defect are common malformations that may occur in isolation or as a part of many syndromes. Accurate genetic diagnosis and counseling require detailed analysis of the external as well as the internal anatomy and knowledge of the relative frequencies of various malformations in syndromes that may have overlapping clinical signs. We have had the opportunity recently to study four cases of the Ritscher-Schinzel syndrome. A review of all reported cases is presented and an attempt made to define the minimum diagnostic criteria for the Ritscher-Schinzel syndrome. Of the nine craniofacial anomalies commonly reported as a part of the Ritscher-Schinzel syndrome, we consider two i.e., cleft palate and ocular coloboma, to be readily and objectively ascertainable. The other seven craniofacial traits, however, are somewhat subjective, require expert interpretation and are sometimes difficult to ascertain in a newborn or stillborn fetus. These are prominent forehead, prominent occiput, hypertelorism, down-slanting palpebral fissures, low-set ears, depressed nasal bridge and micrognathia. At least four of these were present in all cases that had a secure diagnosis of the Ritscher-Schinzel syndrome. Thus, the criteria we propose to establish the diagnosis of the Ritscher-Schinzel syndrome in a chromosomally normal sporadic case are the presence of cardiac malformation other than isolated patent ductus arteriosus, cerebellar malformation, and cleft palate or ocular coloboma or four of the following seven findings: prominent forehead, prominent occiput, hypertelorism, down-slanting palpebral fissures, low-set ears, depressed nasal bridge, and micrognathia. Copyright 2001 Wiley-Liss, Inc.

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

PubMed Central

Chen, Yucong; Deng, Qingqiong; Duan, Fuqing

2017-01-01

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

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

PubMed

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

2017-01-01

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

The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

PubMed

Wang, E; Nam, H K; Liu, J; Hatch, N E

2015-04-01

Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A LINE-1 Insertion in DLX6 Is Responsible for Cleft Palate and Mandibular Abnormalities in a Canine Model of Pierre Robin Sequence

PubMed Central

Wolf, Zena T.; Leslie, Elizabeth J.; Arzi, Boaz; Jayashankar, Kartika; Karmi, Nili; Jia, Zhonglin; Rowland, Douglas J.; Young, Amy; Safra, Noa; Sliskovic, Saundra; Murray, Jeffrey C.; Wade, Claire M.; Bannasch, Danika L.

2014-01-01

Cleft palate (CP) is one of the most commonly occurring craniofacial birth defects in humans. In order to study cleft palate in a naturally occurring model system, we utilized the Nova Scotia Duck Tolling Retriever (NSDTR) dog breed. Micro-computed tomography analysis of CP NSDTR craniofacial structures revealed that these dogs exhibit defects similar to those observed in a recognizable subgroup of humans with CP: Pierre Robin Sequence (PRS). We refer to this phenotype in NSDTRs as CP1. Individuals with PRS have a triad of birth defects: shortened mandible, posteriorly placed tongue, and cleft palate. A genome-wide association study in 14 CP NSDTRs and 72 unaffected NSDTRs identified a significantly associated region on canine chromosome 14 (24.2 Mb–29.3 Mb; praw = 4.64×10−15). Sequencing of two regional candidate homeobox genes in NSDTRs, distal-less homeobox 5 (DLX5) and distal-less homeobox 6 (DLX6), identified a 2.1 kb LINE-1 insertion within DLX6 in CP1 NSDTRs. The LINE-1 insertion is predicted to insert a premature stop codon within the homeodomain of DLX6. This prompted the sequencing of DLX5 and DLX6 in a human cohort with CP, where a missense mutation within the highly conserved DLX5 homeobox of a patient with PRS was identified. This suggests the involvement of DLX5 in the development of PRS. These results demonstrate the power of the canine animal model as a genetically tractable approach to understanding naturally occurring craniofacial birth defects in humans. PMID:24699068

Reconstruction of late craniofacial deformities after irradiation of the head and face during childhood

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

Cohen, S.R.; Bartlett, S.P.; Whitaker, L.A.

1990-08-01

Little is known about the results of surgical management of late craniofacial abnormalities arising after irradiation of the head and face for treatment of childhood cancers. The clinical records of 10 children (4 males and 6 females) who received 4500 to 6500 rads (mean 5160 rads) of craniofacial radiation between birth and 8 years of age (mean 5 years) and who subsequently had reconstructive surgery were reviewed. Six of the 10 patients received orbital radiation, 3 received maxillary-midfacial radiation, and 1 patient underwent radiation to the frontal bone. Histologic tumor types included retinoblastoma (4), rhabdomyosarcoma (3), Ewing's sarcoma (2), andmore » neurofibrosarcoma (1). In addition to radiation, 7 of the 10 patients underwent surgical resection or debulking of their tumors and 6 received adjuvant chemotherapy. All patients presented from 4 to 20 years after treatment (mean 10 years) with varying, but severe degrees of soft-tissue and bony hypoplasia of the irradiated territories. Onlay bone grafting with soft-tissue reconstruction by a combination of local pedicle flaps and dermal-fat grafts was initially performed in 9 patients, and an occipitoparietal bone-flap switch procedure was done in 1 patient. Late follow-up ranged from 11 months to 7.5 years (mean 34 months). A total of 8 secondary procedures were necessary in 4 of the 10 patients (40 percent). Of these 4 patients, major revisions were performed in 3 and minor adjustments in 1. In addition, 2 patients in whom secondary procedures had not been done would benefit from further reconstruction. Therapy for cancer of the head and face during childhood has profound and ongoing effects on the growth of soft tissue and bone.« less

Clinical and experimental evidence suggest a link between KIF7 and C5orf42-related ciliopathies through Sonic Hedgehog signaling.

PubMed

Asadollahi, Reza; Strauss, Justin E; Zenker, Martin; Beuing, Oliver; Edvardson, Simon; Elpeleg, Orly; Strom, Tim M; Joset, Pascal; Niedrist, Dunja; Otte, Christine; Oneda, Beatrice; Boonsawat, Paranchai; Azzarello-Burri, Silvia; Bartholdi, Deborah; Papik, Michael; Zweier, Markus; Haas, Cordula; Ekici, Arif B; Baumer, Alessandra; Boltshauser, Eugen; Steindl, Katharina; Nothnagel, Michael; Schinzel, Albert; Stoeckli, Esther T; Rauch, Anita

2018-02-01

Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7 defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies. We found (likely) pathogenic variants of KIF7 in 5 out of 9 families, including the original ACLS patients, and delineated 1000 to 4000-year-old Swiss founder alleles. Three of the remaining families had (likely) pathogenic variants in the JBTS gene C5orf42, and one patient had a novel de novo frameshift variant in SHH known to cause autosomal dominant holoprosencephaly. In accordance with the patients' craniofacial anomalies, we showed facial midline widening after silencing of C5orf42 in chicken embryos. We further supported the link between KIF7, SHH, and C5orf42 by demonstrating abnormal primary cilia and diminished response to a SHH agonist in fibroblasts of C5orf42-mutated patients, as well as axonal pathfinding errors in C5orf42-silenced chicken embryos similar to those observed after perturbation of Shh signaling. Our findings, therefore, suggest that beside the neurodevelopmental features, macrocephaly and facial widening are likely more general signs of disturbed SHH signaling. Nevertheless, long-term follow-up revealed that C5orf42-mutated patients showed catch-up development and fainting of facial features contrary to KIF7-mutated patients.

Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial defects in zebrafish.

PubMed

Signore, Iskra A; Jerez, Carolina; Figueroa, Diego; Suazo, José; Marcelain, Katherine; Cerda, Oscar; Colombo Flores, Alicia

2016-10-01

Orofacial clefts (OFCs) are common birth defects, which include a range of disorders with a complex etiology affecting formation of craniofacial structures. Some forms of syndromic OFCs are produced by defects in the cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether defects of HMGCR function would produce orofacial malformation similar to those found in disorders of cholesterol synthesis. We used zebrafish hmgcrb mutants and HMGCR inhibition assay using atorvastatin during early and late stages of orofacial morphogenesis in zebrafish. To describe craniofacial phenotypes, we stained cartilage and bone and performed in situ hybridization using known craniofacial markers. Also, we visualized neural crest cell migration in a transgenic fish. Our results showed that mutants displayed loss of cartilage and diminished orofacial outgrowth, and in some cases palatal cleft. Late treatments with statin show a similar phenotype. Affected-siblings displayed a moderate phenotype, whereas early-treated embryos had a minor cleft. We found reduced expression of the downstream component of Sonic Hedgehog-signaling gli1 in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late atorvastatin-treated embryos. Our results suggest that HMGCR loss-of-function primarily affects postmigratory cranial neural crest cells through abnormal Sonic Hedgehog signaling, probably induced by reduction in metabolites of the cholesterol pathway. Malformation severity correlates with the grade of HMGCR inhibition, developmental stage of its disruption, and probably with availability of maternal lipids. Together, our results might help to understand the spectrum of orofacial phenotypes found in cholesterol synthesis disorders. Birth Defects Research (Part A) 106:814-830, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Potential Novel Mechanism for Axenfeld-Rieger Syndrome: Deletion of a Distant Region Containing Regulatory Elements of PITX2

PubMed Central

Volkmann, Bethany A.; Zinkevich, Natalya S.; Mustonen, Aki; Schilter, Kala F.; Bosenko, Dmitry V.; Reis, Linda M.; Broeckel, Ulrich; Link, Brian A.

2011-01-01

Purpose. Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Methods. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Results. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. Conclusions. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion. PMID:20881290

Bilateral meningoencephaloceles with cerebrospinal fluid rhinorrhea after facial advancement in the Crouzon syndrome.

PubMed

Panuganti, Bharat A; Leach, Matthew; Antisdel, Jastin

2015-01-01

Cerebrospinal fluid (CSF) rhinorrhea and encephaloceles are rare complications of craniofacial advancement procedures performed in patients with craniofacial dysostoses (CD) to address the ramifications of their midface hypoplasia including obstructed nasal airway, exorbitism, and impaired mastication. Surgical repair of this CSF rhinorrhea is complicated by occult elevations in intracranial pressure (ICP), potentially necessitating open, transcranial repair. We report the first case in otolaryngology literature of a patient with Crouzon syndrome with late CSF rhinorrhea and encephalocele formation after previous LeFort III facial advancement surgery. Describe the case of a patient with Crouzon syndrome who presented with CSF rhinorrhea and encephaloceles as complications of Le Fort III facial advancement surgery. Review the literature pertaining to the incidence and management of post-operative CSF rhinorrhea and encephaloceles. Analyze issues related to repair of these complications, including occult elevations in ICP, the utility of perioperative CSF shunts, and the importance of considering alternative repair schemes to the traditional endonasal, endoscopic approach. Review of the literature describing CSF rhinorrhea and encephalocele formation following facial advancement in CD, focusing on management strategies. CSF rhinorrhea and encephalocele formation are rare complications of craniofacial advancement procedures. Occult elevations in ICP complicate the prospect of permanent surgical repair, potentially necessitating transcranial repair and the use of CSF shunts. Though no consensus exists regarding the utility of perioperative CSF drains, strong associations exist between elevated ICP and failed surgical repair. Additionally, the anatomic changes in the frontal and ethmoid sinuses after facial advancement present a challenge to endoscopic repair. Otolaryngologists should be aware of the possibility of occult elevations in ICP and sinonasal anatomic abnormalities when repairing CSF rhinorrhea in patients with CD. Clinicians should consider CSF shunt placement and carefully weigh the advantages of the transcranial approach versus endonasal, endoscopic techniques.

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

PubMed

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

2015-09-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

PubMed

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

2017-02-01

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

Hemifacial Spasm: A Neurosurgical Perspective

PubMed Central

Kong, Doo-Sik

2007-01-01

Hemifacial spasm (HFS) is characterized by tonic clonic contractions of the muscles innervated by the ipsilateral facial nerve. Compression of the facial nerve by an ectatic vessel is widely recognized as the most common underlying etiology. HFS needs to be differentiated from other causes of facial spasms, such as facial tic, ocular myokymia, and blepharospasm. To understand the overall craniofacial abnormalities and to perform the optimal surgical procedures for HFS, we are to review the prevalence, pathophysiology, differential diagnosis, details of each treatment modality, usefulness of brainstem auditory evoked potentials monitoring, debates on the facial EMG, clinical course, and complications from the literature published from 1995 to the present time. PMID:19096569

Timetable for oral prevention in childhood--developing dentition and oral habits: a current opinion.

PubMed

Majorana, Alessandra; Bardellini, Elena; Amadori, Francesca; Conti, Giulio; Polimeni, Antonella

2015-01-01

As most of the etiologic factors of malocclusion are of genetic origin and thus cannot be prevented, environmental causative factors have become the focus for correction. Early interception of oral habits may be an important step in order to prevent occlusal disturbances in children. The identification of an abnormal habit and the assessment of its potential immediate and long-term effects on the dentition and potentially on the craniofacial complex should be made at an early stage. This paper focuses on the most common oral habits influencing dentofacial growth in childhood and management of these habits in the developing dentition.

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

PubMed

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

2011-01-01

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

Meis2 is essential for cranial and cardiac neural crest development.

PubMed

Machon, Ondrej; Masek, Jan; Machonova, Olga; Krauss, Stefan; Kozmik, Zbynek

2015-11-06

TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Disturbances of dental development distinguish patients with oligodontia-ectodermal dysplasia from isolated oligodontia.

PubMed

Dhamo, B; Kuijpers, M A R; Balk-Leurs, I; Boxum, C; Wolvius, E B; Ongkosuwito, E M

2018-02-01

To investigate phenotypic differences in dental development between isolated oligodontia and oligodontia-ectodermal dysplasia (ED). A total of 129 patients diagnosed with isolated oligodontia and 22 patients with oligodontia as part of ED were eligible. The phenotype of dental development was assessed for the frequency of missing a certain tooth, dental age, development of each tooth present, abnormal size and abnormal shape of teeth. The data were analysed building linear, ordinal and logistic regression models. Compared to patients with isolated oligodontia, patients with oligodontia-ED missed more frequently central incisors and second molars in both jaws, and lateral incisors in the mandible (P < .05). Oligodontia-ED was associated with delayed development of the permanent dentition (β = -0.10; 95% CI: -0.17, -0.03). Specifically, the maxillary teeth: right central incisor, right lateral incisor, right second premolar and left second premolar were delayed approximately from 2 to 4 developmental stages. In addition, the left mandibular second premolar was 3 developmental stages delayed. Abnormal shape of teeth was 7 times more evident in patients with oligodontia-ED compared to patients with isolated oligodontia (OR = 6.54; 95% CI: 2.34, 18.28). The abnormal size of teeth was not a distinctive characteristic for oligodontia-ED. Oligodontia-ED distinguishes from isolated oligodontia by more disturbances in dental development. The abnormal shape of incisors and canines in a patient with oligodontia can raise suspicions for accompanying ectodermal abnormalities. © 2017 The Authors. Orthodontics & Craniofacial Research Published by John Wiley & Sons Ltd.

Craniometaphyseal dysplasia with obvious biochemical abnormality and rickets-like features.

PubMed

Wu, Bo; Jiang, Yan; Wang, Ou; Li, Mei; Xing, Xiao-Ping; Xia, Wei-Bo

2016-05-01

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long bones, and biochemical indexes were mostly normal. To further the understanding of the disease from a biochemical perspective, we reported a CMD case with obviously abnormal biochemical indexes. A 1-year-old boy was referred to our clinic. Biochemical test showed obviously increased alkaline phosphatase (ALP) and parathyroid hormone (PTH), mild hypocalcemia and hypophosphatemia. Moreover, significant elevated receptor activator of nuclear factor kappa-B ligand (RANKL) level, but normal β-C-terminal telopeptide of type I collagen (β-CTX) concentration were revealed. He was initially suspected of rickets, because the radiological examination also showed broadened epiphysis in his long bones. Supplementation with calcium and calcitriol alleviated biochemical abnormality. However, the patient gradually developed osteosclerosis which was inconformity with rickets. Considering that he was also presented with facial paralysis and nasal obstruction symptom, the diagnosis of craniometaphyseal dysplasia was suspected, and then was confirmed by the mutation analysis of ANKH of the proband and his family, which showed a de novo heterozygous mutation (C1124-1126delCCT) on exon 9. Our study revealed that obvious biochemical abnormality and rickets-like features might present as uncommon characteristics in CMD patients, and the calcium and calcitriol supplementation could alleviate biochemical abnormalities. Furthermore, although early osteoclast differentiation factor was excited in CMD patient, activity of osteoclast was still inert. Copyright © 2016. Published by Elsevier B.V.

Whole exome sequencing identifies a POLRID mutation segregating in a father and two daughters with findings of Klippel-Feil and Treacher Collins syndromes.

PubMed

Giampietro, Philip F; Armstrong, Linlea; Stoddard, Alex; Blank, Robert D; Livingston, Janet; Raggio, Cathy L; Rasmussen, Kristen; Pickart, Michael; Lorier, Rachel; Turner, Amy; Sund, Sarah; Sobrera, Nara; Neptune, Enid; Sweetser, David; Santiago-Cornier, Alberto; Broeckel, Ulrich

2015-01-01

We report on a father and his two daughters diagnosed with Klippel-Feil syndrome (KFS) but with craniofacial differences (zygomatic and mandibular hypoplasia and cleft palate) and external ear abnormalities suggestive of Treacher Collins syndrome (TCS). The diagnosis of KFS was favored, given that the neck anomalies were the predominant manifestations, and that the diagnosis predated later recognition of the association between spinal segmentation abnormalities and TCS. Genetic heterogeneity and the rarity of large families with KFS have limited the ability to identify mutations by traditional methods. Whole exome sequencing identified a nonsynonymous mutation in POLR1D (subunit of RNA polymerase I and II): exon2:c.T332C:p.L111P. Mutations in POLR1D are present in about 5% of individuals diagnosed with TCS. We propose that this mutation is causal in this family, suggesting a pathogenetic link between KFS and TCS. © 2014 Wiley Periodicals, Inc.

Fetus with Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of a Novel Association and Review of the Phenotype.

PubMed

Salinas-Torres, Victor M

2016-01-01

In 1981, Casamassima and colleagues described an autosomal recessive syndrome of spondylocostal dysostosis associated with anal and urogenital anomalies. Here, I describe 1 new fetus who presented with limb-body wall defect as a novel association, compile 7 patients, and review the clinical phenotype of Casamassima-Morton-Nance syndrome. This appears to be the 1st Casamassima-Morton-Nance syndrome fetus with this complex malformation. In light of this manifestation, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with significant clinical variability. Accordingly, it is proposed that Casamassima-Morton-Nance syndrome should be considered in those patients with the combination of a short and asymmetric thorax with rib and vertebral anomalies and scoliosis (spondylocostal-like pattern), anal atresia, absent external genitalia, renal and urethral abnormalities (caudal dysgenesis complex), craniofacial dysmorphic features (mainly flat nose with anteverted nares, low-set/abnormal ears, and short neck), hydrops, oligohydramnios, and a poor clinical outcome.

Syndromic intellectual disability: a new phenotype caused by an aromatic amino acid decarboxylase gene (DDC) variant.

PubMed

Graziano, Claudio; Wischmeijer, Anita; Pippucci, Tommaso; Fusco, Carlo; Diquigiovanni, Chiara; Nõukas, Margit; Sauk, Martin; Kurg, Ants; Rivieri, Francesca; Blau, Nenad; Hoffmann, Georg F; Chaubey, Alka; Schwartz, Charles E; Romeo, Giovanni; Bonora, Elena; Garavelli, Livia; Seri, Marco

2015-04-01

The causative variant in a consanguineous family in which the three patients (two siblings and a cousin) presented with intellectual disability, Marfanoid habitus, craniofacial dysmorphisms, chronic diarrhea and progressive kyphoscoliosis, has been identified through whole exome sequencing (WES) analysis. WES study identified a homozygous DDC variant in the patients, c.1123C>T, resulting in p.Arg375Cys missense substitution. Mutations in DDC cause a recessive metabolic disorder (aromatic amino acid decarboxylase, AADC, deficiency, OMIM #608643) characterized by hypotonia, oculogyric crises, excessive sweating, temperature instability, dystonia, severe neurologic dysfunction in infancy, and specific abnormalities of neurotransmitters and their metabolites in the cerebrospinal fluid (CSF). In our family, analysis of neurotransmitters and their metabolites in patient's CSF shows a pattern compatible with AADC deficiency, although the clinical signs are different from the classic form. Our work expands the phenotypic spectrum associated with DDC variants, which therefore can cause an additional novel syndrome without typical movement abnormalities. Copyright © 2015 Elsevier B.V. All rights reserved.

National Institute of Dental and Craniofacial Research

MedlinePlus

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

Psychological Effect of Prenatal Diagnosis of Cleft Lip and Palate: A Systematic Review.

PubMed

Sreejith, V P; Arun, V; Devarajan, Anooj P; Gopinath, Arjun; Sunil, Madhuri

2018-01-01

Cleft lip and/or palate is the most common congenital craniofacial anomaly. Prenatal diagnosis of the craniofacial anomalies is possible with the advent of newer imaging modalities. The identification of the defect at an early stage in the pregnancy helps the parents to be well informed and counseled regarding the treatment possibilities and outcomes of cleft lip and palate (CLP) treatment. To analyze the psychological effects of prenatal diagnosis of CLP on the parents. PubMed, Cochrane, and Google Scholar searches were made with search strings "prenatal diagnosis cleft lip palate," "antenatal diagnosis," "anomaly scan," "psychological effect cleft lip palate," and "prenatal counseling cleft lip palate." Of the results obtained, studies which evaluated the psychological aspects of parents of cleft children were further included in the study. Electronic search yielded 500 articles after duplication removal. Forty studies concentrated on the results of the scan and their implications predominantly in the diagnosis and management of cleft and other related abnormalities. Eight studies discussed the effects of prenatal diagnosis and counseling on the parents. Prenatal diagnosis enables appropriate and timely counseling of the parents by the cleft team and helps instill a sense of preparedness for the family which highly improves the quality of treatment received by the child enabling a near-to-normal quality and standard of life.

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

PubMed

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

2000-09-01

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

[The influence of breathing mode on the oral cavity].

PubMed

Surtel, Anna; Klepacz, Robert; Wysokińska-Miszczuk, Joanna

2015-12-01

Nose breathing is one of the key factors in the proper development and functioning of the oral cavity. The air passing through the nasal cavity is warmed and humidified while dust and other particulate matter is removed. It is also important as far as bone formation is concerned. The obstruction or congestions of the upper respiratory tract may negatively affect the correct and most optimal (nasal) respiratory tract. The switch from nasal to mouth breathing may lead to serious clinical consequences. Children with the clinical diagnosis of mouth breathing are usually pale, apathetic and they lack concentration and often get tired. Disorders resulting from hypoxy may also be the reason from sleep disturbances, such as frequent waking-up, nocturia, difficulties falling aslee. The main clinical manifestations of mouth breathing appear in the craniofacial structures. Mouth breathers frequently suffer from dental malocclusions and craniofacial bone abnormalities. Chronic muscle tension around the oral cavity could result in the widening of cranio-vertebral angle, posterior position of mandibula and narrow maxillary arch. Among dental alterations the most common are class II malocclusion (total or partial) with the protrusion of the anterior teeth, cross bite (unilateral or bilateral), anterior open bite and primary crowded teeth. Apart from malocclusion, chronic gingivitis, periodontitis, candida infections and halitosis are frequently present in mouth--breathing patients. © 2015 MEDPRESS.

Virtual Surgical Planning in Craniofacial Surgery

PubMed Central

Chim, Harvey; Wetjen, Nicholas; Mardini, Samir

2014-01-01

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

Craniofacial Surgery Fellowship Websites.

PubMed

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

2016-06-01

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

Understanding Cleft and Craniofacial Team Care

MedlinePlus

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Craniofacial Characteristics of Thalassemia Major Patients

PubMed Central

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

2016-01-01

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

Painful unilateral temporalis muscle enlargement: reactive masticatory muscle hypertrophy.

PubMed

Katsetos, Christos D; Bianchi, Michael A; Jaffery, Fizza; Koutzaki, Sirma; Zarella, Mark; Slater, Robert

2014-06-01

An instance of isolated unilateral temporalis muscle hypertrophy (reactive masticatory muscle hypertrophy with fiber type 1 predominance) confirmed by muscle biopsy with histochemical fiber typing and image analysis in a 62 year-old man is reported. The patient presented with bruxism and a painful swelling of the temple. Absence of asymmetry or other abnormalities of the craniofacial skeleton was confirmed by magnetic resonance imaging and cephalometric analyses. The patient achieved symptomatic improvement only after undergoing botulinum toxin injections. Muscle biopsy is key in the diagnosis of reactive masticatory muscle hypertrophy and its distinction from masticatory muscle myopathy (hypertrophic branchial myopathy) and other non-reactive causes of painful asymmetric temporalis muscle enlargement.

Familial multiple ventricular extrasystoles, short stature, craniofacial abnormalities and digital hypoplasia: a further case of Stoll syndrome?

PubMed

Mercer, Catherine L; Keeton, Barry; Dennis, Nicolas R

2008-04-01

We report two brothers, their mother and a maternal cousin who had a distinctive facial phenotype, mild brachydactyly and prominence of the interphalangeal joints. One brother and the mother also had multiple ventricular extrasystoles. Six other relatives in four generations were probably affected on the basis of history and family photographs. We also report a further individual from a different family with a similar facial phenotype, Pierre-Robin sequence, tapering fingers and multiple ventricular extrasystoles. These families have some similarities to those reported by Stoll et al. in a single family, showing dominant inheritance. Our patients would seem to have the same or a related condition.

Craniofacial orthodontics and postgraduate orthodontic training in Nigeria.

PubMed

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

2016-01-01

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

Applications of Computer Technology in Complex Craniofacial Reconstruction.

PubMed

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

2018-03-01

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

Severe Craniofacial Involvement due to Amniotic Band Sequence.

PubMed

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

2018-02-01

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

Antimicrobial surfaces for craniofacial implants: state of the art.

PubMed

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

2013-04-01

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

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

PubMed

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

2018-01-01

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

Adult psychological functioning of individuals born with craniofacial anomalies.

PubMed

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

1999-02-01

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

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

PubMed

L'Heureux-Lebeau, Bénédicte; Saliba, Issam

2014-09-01

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

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

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2011-06-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental.... Name of Committee: National Institute of Dental and Craniofacial Research Special Emphasis Panel... Officer, Scientific Review Branch, National Inst of Dental & Craniofacial Research, National Institutes of...

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

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2011-05-18

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

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2010-08-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and Craniofacial... Kelly, Scientific Review Officer, Scientific Review Branch, National Inst of Dental & Craniofacial...

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

PubMed

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

2005-01-01

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

Trisomy 15 mosaicism and uniparental disomy (UPD) in a liveborn infant

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

Milunsky, J.M.; Wyandt, H.E.; Amos, J.A.

We describe a liveborn infant with UPD in association with trisomy 15 mosaicism. Third trimester amniocentesis was performed for suspected IUGR. Results revealed 46,XX/47,XX,+15. The infant initially had respiratory distress and fed poorly. Symmetrical growth retardation, craniofacial dysmorphism, excess nuchal folds, a heart murmur, hypermobile joints, minor limb abnormalities, absent spontaneous movement and an abnormal cry were noted. Further study showed complex heart defects, including VSD and PDA, a left choroid plexus cyst, 13 ribs bilaterally, abnormal optic discs, abnormal visual evoked potentials and abnormal auditory brain stem responses. The infant died at 6 weeks of life from cardio-respiratory complications.more » Blood chromosomes were normal, 46,XX in 100 cells. Parental blood chromosomes were normal. Skin biopsy revealed 46,XX/47,XX,+15 in 40/50 (80%) cells as did autopsy lung tissue. Molecular analysis of the infant`s blood revealed maternal uniparental heterodisomy for chromosome 15 in the 46,XX cell line. Microsatellite analysis demonstrated that the extra chromosome originated from a maternal meiosis I nondisjunction. To our knowledge, this is the first liveborn infant with mosaic trisomy 15 and UPD in the diploid cells. Trisomy 15, heretofore, has been regarded as nonviable, even in mosaic form. While maternal UPD is associated with the Prader-Willi syndrome phenotype, mosaicism for trisomy 15 has been reported only when confined to the placenta. UPD in this case generally complicated prediction of the phenotype and raises the question whether all cases with UPD 15 should have more than one tissue studied to determine undetected trisomy 15.« less

Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities.

PubMed

Giri, Dinesh; Vignola, Maria Lillina; Gualtieri, Angelica; Scagliotti, Valeria; McNamara, Paul; Peak, Matthew; Didi, Mohammed; Gaston-Massuet, Carles; Senniappan, Senthil

2017-11-15

Congenital hypopituitarism (CH) is characterized by the deficiency of one or more pituitary hormones and can present alone or in association with complex disorders. Congenital hyperinsulinism (CHI) is a disorder of unregulated insulin secretion despite hypoglycaemia that can occur in isolation or as part of a wider syndrome. Molecular diagnosis is unknown in many cases of CH and CHI. The underlying genetic etiology causing the complex phenotype of CH and CHI is unknown. In this study, we identified a de novo heterozygous mutation in the developmental transcription factor, forkhead box A2, FOXA2 (c.505T>C, p.S169P) in a child with CHI and CH with craniofacial dysmorphic features, choroidal coloboma and endoderm-derived organ malformations in liver, lung and gastrointestinal tract by whole exome sequencing. The mutation is at a highly conserved residue within the DNA binding domain. We demonstrated strong expression of Foxa2 mRNA in the developing hypothalamus, pituitary, pancreas, lungs and oesophagus of mouse embryos using in situ hybridization. Expression profiling on human embryos by immunohistochemistry showed strong expression of hFOXA2 in the neural tube, third ventricle, diencephalon and pancreas. Transient transfection of HEK293T cells with Wt (Wild type) hFOXA2 or mutant hFOXA2 showed an impairment in transcriptional reporter activity by the mutant hFOXA2. Further analyses using western blot assays showed that the FOXA2 p.(S169P) variant is pathogenic resulting in lower expression levels when compared with Wt hFOXA2. Our results show, for the first time, the causative role of FOXA2 in a complex congenital syndrome with hypopituitarism, hyperinsulinism and endoderm-derived organ abnormalities. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.

PubMed

Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison; Pupavac, Mihaela; Geiger, Elizabeth A; Watson, Abigail; Castro, Victoria L; Cheung, Warren; Chen, Shu-Huang; Watkins, David; Pastinen, Tomi; Skovby, Flemming; Appel, Bruce; Rosenblatt, David S; Shaikh, Tamim H

2017-08-01

CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

MEMO1 drives cranial endochondral ossification and palatogenesis

PubMed Central

Otterloo, Eric Van; Feng, Weiguo; Jones, Kenneth L; Hynes, Nancy E; Clouthier, David E; Niswander, Lee; Williams, Trevor

2016-01-01

The cranial base is a component of the neurocranium and has a central role in the structural integration of the face, brain and vertebral column. Consequently, alteration in the shape of the human cranial base has been intimately linked with primate evolution and defective development is associated with numerous human facial abnormalities. Here we describe a novel recessive mutant mouse strain that presented with a domed head and fully penetrant cleft secondary palate coupled with defects in the formation of the underlying cranial base. Mapping and non-complementation studies revealed a specific mutation in Memo1 - a gene originally associated with cell migration. Expression analysis of Memo1 identified robust expression in the perichondrium and periosteum of the developing cranial base, but only modest expression in the palatal shelves. Fittingly, although the palatal shelves failed to elevate in Memo1 mutants, expression changes were modest within the shelves themselves. In contrast, the cranial base, which forms via endochondral ossification had major reductions in the expression of genes responsible for bone formation, notably matrix metalloproteinases and markers of the osteoblast lineage, mirrored by an increase in markers of cartilage and extracellular matrix development. Concomitant with these changes, mutant cranial bases showed an increased zone of hypertrophic chondrocytes accompanied by a reduction in both vascular invasion and mineralization. Finally, neural crest cell-specific deletion of Memo1 caused a failure of anterior cranial base ossification indicating a cell autonomous role for MEMO1 in the development of these neural crest cell derived structures. However, palate formation was largely normal in these conditional mutants, suggesting a non-autonomous role for MEMO1 in palatal closure. Overall, these findings assign a new function to MEMO1 in driving endochondral ossification in the cranium, and also link abnormal development of the cranial base with more widespread effects on craniofacial shape relevant to human craniofacial dysmorphology. PMID:26746790

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.

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.

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Reproduction, embryonic development, and maternal transfer of contaminants in the amphibian Gastrophryne carolinensis

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

Hopkins, W.A.; DuRant, S.E.; Staub, B.P.

2006-05-15

Although many amphibian populations around the world are declining at alarming rates, the cause of most declines remains unknown. Environmental contamination is one of several factors implicated in declines and may have particularly important effects on sensitive developmental stages. We examined maternal transfer of contaminants in eastern narrow-mouth toads (Gastrophryne carolinensis) collected from a reference site and near a coal-burning power plant. Adult toads inhabiting the industrial area transferred significant quantities of selenium and strontium to their eggs, but Se concentrations were most notable (up to 100 {mu} g/g dry mass). Compared with the reference site, hatching success was reducedmore » by 11% in clutches from the contaminated site. In surviving larvae, the frequency of developmental abnormalities and abnormal swimming was 55-58% higher in the contaminated site relative to the reference site. Craniofacial abnormalities were nearly an order of magnitude more prevalent in hatchlings from the contaminated site. When all developmental criteria were considered collectively, offspring from the contaminated site experienced 19% lower viability. Although there was no statistical relationship between the concentration of Se or Sr transferred to eggs and any measure of offspring viability, our study demonstrates that maternal transfer may be an important route of contaminant exposure in amphibians that has been overlooked.« less

Novel compound heterozygous DPH1 mutations in a patient with the unique clinical features of airway obstruction and external genital abnormalities.

PubMed

Nakajima, Junya; Oana, Shingo; Sakaguchi, Tomohiro; Nakashima, Mitsuko; Numabe, Hironao; Kawashima, Hisashi; Matsumoto, Naomichi; Miyake, Noriko

2018-04-01

The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901). To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. The clinical phenotype of all patients with DPH1 mutations, including the current patient, revealed core features, although the external genital anomaly was newly recognized in our case.

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

PubMed Central

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

2011-01-01

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

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Orthognathic Surgery in Craniofacial Microsomia: Treatment Algorithm

PubMed Central

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

2015-01-01

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

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

PubMed

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

2014-06-01

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

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

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

PubMed

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

2014-10-01

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

Duplication of the EFNB1 Gene in Familial Hypertelorism: Imbalance in Ephrin-B1 Expression and Abnormal Phenotypes in Humans and Mice

PubMed Central

Babbs, Christian; Stewart, Helen S; Williams, Louise J; Connell, Lyndsey; Goriely, Anne; Twigg, Stephen RF; Smith, Kim; Lester, Tracy; Wilkie, Andrew OM

2011-01-01

Familial hypertelorism, characterized by widely spaced eyes, classically shows autosomal dominant inheritance (Teebi type), but some pedigrees are compatible with X-linkage. No mechanism has been described previously, but clinical similarity has been noted to craniofrontonasal syndrome (CFNS), which is caused by mutations in the X-linked EFNB1 gene. Here we report a family in which females in three generations presented with hypertelorism, but lacked either craniosynostosis or a grooved nasal tip, excluding CFNS. DNA sequencing of EFNB1 was normal, but further analysis revealed a duplication of 937 kb including EFNB1 and two flanking genes: PJA1 and STARD8. We found that the X chromosome bearing the duplication produces ∼1.6-fold more EFNB1 transcript than the normal X chromosome and propose that, in the context of X-inactivation, this difference in expression level of EFNB1 results in abnormal cell sorting leading to hypertelorism. To support this hypothesis, we provide evidence from a mouse model carrying a targeted human EFNB1 cDNA, that abnormal cell sorting occurs in the cranial region. Hence, we propose that X-linked cases resembling Teebi hypertelorism may have a similar mechanism to CFNS, and that cellular mosaicism for different levels of ephrin-B1 (as well as simple presence/absence) leads to craniofacial abnormalities. Hum Mutat 32:1–9, 2011. © 2011 Wiley-Liss, Inc. PMID:21542058

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

PubMed Central

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

2016-01-01

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

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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

A novel heterozygous SOX2 mutation causing anophthalmia/microphthalmia with genital anomalies.

PubMed

Pedace, Lucia; Castori, Marco; Binni, Francesco; Pingi, Alberto; Grammatico, Barbara; Scommegna, Salvatore; Majore, Silvia; Grammatico, Paola

2009-01-01

Anophthalmia/microphthalmia is a rare developmental craniofacial defect, which recognizes a wide range of causes, including chromosomal abnormalities, single-gene mutations as well as environmental factors. Heterozygous mutations in the SOX2 gene are the most common monogenic form of anophthalmia/microphthalmia, as they are reported in up to 10-15% cases. Here, we describe a sporadic patient showing bilateral anophthalmia/microphthalmia and micropenis caused by a novel mutation (c.59_60insGG) in the SOX2 gene. Morphological and endocrinological evaluations excluded any anomaly of the hypothalamus-pituitary axis. Our finding supports the hypothesis that SOX2 is particularly prone to slipped-strand mispairing, which results in a high frequency of point deletions/insertions.

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

PubMed

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

2015-01-01

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

Goldenhar syndrome: Cardiac anesthesiologist's perspective.

PubMed

Choudhury, Minati; Kapoor, Poonam Malhotra

2017-01-01

Goldenhar syndrome or oculo-auriculo-vertebral dysplasia was defined by Goldenhar in 1952 and redefined by Grolin et al. later. As the name denotes, children with this syndrome present with craniofacial and vertebral anomalies which increase the risk of airway compromise. Neonates and infants with this syndrome often have premature internal organs, low birth weight, and airway disorders. For this reason, safe anesthesia in such infants requires a complete knowledge regarding metabolism and side effects of the drugs. The association of cardiovascular abnormalities is not uncommon and possesses additional challenge for anesthetic management. The aim of this review is to draw attention to the various perioperative problems that can be faced in these infants when they undergo surgery or the correction of the underlying cardiac problem.

Transvenous embolization in spontaneous direct carotid-cavernous fistula in childhood

PubMed Central

Mercado, Glenna B.; Irie, Keiko; Negoro, Makoto; Moriya, Shigeta; Tanaka, Teppei; Ohmura, Masahiro; Sadato, Akiyo; Hayakawa, Motuharu; Sano, Hirotoshi

2011-01-01

Carotid cavernous fistula (CCF) is an abnormal arteriovenous communication in the cavernous sinus. Direct CCF results from a tear in the intracavernous carotid artery. Typically, it has a high flow and usually presents with oculo-orbital venous congestive features such as exophthalmos, chemosis, and sometimes oculomotor or abducens cranial nerve palsy. Indirect CCF generally occurs spontaneously with subtle signs. We report a rare case of spontaneous direct CCF in childhood who did not have the usual history of craniofacial trauma or connective tissue disorder but presented with progressive chemosis and exophthalmos of the right eye. This report aims also to describe the safety and success of transvenous embolization with coils of the superior ophthalmic vein and cavernous sinus through the inferior petrosal sinus. PMID:22059104

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-08-03

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

Novel autosomal dominant mandibulofacial dysostosis with ptosis: clinical description and exclusion of TCOF1

PubMed Central

Hedera, P; Toriello, H; Petty, E

2002-01-01

Methods: Six affected family members underwent a complete medical genetics physical examination and two affected subjects had skeletal survey. All available medical records were reviewed. Linkage analysis using the markers spanning the TCOF1 locus was performed. One typically affected family member had a high resolution karyotype. Results: Affected subjects had significant craniofacial abnormalities without any significant acral changes and thus had a phenotype consistent with a MFD variant. Distinctive features included hypoplasia of the zygomatic complex, micrognathia with malocclusion, auricular abnormalities with conductive hearing loss, and ptosis. Significantly negative two point lod scores were obtained for markers spanning the TCOF1 locus, excluding the possibility that the disease in our kindred is allelic with TCS. High resolution karyotype was normal. Conclusions: We report a kindred with a novel type of MFD that is not linked to the TCOF1 locus and is also clinically distinct from other types of AD MFD. Identification of additional families will facilitate identification of the gene causing this type of AD MFD and further characterisation of the clinical phenotype. PMID:12114479

The epidemiology of adult obstructive sleep apnea.

PubMed

Punjabi, Naresh M

2008-02-15

Obstructive sleep apnea is a chronic condition characterized by frequent episodes of upper airway collapse during sleep. Its effect on nocturnal sleep quality and ensuing daytime fatigue and sleepiness are widely acknowledged. Increasingly, obstructive sleep apnea is also being recognized as an independent risk factor for several clinical consequences, including systemic hypertension, cardiovascular disease, stroke, and abnormal glucose metabolism. Estimates of disease prevalence are in the range of 3% to 7%, with certain subgroups of the population bearing higher risk. Factors that increase vulnerability for the disorder include age, male sex, obesity, family history, menopause, craniofacial abnormalities, and certain health behaviors such as cigarette smoking and alcohol use. Despite the numerous advancements in our understanding of the pathogenesis and clinical consequences of the disorder, a majority of those affected remain undiagnosed. Simple queries of the patient or bed-partner for the symptoms and signs of the disorder, namely, loud snoring, observed apneas, and daytime sleepiness, would help identify those in need of further diagnostic evaluation. The primary objective of this article is to review some of the epidemiologic aspects of obstructive sleep apnea in adults.

A comprehensive analysis of craniofacial trauma.

PubMed

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

1994-01-01

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

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

PubMed

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

1999-01-01

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

Biomaterials and biologics in craniofacial reconstruction.

PubMed

Engstrand, Thomas

2012-01-01

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

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

PubMed

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

2016-01-01

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

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

PubMed

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

2007-09-01

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

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

PubMed

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

2014-05-01

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

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

PubMed Central

Fish, Jennifer L.; Schneider, Richard A.

2014-01-01

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

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

PubMed Central

Szabó, C. Ákos; Patel, Mayuri; Uteshev, Victor V.

2016-01-01

The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons’ electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status. PMID:26924854

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

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

Customized Polymethyl Methacrylate Implants for the Reconstruction of Craniofacial Osseous Defects

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed

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

1998-12-01

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

Craniofacial reconstruction evaluation by geodesic network.

PubMed

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

2014-01-01

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

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

PubMed

Davidopoulou, Sotiria; Chatzigianni, Athina

2017-12-01

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

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

PubMed Central

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

2014-01-01

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

How do we recognize the child with OSAS?

PubMed

Joosten, Koen F; Larramona, Helena; Miano, Silvia; Van Waardenburg, Dick; Kaditis, Athanasios G; Vandenbussche, Nele; Ersu, Refika

2017-02-01

Obstructive sleep-disordered breathing includes a spectrum of clinical entities with variable severity ranging from primary snoring to obstructive sleep apnea syndrome (OSAS). The clinical suspicion for OSAS is most often raised by parental report of specific symptoms and/or abnormalities identified by the physical examination which predispose to upper airway obstruction (e.g., adenotonsillar hypertrophy, obesity, craniofacial abnormalities, neuromuscular disorders). Symptoms and signs of OSAS are classified into those directly related to the intermittent pharyngeal airway obstruction (e.g., parental report of snoring, apneic events) and into morbidity resulting from the upper airway obstruction (e.g., increased daytime sleepiness, hyperactivity, poor school performance, inadequate somatic growth rate or enuresis). History of premature birth and a family history of OSAS as well as obesity and African American ethnicity are associated with increased risk of sleep-disordered breathing in childhood. Polysomnography is the gold standard method for the diagnosis of OSAS but may not be always feasible, especially in low-income countries or non-tertiary hospitals. Nocturnal oximetry and/or sleep questionnaires may be used to identify the child at high risk of OSAS when polysomnography is not an option. Endoscopy and MRI of the upper airway may help to identify the level(s) of upper airway obstruction and to evaluate the dynamic mechanics of the upper airway, especially in children with combined abnormalities. Pediatr Pulmonol. 2017;52:260-271. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pediatric considerations in craniofacial trauma.

PubMed

Koch, Bernadette L

2014-08-01

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

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

PubMed

Fijikami, T K; Cedeño Pacheco, E

1991-01-01

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

Advances in Bioprinting Technologies for Craniofacial Reconstruction.

PubMed

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

2016-09-01

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

Alcohol and the developing fetus--a review.

PubMed

Chaudhuri, J D

2000-01-01

Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. It is characterized mainly by physical and mental retardation, craniofacial anomalies and minor joint abnormalities. However, with the increasing incidence of FAS, there is a great variation in the clinical features of FAS. This article describes in detail these clinical features. Due to ethical reasons it is not possible to perform experiments on pregnant women. Hence to study the effects of alcohol, various animal and avian experimental models have been chosen. The various experimental findings and human correlation are described. The exact mechanism by which alcohol induces its teratogenic effects is not known. The possible mechanisms are discussed. Measures to prevent the occurrence of FAS have been suggested.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-01-21

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-06-01

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

Biomaterials for Craniofacial Bone Engineering

PubMed Central

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

2014-01-01

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

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

Noda, Kazuo, E-mail: knoda@kuhp.kyoto-u.ac.jp; Nakamura, Tomoyuki; Komatsu, Yoshihiro

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice weremore » less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.« less

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

PubMed Central

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

2017-01-01

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

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

PubMed

Fantauzzo, Katherine A; Soriano, Philippe

2016-11-01

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

Craniofacial melorheostosis.

PubMed

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

2008-01-01

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

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

PubMed

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

2015-09-01

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

Craniofacial neurofibromatosis: treatment of the midface deformity.

PubMed

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

2014-07-01

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

Cranio-facial clefts in pre-hispanic America.

PubMed

Marius-Nunez, A L; Wasiak, D T

2015-10-01

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

FishFace: interactive atlas of zebrafish craniofacial development at cellular resolution

PubMed Central

2013-01-01

Background The vertebrate craniofacial skeleton may exhibit anatomical complexity and diversity, but its genesis and evolution can be understood through careful dissection of developmental programs at cellular resolution. Resources are lacking that include introductory overviews of skeletal anatomy coupled with descriptions of craniofacial development at cellular resolution. In addition to providing analytical guidelines for other studies, such an atlas would suggest cellular mechanisms underlying development. Description We present the Fish Face Atlas, an online, 3D-interactive atlas of craniofacial development in the zebrafish Danio rerio. Alizarin red-stained skulls scanned by fluorescent optical projection tomography and segmented into individual elements provide a resource for understanding the 3D structure of the zebrafish craniofacial skeleton. These data provide the user an anatomical entry point to confocal images of Alizarin red-stained zebrafish with transgenically-labelled pharyngeal arch ectomesenchyme, chondrocytes, and osteoblasts, which illustrate the appearance, morphogenesis, and growth of the mandibular and hyoid cartilages and bones, as viewed in live, anesthetized zebrafish during embryonic and larval development. Confocal image stacks at high magnification during the same stages provide cellular detail and suggest developmental and evolutionary hypotheses. Conclusion The FishFace Atlas is a novel learning tool for understanding craniofacial skeletal development, and can serve as a reference for a variety of studies, including comparative and mutational analyses. PMID:23714426

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

PubMed

Townsend, G C; Brook, A H

2014-06-01

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

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

PubMed

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

2018-02-01

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

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

PubMed

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

2011-11-01

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

Body Image and Quality of Life in Adolescents With Craniofacial Conditions

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-12-01

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

Further delineation of the SATB2 phenotype.

PubMed

Döcker, Dennis; Schubach, Max; Menzel, Moritz; Munz, Marita; Spaich, Christiane; Biskup, Saskia; Bartholdi, Deborah

2014-08-01

SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex. In humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2 haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and intellectual disability (ID). A single patient carrying a nonsense mutation in SATB2 has been described to date. In this study, we performed trio-exome sequencing in a 3-year-old girl with CP and severely delayed speech development, and her unaffected parents. Previously, the girl had undergone conventional and molecular karyotyping (microarray analysis), as well as targeted analysis for different diseases associated with developmental delay, including Angelman syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be established. Exome sequencing revealed a de novo nonsense mutation in the SATB2 gene (c.715C>T; p.R239*). The identification of a second patient carrying a de novo nonsense mutation in SATB2 confirms that this gene is essential for normal craniofacial patterning and cognitive development. Based on our data and the literature published so far, we propose a new clinically recognizable syndrome - the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and should be considered in children with ID, severe speech delay, cleft or high-arched palate and abnormal dentition with crowded and irregularly shaped teeth.

Respiratory disorders in paediatric age: orthodontic diagnosis and treatment in dysmetabolic obese children and allergic slim children.

PubMed

Favero, L; Arreghini, A; Cocilovo, F; Favero, V

2013-09-01

Obesity and allergic susceptibility are worsening problems in the most industrialised countries. With different mechanisms, they both lead to a deterioration of children's life quality because they affect the respiratory system, leading to asthma and respiratory disorders such as mouth breathing and obstructive sleep apnoea. The latter are related to specific types of malocclusions that require an early diagnosis and specific multidisciplinary treatment. The purpose of this work is to show the characteristic signs and symptoms of these disorders in children of the two phenotypes (allergic and slim, obese and dysmetabolic). Intercepting such issues allows both pediatricians and paediatric dentists to refer the child to a multidisciplinary team of specialists able to deal, in a holistic way, with both the physical and behavioural causes, and also with the consequences on systemic and craniofacial development in particular. The literature available on this topic in the years between 1997 and 2011 was reviewed, paying special attention to prevention, paediatric visits, diagnostic tools and treatment options for each of the two conditions. Dysmetabolic obese children and allergic slim children have specific respiratory problems during rest and exercise. Mouth breathing and obstructive sleep apnoea are due to an abnormal craniofacial development and can cause serious systemic problems in adulthood. Intercepting early signs of pathognomonic symptoms of sleep aponea and mouth breathing permits to treat children with an early multidisciplinary approach, and allows for proper physical and psychological development of the child.

Prostate Cancer Progression and Serum Sibling (Small Integrin Binding N-Linked Glycoprotein) Levels

DTIC Science & Technology

2008-10-01

Alka Jain,2 Matt Tayback,2 and Neal S. Fedarko2 1Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research... Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, U.S.A. 2Division of Geriatrics, Department of Medicine, Johns Hopkins University, School of...hypophosphatemia [ Carey et al., 1986]. We have previously reported on a patient with LSNS and hypophosphatemia where the plasma phosphatonin, fibroblast

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

PubMed

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

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

Biomaterials in craniofacial reconstruction.

PubMed

Cho, Younghoon R; Gosain, Arun K

2004-07-01

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

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

PubMed

Baumrind, Sheldon; Curry, Sean

2015-08-01

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

Craniofacial reconstruction - series (image)

MedlinePlus

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

Variability of the cranial and dental phenotype in Williams syndrome.

PubMed

Axelsson, Stefan

2005-01-01

Williams syndrome (WS) is a rare congenital disorder involving the cardiovascular system, connective tissue, and the central nervous system, resulting in mild to moderate mental retardation, a specific cognitive profile, unique personality characteristics, distinctive facial features, and cardiovascular disease. The majority of individuals with a clinical diagnosis of WS have a contiguous gene deletion at chromosome 7 (7q11.23). Physical features include characteristic facial features with full prominent cheeks, wide mouth, long philtrum, small nose with depressed nasal bridge, heavy orbital ridges, medial eyebrow flare, dental abnormalities, hoarse voice, growth retardation, and cardiovascular abnormalities (most commonly supravalvular aortic stenosis and/or peripheral pulmonary artery stenosis). The cognitive profile is distinctive, consisting of strengths in auditory memory, language, and face-processing, but extreme weakness in visuospatial, numerical and problem-solving abilities. Neurological studies have identified a significantly decreased brain volume in adult individuals with WS with relatively normal development of the limbic, frontal and cerebellar structures. The aims were to analyse the neurocranium, the craniofacial region, and the dentition in a well defined Norwegian group of individuals with WS. In order to accomplish this, normative cephalometric standards for the neurocranium, including the cranial base and the sella turcica, were established for Norwegian males and females from 6 to 21 years of age, using lateral radiographic cephalograms from the Oslo University Craniofacial Growth Archive. The study material comprised radiographic lateral cephalograms, orthopantomograms and dental casts from 62 individuals with WS ranging from 4 to 44 years. The lateral cephalograms, orthopantomograms and dental casts were analysed using standard methods reported in the literature. Neurocranium: The results from the cephalometric analyses showed that the size and shape of the neurocranium in WS differed from normal controls. A flattening of the superior aspect of the parietal bone was found and the posterior prominence of the occipital bone was larger. These findings were in concordance with published neuroanatomical/neuropathological studies on WS and fit well with the reported anatomical aberrations in the WS brain, e.g. a smaller brain volume where some parts are of relatively normal size while others are decreased. The anterior and posterior cranial base was shorter in WS, but with a normal cranial base angle. The thickness of the calvarian bones, especially the frontal and occipital bones, was greater in WS than in normal controls. Sella turcica: The size of the sella turcica was somewhat smaller in WS compared with normal controls, though not significant. Aberrant types of shape of the sella turcica in WS are demonstrated. The correlation between prenatal malformation in the pituitary gland/sella turcica and the postnatal morphology of the sella turcica is discussed. The craniofacial skeleton: Two areas, in addition to the cranial base, have been identified to contribute to the characteristic facial appearance in WS; the anterior inclination of the maxilla, and the shape of the mandible. The severely deficient bony chin in combination with the high mandibular plane angle can explain earlier clinical descriptions of a retrusive mandible in WS. Frequent mouth breathing during childhood and the smaller cranial base may be associated with the characteristic craniofacial pattern. Dentition: In individuals with WS over 10 years of age 40.5 per cent had agenesis of one or more permanent teeth and 11.9 percent had agenesis of 6 teeth or more. The missing permanent teeth in the maxilla most commonly included 2nd premolars, 1st premolars, and lateral incisors. In the mandible most commonly 2nd premolars, 1st premolars, and central incisors were absent. The tooth crowns of permanent teeth were smaller, both in the mesio-distal and labio-lingual dimension. The permanent tooth crowns have several characteristic deviations from normal shape; especially incisors in both jaws were tapered or screwdriver-shaped. An evaluation of taurodontism on permanent molars was performed. However, most of the molars rated as being taurodontic had short total tooth lengths and could thus be rated taurodontic without meeting the classical definition. These studies have shown aberrations in the neurocranium including the sella turcica in WS not previously reported. In the craniofacial skeleton specific traits have been identified to contribute to the characteristic facial appearance in WS. Dental aberrations in the permanent dentition including agenesis, smaller size, and aberrant shape of teeth, are common in WS.

[A case of partial 1p36.1 deletion and partial trisomy 6p diagnosed by karyotype].

PubMed

Fernández Pineda, Monica; Ramírez-Cheyne, Julián; Isaza, Carolina; Saldarriaga, Wilmar

The deletion of chromosomal region 1p36 is one of the most common sub-telomeric microdeletion syndromes and has distinctive dysmorphic features. On the other hand, partial trisomy of the short arm of chromosome 6 is a rare chromosomal abnormality with a variable phenotype. To report a case with both chromosome abnormalities, and to highlight the importance of the karyotype as a diagnostic tool in dysmorphology. The case of is presented of a two month-old infant with several craniofacial anomalies, neck haemangioma, sacral pit, rhizomelic shortening, small hands and feet, left unilateral cryptorchidism, and hypotonia. The infant also suffered intrauterine growth restriction and is the product of the eighth pregnancy of a 28 years old woman. Due to the unspecific findings in phenotype, a karyotype was requested, which showed a partial deletion of 1p36.1 and a partial trisomy of chromosome 6. The development of new techniques in molecular biology has improved diagnostic possibilities in medical genetics. However, the traditional karyotype remains as an important diagnostic tool in patients with multiple congenital anomalies. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

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

PubMed

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

2014-09-01

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

Craniofacial morphology and sleep apnea in children with obstructed upper airways: differences between genders.

PubMed

Di Francesco, Renata; Monteiro, Roberta; Paulo, Maria Luiza de Melo; Buranello, Fernando; Imamura, Rui

2012-06-01

To correlate sleep apnea with craniofacial characteristics and facial patterns according to gender. In this prospective survey we studied 77 male and female children (3-12 years old) with an upper airway obstruction due to tonsil and adenoid enlargement. Children with lung problems, neurological disorders and syndromes, obstructive septal deviation, previous orthodontic treatment, orthodontic surgeries or oral surgeries, or obesity were excluded. Patients were subjected to physical examinations, nasal fiberoptic endoscopy, teleradiography for cephalometric analysis, and polysomnography. Cephalometric analysis included the following skeletal craniofacial measurements: facial axis (FA), facial depth (FD), mandibular plane angle (MP), lower facial height (LFH), mandibular arch (MA), and vertical growth coefficient (VERT) index. The prevalence of sleep apnea was 46.75% with no statistical difference between genders. Among children with obstructive sleep apnea (Apneia Hypopnea Index - AHI ≥ 1) boys had higher AHI values than girls. A predominance of the dolichofacial pattern (81.9%) was observed. The following skeletal craniofacial measurements correlated with AHI in boys: FD (r(s)=-0.336/p=0.020), MP (r(s)=0.486/p=0.00), and VERT index (r(s)=-0.337/p=0.019). No correlations between craniofacial measurements and AHI were identified in girls. Craniofacial morphology may influence the severity of sleep apnea in boys but not in girls. Copyright © 2012 Elsevier B.V. All rights reserved.

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

The genesis of craniofacial biology as a health science discipline.

PubMed

Sperber, G H; Sperber, S M

2014-06-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

Parthasarathy, Jayanthi

2014-01-01

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

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

PubMed

Dobson, Hannah; Wall, Steven

2016-11-01

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

Injectable scaffolds: Preparation and application in dental and craniofacial regeneration

PubMed Central

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

2016-01-01

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

Melorheostosis involving the craniofacial skeleton.

PubMed

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

2004-11-01

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

Development of an Ocular and Craniofacial Trauma Treatment Training System

DTIC Science & Technology

2013-08-01

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

Mechanisms that Underlie Co-variation of the Brain and Face

PubMed Central

Marcucio, Ralph S.; Young, Nathan M.; Hu, Diane; Hallgrimsson, Benedikt

2011-01-01

The effect of the brain on the morphology of the face has long been recognized in both evolutionary biology and clinical medicine. In this paper we describe factors that are active between development of the brain and face and how these might impact craniofacial variation. First, there is the physical influence of the brain, which contributes to overall growth and morphology of the face through direct structural interactions. Second, there is the molecular influence of the brain, which signals to facial tissues to establish signaling centers that regulate patterned growth. Importantly, subtle alterations to these physical or molecular interactions may contribute to both normal and abnormal variation. These interactions are therefore critical to our understanding of how a diversity of facial morphologies can be generated both within species and across evolutionary time. PMID:21381182

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

PubMed

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

2014-08-01

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

Overexpression of esterase D in kidney from trisomy 13 fetuses.

PubMed Central

Loughna, S; Bennett, P; Gau, G; Nicolaides, K; Blunt, S; Moore, G

1993-01-01

Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. Images Figure 1 Figure 2 Figure 3 PMID:8213811

PET/CT and MRI of intra-osseous haemangioma of the tibia

PubMed Central

Cha, J G; Yoo, J H; Kim, H K; Park, J M; Paik, S H; Park, S J

2012-01-01

Intra-osseous haemangioma is a rare, benign neoplasm that usually involves the vertebrae and craniofacial bones. Furthermore, its occurrence in the long bones is extremely rare. We report the findings of fluorine-18-fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT and MRI in a patient with intra-osseous haemangioma in the proximal tibia, who was initially misdiagnosed as having a malignancy based on 18F-FDG PET/CT. 18F-FDG PET/CT showed a well-marginated osteolytic lesion with abnormal FDG uptake. The mass demonstrated low signal intensity on T1 weighted MRI. On T2 weighted images, the lesion appeared as a cluster of high signal intensity lobules and showed strong enhancement on contrast-enhanced T1 weighted images. Surgical curettage was performed and histopathological examination of the excised tissue confirmed a cavernous haemangioma. PMID:22457416

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of PITX2 and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay.

PubMed

Maldžienė, Živilė; Preikšaitienė, Eglė; Ignotienė, Salomėja; Kapitanova, Natalija; Utkus, Algirdas; Kučinskas, Vaidutis

2017-01-01

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of autosomal dominantly inherited malformations that predominantly affect the eye but are also associated with craniofacial dysmorphism and dental abnormalities. A broad spectrum of genetic alterations involving PITX2 and FOXC1 lead to ARS. We report on a 4-year-old girl with clinical features of ARS and developmental delay due to a de novo apparently balanced pericentric inversion in chromosome 4. This report emphasizes that complementary investigations are necessary to precisely characterize chromosomal rearrangements. Elucidation of the exact genetic cause of ARS is important for comprehensive genetic counseling of the family members and for better patient management. © 2017 S. Karger AG, Basel.

Partial trisomy of chromosome 22 resulting from a supernumerary marker chromosome 22 in a child with features of cat eye syndrome.

PubMed

Bélien, Valérie; Gérard-Blanluet, Marion; Serero, Stéphane; Le Dû, Nathalie; Baumann, Clarisse; Jacquemont, Marie-Line; Dupont, Céline; Krabchi, Kada; Drunat, Séverine; Elbez, Annie; Janaud, Jean-Claude; Benzacken, Brigitte; Verloes, Alain; Tabet, Anne-Claude; Aboura, Azzedine

2008-07-15

Small supernumerary marker chromosomes are present in about 0.05% of the human population. In approximately 28% of persons with these markers (excluding the approximately 60% derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. We report on a 3-month-old girl with intrauterine growth retardation, craniofacial features, hypotonia, partial coloboma of iris and total anomalous pulmonary venous return. Cytogenetic analysis showed the presence of a supernumerary marker chromosome, identified by fluorescence in situ hybridization as part of chromosome 22, and conferring a proximal partial trisomy 22q22.21, not encompassing the DiGeorge critical region (RP11-154H4 + , TBX1-). This observation adds new information relevant to cat eye syndrome and partial trisomy of 22q. 2008 Wiley-Liss, Inc.

Morphological and behavioral responses of zebrafish after 24h of ketamine embryonic exposure.

PubMed

Félix, Luís M; Serafim, Cindy; Martins, Maria J; Valentim, Ana M; Antunes, Luís M; Matos, Manuela; Coimbra, Ana M

2017-04-15

Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24h-LC 50 was calculated from percent survival using probit analysis. Based on the 24h-LC 50 (94.4mgL -1 ), embryos (2hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24h to ketamine concentrations of 50, 70 or 90mgL -1 . Developmental parameters were evaluated on the course of the experimental period, and anatomical abnormalities and locomotor deficits were analyzed at 144hpf. Although the portion of ketamine transferred into the embryo was higher in the lowest exposed group (about 0.056±0.020pmol per embryo), the results showed that endpoints such as increased mortality, edema, heart rate alterations, malformation and abnormal growth rates were significantly affected. At 144hpf, the developmental abnormalities included thoracic and trunk abnormalities in the groups exposed to 70 and 90mgL -1 . Defects in cartilage (alcian blue) and bone (calcein) elements also corroborated the craniofacial anomalies observed. A significant up-regulation of the development-related gene nog3 was detected by qRT-PCR at 8 hpf. Early exposure to ketamine also resulted in long-term behavioral changes, such as an increase in thigmotaxis and disruption of avoidance behavior at 144 hpf. Altogether, this study provides new evidence on the ketamine teratogenic potential, indicating a possible pharmacological impact of ketamine in aquatic environments. Copyright © 2017 Elsevier Inc. All rights reserved.

An embryological point of view on associated congenital anomalies of children with Hirschsprung disease.

PubMed

Slavikova, T; Zabojnikova, L; Babala, J; Varga, I

2015-01-01

The most common congenital gut motility disorder is the Hirschsprung disease (HSCR). This anomaly is characterized by absence of neural crest-derived enteric neuronal ganglia. The aim of our study was to analyze the relationship between HSCR and other congenital anomalies or malfunctions. We examined 130 patients with Hirschsprung disease from Slovakia for last 10 years. During patients examination we focused not only on morphological abnormalities, but also functional anomalies. The incidence of associated congenital anomalies in our patients with HSCR was 26.1 %. But if we add functional defects (hypothyroidism, malfunction in cellular immunity, neurological deficit) to the morphological congenital abnormalities, the rate of the patients with HSCR with additional defects achieves 50.1 %. Nine of our patients (6.9 %) had syndromic HSCR. The most frequent disorder (13.6 % of patients) was primary deficiency in cellular immunity. More than 12.3 % of patients with HSCR had genitourinary abnormalities, in 10.0 % of patients variable degree of psychomotor retardation was observed, and skeletal, muscle and limb anomalies involved 7.7 % of patients. In 7.6 % cases of patients we found congenital hypothyroidism (including 2 cases of agenesis of thyroid gland). More than 6.1 % of patients presented with an associated anomaly in gastrointestinal tract (mostly anorectal malformations). Up to 5.5 % patients had congenital anomaly of heart, 3.8 % had ophthalmic and 3.1 % had craniofacial anomalies. Down syndrome was the main diagnosis in 3.8 % patients. We discussed  the relationship between HSCR and other anomalies, which are probably caused by abnormal migration, proliferation, or differentiation, of neural crest cells during embryogenesis (Tab. 1, Fig. 2, Ref. 75).

Siamese twins with craniofacial duplication and bilateral cleft lip/palate in a ceramic representation of the Chimú culture (Peru): a comparative analysis with a current case.

PubMed

Pachajoa, Harry; Hernandez-Amaris, Maria F; Porras-Hurtado, Gloria Liliana; Rodriguez, Carlos A

2014-06-01

Craniofacial duplication or diprosopus is a very rare malformation that is present in approximately 0.4% of conjoined twins. Here is presented a case of craniofacial duplication in association with bilateral cleft lip/palate in both heads found in a ceramic representation from the early Chimú culture from Peru. A comparative analysis is made with a current case of a 28-week-old fetus with similar characteristics. After reviewing the medical literature on conjoined twins, very few reports of facial cleft in both twins were found, with no reports at all of bilateral cleft lip/palate. This ceramic crock is considered one of the first representations suggestive of craniofacial duplication, and probably the first reporting it in association with facial cleft.

Dental and Nondental Stem Cell Based Regeneration of the Craniofacial Region: A Tissue Based Approach

PubMed Central

Hughes, Declan; Song, Bing

2016-01-01

Craniofacial reconstruction may be a necessary treatment for those who have been affected by trauma, disease, or pathological developmental conditions. The use of stem cell therapy and tissue engineering shows massive potential as a future treatment modality. Currently in the literature, there is a wide variety of published experimental studies utilising the different stem cell types available and the plethora of available scaffold materials. This review investigates different stem cell sources and their unique characteristics to suggest an ideal cell source for regeneration of individual craniofacial tissues. At present, understanding and clinical applications of stem cell therapy remain in their infancy with numerous challenges to overcome. In spite of this, the field displays immense capacity and will no doubt be utilised in future clinical treatments of craniofacial regeneration. PMID:27143979

Oral and Craniofacial Clinical Signs Associated to Genetic Conditions in Human Identification Part I: A Review

PubMed Central

Ayoub, Fouad; Aoun, Nicole; el Husseini, Hassan; Jassar, Houssam; Sayah, Fida; Salameh, Ziad

2015-01-01

Background: Forensic dentistry is one of the most reliable methods used in human identification when other technique as fingerprint, DNA, visual identification cannot be used. Genetic disorders have several manifestations that can target the intra-oral cavity, the cranio-facial area or any location in the human body. Materials and Methods: A literature search of the scientific database (Medline and Science Direct) for the years 1990 to 2014 was carried out to find out all the available papers that indicate oral, cranio-facial signs, genetic and human identification. Results: A table with 10 genetic conditions was described with oral and cranio-facial signs that can help forensic specialist in human identification. Conclusion: This review showed a correlation between genetics, facial and intra-oral signs that would help forensic ondontologist in the identification procedures. PMID:26028912

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

PubMed

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

2014-01-01

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

Management options of non-syndromic sagittal craniosynostosis.

PubMed

Lee, Bryan S; Hwang, Lee S; Doumit, Gaby D; Wooley, Joseph; Papay, Francis A; Luciano, Mark G; Recinos, Violette M

2017-05-01

There have been various effective surgical procedures for the treatment of non-syndromic sagittal craniosynostosis, but no definitive guidelines for management have been established. We conducted a study to elucidate the current state of practice and establish a warranted standard of care. An Internet-based study was sent to 180 pediatric neurosurgeons across the country and 102 craniofacial plastic surgeons in fourteen different countries, to collect data for primary indication for surgical management, preference for timing and choice of surgery, and pre-, peri-, and post-operative management options. The overall response rate from both groups was 32% (n=90/284). Skull deformity was the primary indication for surgical treatment in patients without signs of hydrocephalus for both neurosurgeons and craniofacial surgeons (80% and 63%, respectively). Open surgical management was most commonly performed at six months of age by neurosurgeons (46%) and also by craniofacial surgeons (35%). Open surgical approach was favored for patients younger than four months of age by neurosurgeons (50%), but endoscopic approach was favored by craniofacial surgeons (35%). When performing an open surgical intervention, most neurosurgeons preferred pi or reversed pi procedure (27%), whereas total cranial vault remodeling was the most commonly performed procedure by craniofacial surgeons (37%). The data demonstrated a discrepancy in the treatment options for non-syndromic sagittal craniosynostosis. By conducting/comparing a wide survey to collect consolidative data from both groups of pediatric neurosurgeons and craniofacial plastic surgeons, we can attempt to facilitate the establishment of standard of care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reproduction, embryonic development, and maternal transfer of contaminants in the amphibian Gastrophryne carolinensis.

PubMed

Hopkins, William Alexander; DuRant, Sarah Elizabeth; Staub, Brandon Patrick; Rowe, Christopher Lee; Jackson, Brian Phillip

2006-05-01

Although many amphibian populations around the world are declining at alarming rates, the cause of most declines remains unknown. Environmental contamination is one of several factors implicated in declines and may have particularly important effects on sensitive developmental stages. Despite the severe effects of maternal transfer of contaminants on early development in other vertebrate lineages, no studies have examined the effects of maternal transfer of contaminants on reproduction or development in amphibians. We examined maternal transfer of contaminants in eastern narrow-mouth toads (Gastrophryne carolinensis) collected from a reference site and near a coal-burning power plant. Adult toads inhabiting the industrial area transferred significant quantities of selenium and strontium to their eggs, but Se concentrations were most notable (up to 100 microg/g dry mass). Compared with the reference site, hatching success was reduced by 11% in clutches from the contaminated site. In surviving larvae, the frequency of developmental abnormalities and abnormal swimming was 55-58% higher in the contaminated site relative to the reference site. Craniofacial abnormalities were nearly an order of magnitude more prevalent in hatchlings from the contaminated site. When all developmental criteria were considered collectively, offspring from the contaminated site experienced 19% lower viability. Although there was no statistical relationship between the concentration of Se or Sr transferred to eggs and any measure of offspring viability, our study demonstrates that maternal transfer may be an important route of contaminant exposure in amphibians that has been overlooked.

Reproduction, Embryonic Development, and Maternal Transfer of Contaminants in the Amphibian Gastrophryne carolinensis

PubMed Central

Hopkins, William Alexander; DuRant, Sarah Elizabeth; Staub, Brandon Patrick; Rowe, Christopher Lee; Jackson, Brian Phillip

2006-01-01

Although many amphibian populations around the world are declining at alarming rates, the cause of most declines remains unknown. Environmental contamination is one of several factors implicated in declines and may have particularly important effects on sensitive developmental stages. Despite the severe effects of maternal transfer of contaminants on early development in other vertebrate lineages, no studies have examined the effects of maternal transfer of contaminants on reproduction or development in amphibians. We examined maternal transfer of contaminants in eastern narrow-mouth toads (Gastrophryne carolinensis) collected from a reference site and near a coal-burning power plant. Adult toads inhabiting the industrial area transferred significant quantities of selenium and strontium to their eggs, but Se concentrations were most notable (up to 100 μg/g dry mass). Compared with the reference site, hatching success was reduced by 11% in clutches from the contaminated site. In surviving larvae, the frequency of developmental abnormalities and abnormal swimming was 55–58% higher in the contaminated site relative to the reference site. Craniofacial abnormalities were nearly an order of magnitude more prevalent in hatchlings from the contaminated site. When all developmental criteria were considered collectively, offspring from the contaminated site experienced 19% lower viability. Although there was no statistical relationship between the concentration of Se or Sr transferred to eggs and any measure of offspring viability, our study demonstrates that maternal transfer may be an important route of contaminant exposure in amphibians that has been overlooked. PMID:16675417

Segregation of a paternal insertional translocation results in partial 4q monosomy or 4q trisomy in two siblings

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

Hegmann, K.M.; Spikes, A.S.; Orr-Urtreger, A.

A genetics evaluation was requested for a 6-week-old infant with multiple congenital malformations including mild craniofacial anomalies, truncal hypotonia, hypospadias, and a ventriculoseptal defect. Blood obtained for chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome analysis showed a 46,XY, inv ins (3;4)(p21.32;q25q21.2), inv(4)(p15.3q21.2) karyotype. Therefore, the proband`s chromosome 4 was the unbalanced product of this insertional translocation from the father resulting in partial monosomy 4q. Additionally, the derivative 4 had a pericentric inversion which was also seen in the father`s chromosome 4. During genetic counseling, the proband`s 2-year-old brother was evaluated. He was not felt to be abnormal inmore » appearance, but was described as having impulsive behavior. Chromosome analysis on this child revealed 46, XY, der(3) inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in partial trisomy 4q. FISH using two-color {open_quotes}painting{close_quotes} probes for chromosomes 3 and 4 confirmed the G-banded interpretation in this family. The segregation seen in this family resulted in both reciprocal products being observed in the two children, with partial 4q monosomy showing multiple congenital anomalies, and partial 4q trisomy showing very few phenotypic abnormalities. 13 refs., 5 figs.« less

Mouse Models of Rare Craniofacial Disorders.

PubMed

Achilleos, Annita; Trainor, Paul A

2015-01-01

A rare disease is defined as a condition that affects less than 1 in 2000 individuals. Currently more than 7000 rare diseases have been documented, and most are thought to be of genetic origin. Rare diseases primarily affect children, and congenital craniofacial syndromes and disorders constitute a significant proportion of rare diseases, with over 700 having been described to date. Modeling craniofacial disorders in animal models has been instrumental in uncovering the etiology and pathogenesis of numerous conditions and in some cases has even led to potential therapeutic avenues for their prevention. In this chapter, we focus primarily on two general classes of rare disorders, ribosomopathies and ciliopathies, and the surprising finding that the disruption of fundamental, global processes can result in tissue-specific craniofacial defects. In addition, we discuss recent advances in understanding the pathogenesis of an extremely rare and specific craniofacial condition known as syngnathia, based on the first mouse models for this condition. Approximately 1% of all babies are born with a minor or major developmental anomaly, and individuals suffering from rare diseases deserve the same quality of treatment and care and attention to their disease as other patients. © 2015 Elsevier Inc. All rights reserved.

Bone Repair Cells for Craniofacial Regeneration

PubMed Central

Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

2012-01-01

Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

[Anterior craniofacial resection: oncologic outcome and complications in a series of 111 cases].

PubMed

Suárez, C; Llorente, J L; Fernández de León, R; Cabanillas, R; Suárez, V; López, A

2004-01-01

Anterior craniofacial resection is a standardized procedure for the treatment of ethmoid and frontal orbital tumors with intracranial invasion. A retrospective review of 111 patients with sinonasal tumors involving the anterior skull base who underwent combined craniofacial surgery. The most frequent pathological entity was adenocarcinoma (54 cases) and other epithelial tumors (29 cases). Five year actuarial survival according to the Kaplan-Meier method was 40%. Survival was affected by the histology of the tumor, brain involvement, and deep soft tissue involvement of the orbit. The UICC staging system did not show statistical prognostic significance. Complications occurred in 39 (35.1%) patients, resulting in 4 (3.6%) postoperative deaths. Major complications included cerebrospinal fluid leak in 18 patients, meningitis in 10, infection in 9, stroke in 4, and pneumocephalus in 4. The extent of the craniofacial resection was the most important factor associated with major complications. Despite the advanced stage of most of the patients, anterior craniofacial resection succeeded in terms of an acceptable survival rate. Nevertheless, significant complications were observed although in most patients were not life-threatening and had no negative impact on the quality of life.

Bone Grafting the Cleft Maxilla

MedlinePlus

... of Publications Last Updated: Oct 25, 2007 American Cleft Palate-Craniofacial Association 1504 East Franklin Street, Suite 102 ... order bottles Order ACPA publications © Copyright 2017 American Cleft Palate-Craniofacial Association. Website by Mixer Creative Follow us ...

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.

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

Differences in Craniofacial Structures and Obesity in Caucasian and Chinese Patients with Obstructive Sleep Apnea

PubMed Central

Lee, Richard W. W.; Vasudavan, Sivabalan; Hui, David S.; Prvan, Tania; Petocz, Peter; Darendeliler, M. Ali; Cistulli, Peter A.

2010-01-01

Study Objectives: To explore differences in craniofacial structures and obesity between Caucasian and Chinese patients with obstructive sleep apnea (OSA). Design: Inter-ethnic comparison study. Setting: Two sleep disorder clinics in Australia and Hong Kong. Patients: 150 patients with OSA (74 Caucasian, 76 Chinese). Interventions: Anthropometry, cephalometry, and polysomnography were performed and compared. Subgroup analyses after matching for: (1) body mass index (BMI); (2) OSA severity. Measurements and Results: The mean age and BMI were similar between the ethnic groups. Chinese patients had more severe OSA (AHI 35.3 vs 25.2 events/h, P = 0.005). They also had more craniofacial bony restriction, including a shorter cranial base (63.6 ± 3.3 vs 77.5 ± 6.7 mm, P < 0.001), maxilla (50.7 ± 3.7 vs 58.8 ± 4.3 mm, P < 0.001) and mandible length (65.4 ± 4.2 vs 77.9 ± 9.4 mm, P < 0.001). These findings remained after correction for differences in body height. Similar results were shown in the BMI-matched analysis (n = 66). When matched for OSA severity (n = 52), Chinese patients had more craniofacial bony restriction, but Caucasian patients were more overweight (BMI 30.7 vs 28.4 kg/m2, P = 0.03) and had a larger neck circumference (40.8 vs 39.1 cm, P = 0.004); however, the ratios of BMI to the mandible or maxilla size were similar. Conclusions: Craniofacial factors and obesity contribute differentially to OSA in Caucasian and Chinese patients. For the same degree of OSA severity, Caucasians were more overweight, whereas Chinese exhibited more craniofacial bony restriction. Citation: Lee RWW; Vasudavan S; Hui DS; Prvan T; Petocz P; Darendeliler MA; Cistulli PA. Differences in craniofacial structures and obesity in Caucasian and Chinese patients with obstructive sleep apnea. SLEEP 2010;33(8):1075-1080. PMID:20815189

Further delineation of the SATB2 phenotype

PubMed Central

Döcker, Dennis; Schubach, Max; Menzel, Moritz; Munz, Marita; Spaich, Christiane; Biskup, Saskia; Bartholdi, Deborah

2014-01-01

SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex. In humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2 haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and intellectual disability (ID). A single patient carrying a nonsense mutation in SATB2 has been described to date. In this study, we performed trio-exome sequencing in a 3-year-old girl with CP and severely delayed speech development, and her unaffected parents. Previously, the girl had undergone conventional and molecular karyotyping (microarray analysis), as well as targeted analysis for different diseases associated with developmental delay, including Angelman syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be established. Exome sequencing revealed a de novo nonsense mutation in the SATB2 gene (c.715C>T; p.R239*). The identification of a second patient carrying a de novo nonsense mutation in SATB2 confirms that this gene is essential for normal craniofacial patterning and cognitive development. Based on our data and the literature published so far, we propose a new clinically recognizable syndrome – the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and should be considered in children with ID, severe speech delay, cleft or high-arched palate and abnormal dentition with crowded and irregularly shaped teeth. PMID:24301056

Obstetric significance of fetal craniofacial duplication. A case report.

PubMed

Chervenak, F A; Pinto, M M; Heller, C I; Norooz, H

1985-01-01

Craniofacial duplication (diprosopus) is a rare form of conjoined twins. Whenever fetal hydrocephalus is diagnosed, a careful search for other anomalies, such as diprosopus, is mandatory. The obstetric management depends upon the time of the diagnosis.

77 FR 35990 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... Craniofacial Research Special Emphasis Panel; Molecular Characterization of Salivary Tumors RFA: R01 and R21...: Jayalakshmi Raman, Ph.D., Scientific Review Officer, Scientific Review Branch, National Institute of Dental...

Clinical application of three-dimensional printing technology in craniofacial plastic surgery.

PubMed

Choi, Jong Woo; Kim, Namkug

2015-05-01

Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models.

The craniofacial complex in 47, XXX females.

PubMed

Krusinskiene, Viktorija; Krusinskie, Viktorija; Alvesalo, Lassi; Sidlauskas, Antanas

2005-08-01

A study of the craniofacial complex in four 47, XXX Finnish females, or females with an extra X chromosome, was carried out using cephalometric analysis comprising linear and angular measurements. The lengths of the anterior and posterior cranial bases, the calvarium, mandibular ramus and posterior and upper anterior face heights were found to be significantly shorter than in female controls, while the angles between the foraminal and clival planes, the mandibular plane and cranial base, the maxillary and occlusal planes, the maxillary and mandibular planes and the foraminal and mandibular planes, and also the gonial angle, were significantly enlarged. The present findings of reduced linear measurements, together with the results of studies on the craniofacial complex of 47, XXY and 47, XYY males, suggest dimensional variation between these groups from the promoting effect of an extra Y chromosome and the retarding effect of an extra X chromosome on craniofacial growth.

Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation

PubMed Central

Kong, Yawei; Grimaldi, Michael; Curtin, Eugene; Dougherty, Max; Kaufman, Charles; White, Richard M.; Zon, Leonard I.; Liao, Eric C.

2015-01-01

Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor TRIM abrogated first pharyngeal arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with over-expression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complimentary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation and convergence during craniofacial morphogenesis. PMID:24684905

Clinical Application of Three-Dimensional Printing Technology in Craniofacial Plastic Surgery

PubMed Central

Kim, Namkug

2015-01-01

Three-dimensional (3D) printing has been particularly widely adopted in medical fields. Application of the 3D printing technique has even been extended to bio-cell printing for 3D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts. Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3D printing concept. Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing. To investigate the current status of 3D printing technology and its clinical application, a systematic review of the literature was conducted. In addition, the benefits and possibilities of the clinical application of 3D printing in craniofacial surgery are reviewed, based on personal experiences with more than 500 craniofacial cases conducted using 3D printing tactile prototype models. PMID:26015880

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

PubMed Central

Adams, Dany Spencer; Uzel, Sebastien G. M.; Akagi, Jin; Wlodkowic, Donald; Andreeva, Viktoria; Yelick, Pamela Crotty; Devitt‐Lee, Adrian; Pare, Jean‐Francois; Levin, Michael

2016-01-01

Key points Xenopus laevis craniofacial development is a good system for the study of Andersen–Tawil Syndrome (ATS)‐associated craniofacial anomalies (CFAs) because (1) Kcnj2 is expressed in the nascent face; (2) molecular‐genetic and biophysical techniques are available for the study of ion‐dependent signalling during craniofacial morphogenesis; (3) as in humans, expression of variant Kcnj2 forms in embryos causes a muscle phenotype; and (4) variant forms of Kcnj2 found in human patients, when injected into frog embryos, cause CFAs in the same cell lineages.Forced expression of WT or variant Kcnj2 changes the normal pattern of V mem (resting potential) regionalization found in the ectoderm of neurulating embryos, and changes the normal pattern of expression of ten different genetic regulators of craniofacial development, including markers of cranial neural crest and of placodes.Expression of other potassium channels and two different light‐activated channels, all of which have an effect on V mem, causes CFAs like those induced by injection of Kcnj2 variants. In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an inactive Cl− channel, do not cause CFAs, demonstrating that correct craniofacial development depends on a pattern of bioelectric states, not on ion‐ or channel‐specific signalling.Using optogenetics to control both the location and the timing of ion flux in developing embryos, we show that affecting V mem of the ectoderm and no other cell layers is sufficient to cause CFAs, but only during early neurula stages. Changes in V mem induced late in neurulation do not affect craniofacial development.We interpret these data as strong evidence, consistent with our hypothesis, that ATS‐associated CFAs are caused by the effect of variant Kcnj2 on the V mem of ectodermal cells of the developing face. We predict that the critical time is early during neurulation, and the critical cells are the ectodermal cranial neural crest and placode lineages. This points to the potential utility of extant, ion flux‐modifying drugs as treatments to prevent CFAs associated with channelopathies such as ATS. Abstract Variants in potassium channel KCNJ2 cause Andersen–Tawil Syndrome (ATS); the induced craniofacial anomalies (CFAs) are entirely unexplained. We show that KCNJ2 is expressed in Xenopus and mouse during the earliest stages of craniofacial development. Misexpression in Xenopus of KCNJ2 carrying ATS‐associated mutations causes CFAs in the same structures affected in humans, changes the normal pattern of membrane voltage potential regionalization in the developing face and disrupts expression of important craniofacial patterning genes, revealing the endogenous control of craniofacial patterning by bioelectric cell states. By altering cells’ resting potentials using other ion translocators, we show that a change in ectodermal voltage, not tied to a specific protein or ion, is sufficient to cause CFAs. By adapting optogenetics for use in non‐neural cells in embryos, we show that developmentally patterned K+ flux is required for correct regionalization of the resting potentials and for establishment of endogenous early gene expression domains in the anterior ectoderm, and that variants in KCNJ2 disrupt this regionalization, leading to the CFAs seen in ATS patients. PMID:26864374

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2014-01-01

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

Pediatric craniofacial fractures due to violence: comparing violent and nonviolent mechanisms of injury.

PubMed

Mericli, Alexander F; DeCesare, Gary E; Zuckerbraun, Noel S; Kurland, Kristen S; Grunwaldt, Lorelei; Vecchione, Lisa; Losee, Joseph E

2011-07-01

This study examines the epidemiologic data of pediatric craniofacial fractures secondary to violence, comparing these data to craniofacial fractures sustained from all other causes. A retrospective review was completed on all patients who presented to the emergency department of a major urban children's hospital from 2000 to 2005 with a craniofacial fracture. Data were compared between patients with fractures due to violent and nonviolent mechanisms. Socioeconomic analysis was performed using Geographic Information System mapping and 2000 US Census data by postal code. One thousand five hundred twenty-eight patients were diagnosed with skull and/or facial fractures. Isolated skull fractures were excluded, leaving 793 patients in the study. Ninety-eight children were injured due to violence, and 695 were injured from a nonviolent cause. Patients with violence-related fractures were more likely to be older, male, and nonwhite and live in a socioeconomically depressed area. A greater number of patients with violence-related injuries sustained nasal and mandible angle fractures, whereas more patients with non-violence-related injuries sustained skull and orbital fractures. Those with violence-related craniofacial fractures had a lower percentage of associated multiorgan system injuries and a lower rate of hospital admissions and intensive care unit admissions. The rate of open reduction and internal fixation for craniofacial fractures was similar in both groups. Patients with violence-related fractures had fewer associated serious injuries and lower morbidity and lived in a more socioeconomically depressed area. The information gained from this descriptive study improves our ability to characterize this population of pediatric patients and to identify the associated constellation of injuries in such fractures.

Psychological and Social Factors in Undergoing Reconstructive Surgery Among Individuals With Craniofacial Conditions: An Exploratory Study

PubMed Central

Bemmels, Heather; Biesecker, Barbara; Schmidt, Johanna L.; Krokosky, Alyson; Guidotti, Rick; Sutton, Erica J.

2012-01-01

Objective Reconstructive surgery to improve psychological well-being is commonly offered to children with craniofacial conditions. Few studies have explored the challenges of reconstructive surgery beyond the physical risks: poor treatment outcomes, infection, brain damage, and death. This qualitative study aims to understand the psychological and social implications such interventions can have for individuals with craniofacial conditions. Design A total of 38 individuals between the ages of 12 and 61 with such craniofacial conditions as Sturge-Weber syndrome, Treacher Collins syndrome, Möbius syndrome, cleft lip and palate, Noonan syndrome, Crouzon syndrome, and amniotic band syndrome participated in semistructured video-recorded interviews. Participants were recruited at conferences, through study flyers, and by word of mouth. Descriptive, thematic analysis was used to identify themes related to reconstructive surgery. Results Dominant themes included undergoing surgery to reduce stigmatization, the psychological and social implications of the interventions, outcome satisfaction, parental involvement in decision making about surgery, and recommendations for parents considering surgery for their children with craniofacial conditions. Experiences with reconstructive surgery varied, with some participants expressing surgical benefits and others, disillusionment. Conclusions The range of participant attitudes and experiences reflect the complexity of reconstructive surgery. Pediatric health care teams involved in the care of children with craniofacial conditions play an important role in advising patients (and their parents) about existing treatment options. The psychological and social implications of reconstructive surgery should be relayed to help families weigh the risks and benefits of surgery in an informed and meaningful way. PMID:22315960

Growth hormone positive effects on craniofacial complex in Turner syndrome.

PubMed

Juloski, Jovana; Dumančić, Jelena; Šćepan, Ivana; Lauc, Tomislav; Milašin, Jelena; Kaić, Zvonimir; Dumić, Miroslav; Babić, Marko

2016-11-01

Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features. Copyright © 2016 Elsevier Ltd. All rights reserved.

Craniofacial duplication (diprosopus): report of a case with a review of the literature.

PubMed

Amr, S S; Hammouri, M F

1995-01-01

A case of craniofacial duplication (diprosopus) is presented. Details on this rare form of conjoined twins are described, and the proposed theories of its embryogenesis are discussed with brief review of the pertinent literature.

Surgical Treatment of Pediatric Craniofacial Fractures: A National Perspective.

PubMed

Massenburg, Benjamin B; Sanati-Mehrizy, Paymon; Taub, Peter J

2015-11-01

Head trauma is the most common cause of death because of injury in children, and trauma alone is the leading cause of morbidity and mortality in pediatrics. This study aimed to characterize the demographics and economic burden associated with the surgical and nonsurgical repair of craniofacial fractures in the pediatric inpatient population in the United States. A retrospective cohort study was performed using the 2012 Kids' Inpatient Database which identified 20,070 patients who had a skull or facial fracture, of whom 6395 (31.9%) were treated surgically. Epidemiologic patient and hospital data were analyzed as potential determinants of surgical treatment, prolonged hospitalizations, and higher charges. Pediatric craniofacial fractures are estimated to represent $1.2 billion of national healthcare expenditures annually. The average patient charge for surgical treatment of a craniofacial fracture in the pediatric population is $84,849 compared with $52,490 for nonsurgical management (P < 0.001), and the average length of stay was longer for surgical repair when compared with nonsurgical management for craniofacial fractures (5.3 days versus 4.6 days, P < 0.001). Patients who were older, African American, had nonprivate insurance, whose fracture was caused by external trauma, and who were treated in an urban hospital had an independently increased likelihood of surgical repair of craniofacial fractures. Patients who were older, female, insured, of lower income brackets, whose fracture was caused by a motor vehicle accident, who had surgical treatment of their craniofacial fracture, and who were treated in hospitals in the South, Midwest, or West, teaching hospitals, and government-owned hospitals had an independent risk for a prolonged hospitalization. Patients who were older, Caucasian, insured, whose fracture was caused by a motor vehicle accident, and who were treated in hospitals in the South, teaching hospitals, pediatric hospitals, larger hospitals, and government-owned hospitals had an independent risk for increased patient charges. Craniofacial fractures in the pediatric population represent a large economic burden to the patient and family, as well as the healthcare system as a whole. The identified patient and hospital demographics that are associated with prolonged hospital stays and higher patient charges may represent potential barriers to care, and additional research to elucidate these factors is warranted.

EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

EPA Science Inventory

Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

... Craniofacial Research Special Emphasis Panel; Teleconference Review of Pre Clinical (R34) and Secondary Data Analysis (R03) Applications. Dates: October 18, 2011. Time: 11 a.m. to 1 p.m. Agenda: To review and...

Craniofacial Reconstruction Using Rational Cubic Ball Curves

PubMed Central

Majeed, Abdul; Mt Piah, Abd Rahni; Gobithaasan, R. U.; Yahya, Zainor Ridzuan

2015-01-01

This paper proposes the reconstruction of craniofacial fracture using rational cubic Ball curve. The idea of choosing Ball curve is based on its robustness of computing efficiency over Bezier curve. The main steps are conversion of Digital Imaging and Communications in Medicine (Dicom) images to binary images, boundary extraction and corner point detection, Ball curve fitting with genetic algorithm and final solution conversion to Dicom format. The last section illustrates a real case of craniofacial reconstruction using the proposed method which clearly indicates the applicability of this method. A Graphical User Interface (GUI) has also been developed for practical application. PMID:25880632

A personal tribute to a great educator: how Henry Kawamoto influenced my interest in facial soft tissue anatomy and changed my plastic surgery career.

PubMed

Stuzin, James M

2012-11-01

Henry Kawamoto remains one of the most influential craniofacial surgeons of the 20th century. A Tessier-trained craniofacial surgeon, Dr. Kawamoto has personally influenced not only the lives of his patients, but significantly also the lives of those craniofacial fellows he educated, passing on the Tessier methodology to future generations. This article serves as an anecdote as to how Dr. Kawamoto's mentoring influenced a personal understanding of facial soft tissue anatomy, leading to improved technical approaches for surgical rejuvenation of the aging face.

Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

PubMed

Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

2017-09-01

The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

Normalized Shape and Location of Perturbed Craniofacial Structures in the Xenopus Tadpole Reveal an Innate Ability to Achieve Correct Morphology

PubMed Central

Vandenberg, Laura N.; Adams, Dany S.; Levin, Michael

2012-01-01

Background Embryonic development can often adjust its morphogenetic processes to counteract external perturbation. The existence of self-monitoring responses during pattern formation is of considerable importance to the biomedicine of birth defects, but has not been quantitatively addressed. To understand the computational capabilities of biological tissues in a molecularly-tractable model system, we induced craniofacial defects in Xenopus embryos, then tracked tadpoles with craniofacial deformities and used geometric morphometric techniques to characterize changes in the shape and position of the craniofacial structures. Results Canonical variate analysis revealed that the shapes and relative positions of perturbed jaws and branchial arches were corrected during the first few months of tadpole development. Analysis of the relative movements of the anterior-most structures indicates that misplaced structures move along the anterior-posterior and left-right axes in ways that are significantly different from their normal movements. Conclusions Our data suggest a model in which craniofacial structures utilize a measuring mechanism to assess and adjust their location relative to other local organs. Understanding the correction mechanisms at work in this system could lead to the better understanding of the adaptive decision-making capabilities of living tissues and suggest new approaches to correct birth defects in humans. PMID:22411736

Bilateral lambdoid and sagittal synostosis (BLSS): a unique craniosynostosis syndrome or predictable craniofacial phenotype?

PubMed

Hing, Anne V; Click, Eleanor S; Holder, Ursula; Seto, Marianne L; Vessey, Kyle; Gruss, Joseph; Hopper, Richard; Cunningham, Michael L

2009-05-01

Multisutural craniosynostosis that includes bilateral lambdoid and sagittal synostosis (BLSS) results in a very characteristic head shape with frontal bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and inferior displacement of the ears. This entity has been reported both in the genetics literature as craniofacial dyssynostosis and in the surgical literature as "Mercedes Benz" syndrome. Craniofacial dyssynostosis was first described in 1976 by Dr. Neuhauser when he presented a series of seven patients with synostosis of the sagittal and lambdoid sutures, short stature, and developmental delay. Over the past 30 years nine additional patients with craniofacial dyssynostosis have been reported in the literature adding to the growing evidence for a distinct craniosynostosis syndrome. The term "Mercedes Benz" syndrome was coined by Moore et al. in 1998 due to the characteristic appearance of the fused sutures on three-dimensional CT imaging. In contrast to the aforementioned reported cases of craniofacial dyssynostosis, all three patients had normal development. Recently, there have been several case reports of patients with BLSS and distinct chromosomal anomalies. These findings suggest that BLSS is a heterogeneous disorder perhaps with syndromic, chromosomal, and isolated forms. In this manuscript we will present the largest series of patients with BLSS and review clinical, CT, and molecular findings.

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.

Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

PubMed

Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

2007-07-01

To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

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

PubMed

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

2017-04-01

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

Craniofacial and dental manifestations of triple X syndrome associated with congenital hypothyroidism: a case report.

PubMed

Ferrazzo, Kívia Linhares; Payeras, Marcia Rodrigues; Ferrazzo, Vilmar Antonio; Mezomo, Maurício Barbieri

2014-01-01

Triple X syndrome (47,XXX) is a numerical chromosomal alteration that affects 1/1,000 women, in which the woman is born with an extra X chromosome. Some oral changes have been reported in the literature, as hypodontia, influence on deposition of crown enamel and discrepancies in cephalometric measurements. Other systemic complications may lead to oral abnormalities similar to those seen in triple X patients, such as congenital hypothyroidism (CH). This paper reports a triple X syndrome case associated with CH later treated. Besides delay in cognitive and intellectual development, the patient had changes in teeth development and in cephalometric measurements with deficiencies in the maxilla and mandible. This is the first report of a triple X syndrome associated with CH. Both conditions may result in changes in dentofacial development. © 2013 Special Care Dentistry Association and Wiley Periodicals, Inc.

Recent developments in neurofibromatoses and RASopathies: management, diagnosis and current and future therapeutic avenues.

PubMed

Rauen, Katherine A; Huson, Susan M; Burkitt-Wright, Emma; Evans, D Gareth; Farschtschi, Said; Ferner, Rosalie E; Gutmann, David H; Hanemann, C Oliver; Kerr, Bronwyn; Legius, Eric; Parada, Luis F; Patton, Michael; Peltonen, Juha; Ratner, Nancy; Riccardi, Vincent M; van der Vaart, Thijs; Vikkula, Miikka; Viskochil, David H; Zenker, Martin; Upadhyaya, Meena

2015-01-01

Neurofibromatosis type 1 (NF1) was the first RASopathy and is now one of many RASopathies that are caused by germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Their common underlying pathogenetic etiology causes significant overlap in phenotypic features which includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium "Recent Developments in Neurofibromatoses (NF) and RASopathies: Management, Diagnosis and Current and Future Therapeutic Avenues" chronicle this timely and topical clinical translational research symposium. The overarching goal was to bring together clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and individuals with Ras pathway syndromes to discuss the most state-of-the-art basic science and clinical issues in an effort to spark collaborations directed towards the best practices and therapies for individuals with RASopathies. © 2014 Wiley Periodicals, Inc.

Recent Developments in Neurofibromatoses and RASopathies: Management, Diagnosis and Current and Future Therapeutic Avenues

PubMed Central

Rauen, Katherine A.; Huson, Susan M.; Burkitt-Wright, Emma; Evans, D Gareth; Farschtschi, Said; Ferner, Rosalie E; Gutmann, David H.; Hanemann, C Oliver; Kerr, Bronwyn; Legius, Eric; Parada, Luis F; Patton, Michael; Peltonen, Juha; Ratner, Nancy; Riccardi, Vincent M.; van der Vaart, Thijs; Vikkula, Miikka; Viskochil, David H.; Zenker, Martin; Upadhyaya, Meena

2014-01-01

Neurofibromatosis type 1 was the first RASopathy and is now one of many RASopathies that are caused by germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Their common underlying pathogenetic etiology causes significant overlap in phenotypic features which includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium “Recent Developments in Neurofibromatoses and RASopathies: Management, Diagnosis and Current and Future Therapeutic Avenues” chronicle this timely and topical clinical translational research symposium. The overarching goal was to bring together clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and individuals with Ras pathway syndromes to discuss the most state-of-the-art basic science and clinical issues in an effort to spark collaborations directed towards the best practices and therapies for individuals with RASopathies. PMID:25393061

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

PubMed

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

2016-03-01

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

VERS: a virtual environment for reconstructive surgery planning

NASA Astrophysics Data System (ADS)

Montgomery, Kevin N.

1997-05-01

The virtual environment for reconstructive surgery (VERS) project at the NASA Ames Biocomputation Center is applying virtual reality technology to aid surgeons in planning surgeries. We are working with a craniofacial surgeon at Stanford to assemble and visualize the bone structure of patients requiring reconstructive surgery either through developmental abnormalities or trauma. This project is an extension of our previous work in 3D reconstruction, mesh generation, and immersive visualization. The current VR system, consisting of an SGI Onyx RE2, FakeSpace BOOM and ImmersiveWorkbench, Virtual Technologies CyberGlove and Ascension Technologies tracker, is currently in development and has already been used to visualize defects preoperatively. In the near future it will be used to more fully plan the surgery and compute the projected result to soft tissue structure. This paper presents the work in progress and details the production of a high-performance, collaborative, and networked virtual environment.

Overexpression of esterase D in kidney from trisomy 13 fetuses

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

Loughna, S.; Moore, G.; Gau, G.

1993-10-01

Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D wasmore » found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. 34 refs., 3 figs., 2 tabs.« less

Duplication of (12)(pter-q13.3) combined with deletion of (22)(pter-q11.2) in a patient with features of both chromosome aberrations.

PubMed

Tyshchenko, Nataliya A; Riegel, Mariluce; Evseenkova, Elena G; Zerova, Tatjana E; Gorovenko, Nataliya G; Schinzel, Albert

2007-01-01

We report a patient with multiple dysmorphic signs and congenital malformations, representing a combination of clinical features of duplication (12p) and deletion (22)(q11.2) syndromes. The girl had overgrowth at birth, showed abnormal cranio-facial findings, cleft uvula, a complex conotruncal heart defect, a polycystic right kidney, and an umbilical hernia. She died at the age of 6 months of cardio-respiratory failure. Cytogenetic examination demonstrated a derivative chromosome 12 replacing one of the two chromosomes 22. The paternal karyotype was normal 46,XY while the mother's karyotype was 46,XX,rcp(12;22)(q13.2;q11.2). According to the published data, all patients with deletion 22q11.2 combined with other unbalanced chromosomal aberration have a more severe clinical expression than those with interstitial deletions.

Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.

PubMed

Huang, Christine S; Oberbeck, Nina; Hsiao, Yi-Chun; Liu, Peter; Johnson, Adam R; Dixit, Vishva M; Hymowitz, Sarah G

2018-05-01

Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anterior segment developmental anomalies in a 33-week-old fetus with MIDAS syndrome.

PubMed

Herwig, Martina C; Loeffler, Karin U; Gembruch, Ulrich; Kuchelmeister, Klaus; Müller, Annette M

2014-01-01

We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.

Corresponding morphological and molecular indicators of crude oil toxicity to the developing hearts of mahi mahi

NASA Astrophysics Data System (ADS)

Edmunds, Richard C.; Gill, J. A.; Baldwin, David H.; Linbo, Tiffany L.; French, Barbara L.; Brown, Tanya L.; Esbaugh, Andrew J.; Mager, Edward M.; Stieglitz, John; Hoenig, Ron; Benetti, Daniel; Grosell, Martin; Scholz, Nathaniel L.; Incardona, John P.

2015-12-01

Crude oils from distinct geological sources worldwide are toxic to developing fish hearts. When oil spills occur in fish spawning habitats, natural resource injury assessments often rely on conventional morphometric analyses of heart form and function. The extent to which visible indicators correspond to molecular markers for cardiovascular stress is unknown for pelagic predators from the Gulf of Mexico. Here we exposed mahi (Coryphaena hippurus) embryos to field-collected crude oil samples from the 2010 Deepwater Horizon disaster. We compared visible heart defects (edema, abnormal looping, reduced contractility) to changes in expression of cardiac-specific genes that are diagnostic of heart failure in humans or associated with loss-of-function zebrafish cardiac mutants. Mahi exposed to crude oil during embryogenesis displayed typical symptoms of cardiogenic syndrome as larvae. Contractility, looping, and circulatory defects were evident, but larval mahi did not exhibit downstream craniofacial and body axis abnormalities. A gradation of oil exposures yielded concentration-responsive changes in morphometric and molecular responses, with relative sensitivity being influenced by age. Our findings suggest that 1) morphometric analyses of cardiac function are more sensitive to proximal effects of crude oil-derived chemicals on the developing heart, and 2) molecular indicators reveal a longer-term adverse shift in cardiogenesis trajectory.

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

PubMed Central

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

2013-01-01

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

Investigating alcohol-induced congenital heart defects using optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Gu, Shi; Peterson, Lindsy M.; Ma, Pei; Karunamuni, Ganga; Watanabe, Michiko; Jenkins, Michael W.; Rollins, Andrew M.

2016-03-01

Fetal alcohol syndrome commonly results in neurological and craniofacial defects, additionally, as high as 54% of live-born children with this syndrome also possess cardiac abnormalities. We have previously shown that CNCC-ablated embryos exhibit similar structural and functional phenotypes as ethanol-exposed embryos. Here, we present progress on two fronts toward understanding the association between CNCC dysfunction and FAS-related CHDs. We have developed a technique for measuring the thickness of the cardiac cushions throughout the heart. These values were then mapped onto a surface mesh of the myocardial wall for 3-D visualization. The cushions were observed to be significantly reduced in the outflow tract of CNCC-ablated embryos. We also observed a correlation between abnormal pulsed Doppler waveforms and increased separation of the atrioventricular inferior and superior cushions. This correlation between function and structure will enable rapid phenotyping of perturbed embryos. Finally, we present our preliminary results using methyl donors to rescue ethanol-exposed embryonic CHDs. Betaine was administered along with the ethanol injection to embryos at 21 hours of development. The embryos were then analyzed at day 8 for survival and heart morphology. The administration of betaine resulted in a significant increase in survival and normalization of atrioventricular valve leaflet volume and interventricular septum thickness.

Corresponding morphological and molecular indicators of crude oil toxicity to the developing hearts of mahi mahi

PubMed Central

Edmunds, Richard C.; Gill, J. A.; Baldwin, David H.; Linbo, Tiffany L.; French, Barbara L.; Brown, Tanya L.; Esbaugh, Andrew J.; Mager, Edward M.; Stieglitz, John; Hoenig, Ron; Benetti, Daniel; Grosell, Martin; Scholz, Nathaniel L.; Incardona, John P.

2015-01-01

Crude oils from distinct geological sources worldwide are toxic to developing fish hearts. When oil spills occur in fish spawning habitats, natural resource injury assessments often rely on conventional morphometric analyses of heart form and function. The extent to which visible indicators correspond to molecular markers for cardiovascular stress is unknown for pelagic predators from the Gulf of Mexico. Here we exposed mahi (Coryphaena hippurus) embryos to field-collected crude oil samples from the 2010 Deepwater Horizon disaster. We compared visible heart defects (edema, abnormal looping, reduced contractility) to changes in expression of cardiac-specific genes that are diagnostic of heart failure in humans or associated with loss-of-function zebrafish cardiac mutants. Mahi exposed to crude oil during embryogenesis displayed typical symptoms of cardiogenic syndrome as larvae. Contractility, looping, and circulatory defects were evident, but larval mahi did not exhibit downstream craniofacial and body axis abnormalities. A gradation of oil exposures yielded concentration-responsive changes in morphometric and molecular responses, with relative sensitivity being influenced by age. Our findings suggest that 1) morphometric analyses of cardiac function are more sensitive to proximal effects of crude oil-derived chemicals on the developing heart, and 2) molecular indicators reveal a longer-term adverse shift in cardiogenesis trajectory. PMID:26658479

Syndromal frontonasal dysostosis in a child with a complex translocation involving chromosomes 3, 7, and 11

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

Stevens, C.A.; Qumsiyeh, M.B.

We report on a 4-year-old boy with typical frontonasal dysostosis and an apparently balanced de novo translocation involving chromosomes 3, 7, and 11, and four breakpoints. The karyotype was 46,XY,t(7;3)(3;11) (7pter{r_arrow}7q21.3::3q27{r_arrow}3qter;3pter{r_arrow}3q23::11q21{r_arrow}11qter;11pter{r_arrow}11q21::3q23{r_arrow}3q27::7q21.3{r_arrow}7qter). In situ hybridization with a chromosome 3 painting probe confirmed the interpretation from GTG banding. The child had a widow`s peak, marked hypertelorism, absence of the nasal tip, and widely separated nares. He also had an atrial septal defect, micropenis, small testes, clubfeet, scoliosis, block C2-4, and structural brain abnormalities on MRI. In review we found two other cases of frontonasal dysostosis with chromosome abnormalities, neither of which wasmore » similar to our case. The presence of a de novo (apparently) balanced translocation in our patient may help to locate the gene(s) for frontonasal dysplasia and perhaps other midline craniofacial malformations. 16 refs., 4 figs.« less

Low-dose dasatinib rescues cardiac function in Noonan syndrome

PubMed Central

Yi, Jae-Sung; Huang, Yan; Kwaczala, Andrea T.; Kuo, Ivana Y.; Ehrlich, Barbara E.; Campbell, Stuart G.; Giordano, Frank J.; Bennett, Anton M.

2016-01-01

Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases. We show that the tyrosine kinase inhibitor, dasatinib, at doses orders of magnitude lower than that used for its anticancer activities inhibited PZR tyrosyl phosphorylation in the hearts of NS mice. Low-dose dasatinib treatment of NS mice markedly improved cardiomyocyte contractility and functionality. Remarkably, a low dose of dasatinib reversed the expression levels of molecular markers of cardiomyopathy and reduced cardiac fibrosis in NS and NSML mice. These results suggest that PZR/SHP2 signaling is a common target of both NS and NSML and that low-dose dasatinib may represent a unifying therapy for the treatment of PTPN11-related cardiomyopathies. PMID:27942593

75 FR 58409 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and Craniofacial... Kelly, Scientific Review Officer, Scientific Review Branch, [[Page 58410

Reflections on my journey in biomedical research: the art, science, and politics of advocacy.

PubMed

Slavkin, H C

2013-01-01

Scientific Discovery often reflects the art, science, and advocacy for biomedical research. Here the author reflects on selected highlights of discovery that contributed to several aspects of our understanding of craniofacial biology and craniofacial diseases and disorders.

PATHOGENESIS OF METHANOL-INDUCED CRANIOFACIAL DEFECTS IN C57BL/6J MICE

EPA Science Inventory

BACKGROUND: Methanol administered to C57BL/6J mice during gastrulation causes severe craniofacial dysmorphology. We describe dysmorphogenesis, cell death, cell cycle assessment, and effects on development of cranial ganglia and nerves observed following administration of methanol...

Maternal diet supplementation with methyl donors and increased parity affect the incidence of craniofacial defects in the offspring of twisted gastrulation mutant mice.

PubMed

Billington, Charles J; Schmidt, Brian; Zhang, Lei; Hodges, James S; Georgieff, Michael K; Schotta, Gunnar; Gopalakrishnan, Rajaram; Petryk, Anna

2013-03-01

Diets rich in methyl-donating compounds, including folate, can provide protection against neural tube defects, but their role in preventing craniofacial defects is less clear. Mice deficient in Twisted gastrulation (TWSG1), an extracellular modulator of bone morphogenetic protein signaling, manifest both midline facial defects and jaw defects, allowing study of the effects of methyl donors on various craniofacial defects in an experimentally tractable animal model. The goal of this study was to examine the effects of maternal dietary supplementation with methyl donors on the incidence and type of craniofacial defects among Twsg1(-/-) offspring. Nulliparous and primiparous female mice were fed an NIH31 standard diet (control) or a methyl donor supplemented (MDS) diet (folate, vitamin B-12, betaine, and choline). Observed defects in the pups were divided into those derived mostly from the first branchial arch (BA1) (micrognathia, agnathia, cleft palate) and midline facial defects in the holoprosencephaly spectrum (cyclopia, proboscis, and anterior truncation). In the first pregnancy, offspring of mice fed the MDS diet had lower incidence of BA1-derived defects (12.8% in MDS vs. 32.5% in control; P = 0.02) but similar incidence of midline facial defects (6.4% in MDS vs. 5.2% in control; P = 1.0). Increased maternal parity was independently associated with increased incidence of craniofacial defects after adjusting for diet (from 37.7 to 59.5% in control, P = 0.04 and from 19.1 to 45.3% in MDS, P = 0.045). In conclusion, methyl donor supplementation shows protective effects against jaw defects, but not midline facial defects, and increased parity can be a risk factor for some craniofacial defects.

Children of the Philippines: attitudes toward visible physical impairment.

PubMed

Harper, D C; Peterson, D B

2001-11-01

This pilot study was designed to evaluate children's attitudes and understanding of physical disabilities with special reference to those with craniofacial anomalies in the Philippines. Children with and without craniofacial anomalies were studied. This was a two-group correlational design with additional statistical assessment of subgroup differences. Each group was interviewed and information obtained on a standard disability preference task, attributions for playmate choice, and frequency of contact with disabilities. Parents completed a structured interview. Participants were 122 children recruited from Negros, Philippines. Fifty-four children with craniofacial anomalies (aged 7 to 12 years) were enrolled in the study, and 68 children without any disabilities were recruited from a local school in Bacolod City, Negros, Philippines. Participants completed a picture-ranking interview of specific physical disabilities and provided their reasons for their play choices and their contact with physical disabilities. The Kendall W correlation was significant for the children with craniofacial anomalies and for those without physical disabilities. Both groups reported lower preferences for disabilities that interfere with play and social interactions. Children depicted with facial anomalies received lower preference, compared with other physical disabilities. Children with craniofacial anomalies who have experienced surgical repair reported more positive rankings for the child depicted with a facial cleft. Sex differences in disability preference were noted. Children in the Philippines with and without craniofacial differences revealed similarities in preferences to children in several Western (United States) and non-Western countries. Children depicted with facial anomalies received lower preference than other visible physical differences. Children reported both positive and negative explanations for their disability play preferences. Facial differences may result in illogical and negative explanations for social avoidance among children. Similar reactions are noted in other parts of the world.

Craniofacial resection for nonmelanoma skin cancer of the head and neck.

PubMed

Backous, Douglas D; DeMonte, Franco; El-Naggar, Adel; Wolf, Pat; Weber, Randal S

2005-06-01

We reviewed our experience with craniofacial resection for advanced, nonmelanoma skin cancer of the head and neck to determine prognostic factors, local control rate, disease free survival, morbidity, and mortality. Retrospective review of consecutive patients treated at a tertiary referral center from 1982 to 1993. Charts of patients having craniofacial resection for aggressive nonmelanoma cutaneous malignancies were reviewed and living patients followed for 10 additional years. Demographics, histology, previous interventions, treatment, surgical pathology, reconstructions, and complications were examined. The product-limit method was used to calculate survival functions, and the log-rank test was used to compare survival distributions. Thirty-five patients, mean age 66.7 years, received treatment at our facility. Follow-up ranged from 2 to 191 (mean 47.4) months. Histology included 20 squamous cell carcinomas (SCC) and 15 basal cell carcinomas (BCC). Sixty percent had craniofacial resection alone, and 28.6% also had postoperative radiotherapy. There were two perioperative deaths, and 37.1% suffered early and 14.3% late surgical complications. Two- and five- year survival was significantly better (P=.02) with BCC (92% and 76%) than with SCC (54% and 24%). Long-term disease-specific survival was 20%, and 11.4% of our subjects were living with disease. Intracranial extension (P=.02), perineural invasion (P=.049), and prior radiotherapy significantly decreased 5-year survival. Acceptable mortality and morbidity is possible using craniofacial resection to treat advanced nonmelanoma skin cancer. Although disease-specific survival remains poor, positive trends were noted in local control beginning at 2 years of follow-up. Because patients often have few remaining options for cure, craniofacial resection is justified when technically feasible.

An Anthropometric Study of Cranio-Facial Measurements and Their Correlation with Vertical Dimension of Occlusion among Saudi Arabian Subpopulations.

PubMed

Majeed, Muhammed Irfan; Haralur, Satheesh B; Khan, Muhammed Farhan; Al Ahmari, Maram Awdah; Al Shahrani, Nourah Falah; Shaik, Sharaz

2018-04-15

Determining and restoring physiological vertical dimension of occlusion (VDO) is the critical step during complete mouth rehabilitation. The improper VDO compromises the aesthetics, phonetics and functional efficiency of the prosthesis. Various methods are suggested to determine the accurate VDO, including the facial measurements in the clinical situations with no pre-extraction records. The generalisation of correlation between the facial measurements to VDO is criticised due to gender dimorphism and racial differences. Hence, it is prudent to verify the hypothesis of facial proportion and correlation of lower third of the face to remaining craniofacial measurements in different ethnic groups. The objective of the study was to evaluate the correlation of craniofacial measurements and OVD in the Saudi-Arabian ethnic group. Total of 228 participants from Saudi-Arabian Ethnic group were randomly recruited in this cross-sectional study. Fifteen craniofacial measurements were recorded with modified digital Vernier callipers, and OVD was recorded at centric occlusion. The obtained data were analysed by using the Spearman's correlation and linear regression analysis. The Mean OVD in male participants was higher (69.25 ± 5.54) in comparison to female participants (57.41 ± 5.32). The craniofacial measurement of Exocanthion-right labial commissure and the Mesial wall of the right external auditory canal-orbitale lateral had a strong positive correlation with VDO. The strong correlation was recorded with a trichion-upper border of right eyebrow line and trichion-Nasion only in males. Meanwhile, the length of an auricle recorded the positive correlation in female participants. Being simple and non-invasive technique, craniofacial measurements and linear equations could be routinely utilised to determine VDO.

Academic Productivity of Faculty Associated With Craniofacial Surgery Fellowship Programs.

PubMed

Ruan, Qing Zhao; Ricci, Joseph A; Silvestre, Jason; Ho, Olivia A; Ganor, Oren; Lee, Bernard T

2017-11-01

The H-index is increasingly being used as a measure of academic productivity and has been applied to various surgical disciplines. Here the authors calculate the H-index of craniofacial surgery fellowship faculty in North America in order to determine its utility for academic productivity among craniofacial surgeons. A list of fellowship programs was obtained from the website of the American Society of Craniofacial Surgery. Faculty demographics and institution characteristics were obtained from official program websites and the H-index was calculated using Scopus (Elsevier, USA). Data were assessed using bivariate analysis tools (Kruskal-Wallis and Mann-Whitney tests) to determine the relationship between independent variables and career publications, H-index and 5-year H-index (H5-index) of faculty. Dunn test for multiple comparisons was also calculated. A total of 102 faculty members from 29 craniofacial surgery fellowship programs were identified and included. Faculty demographics reflected a median age of 48 (interquartile range [IQR] 13), a predominantly male sample (88/102, 89.7%), and the rank of assistant professor being the most common among faculty members (41/102, 40.2%). Median of career publications per faculty was 37 (IQR 52.5) and medians of H-index and H5-index were 10.0 (IQR 13.75) and 3.5 (IQR 3.25), respectively. Greater age, male gender, Fellow of the American College of Surgeons membership, higher academic rank, and program affiliation with ranked research medical schools were significantly associated with higher H-indices. Variables associated with seniority were positively associated with the H-index. These results suggest that the H-index may be used as an adjunct in determining academic productivity for promotions among craniofacial surgeons.

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

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2012-09-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and... Review Officer, Scientific Review Branch, National Institute of Dental & Craniofacial Research, National...

Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

PubMed

Arce-Estrada, Gabriel Emmanuel; Gómez-Toscano, Valeria; Cedillo-Peláez, Carlos; Sesman-Bernal, Ana Luisa; Bosch-Canto, Vanessa; Mayorga-Butrón, José Luis; Vargas-Villavicencio, José Antonio; Correa, Dolores

2017-07-03

We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. A two-month-old male had a twin in utero who disappeared between the 7 th and the 14 th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Advances in imaging: impact on studying craniofacial bone structure.

PubMed

Majumdar, S

2003-01-01

Methods for measuring the structure of craniofacial bones are discussed in this paper. In addition to the three-dimensional macro-structure of the craniofacial skeleton, there is considerable interest in imaging the bone at a microscopic resolution in order to depict the micro-architecture of the trabecular bone itself. In addition to the density of the bone, the microarchitecture reflects bone quality. An understanding of bone quality and density changes has implications for a number of craniofacial pathologies, as well as for implant design and understanding the biomechanical function and loading of the jaw. Trabecular bone micro-architecture has been recently imaged using imaging methods such as micro-computed tomography, magnetic resonance imaging, and the images have been used in finite element models to assess bone mechanical properties. In this paper, some of the recent advances in micro-computed tomography and magnetic resonance imaging are reviewed, and their potential for imaging the trabecular bone in mandibular bones is presented. Examples of in vitro and in vivo images are presented.

Craniofacial morphometric analysis of mandibular prognathism.

PubMed

Chang, H P; Liu, P H; Yang, Y H; Lin, H C; Chang, C H

2006-03-01

The purpose of this study was to provide more information about the morphological characteristics of the craniofacial complex in mandibular prognathism. Forty young adult males having mandibular prognathism were compared with 40 having normal occlusion. This was conducted to carry out geometric morphometric assessments to localize alterations, using Procrustes analysis and thin-plate spline analysis, in addition to conventional cephalometric techniques. Procrustes analysis indicated that the mean craniofacial, midfacial and mandibular morphology was significantly different in prognathic subjects compared with normal controls. This finding was corroborated by the multivariate Hotelling T(2)-test of cephalometric variables. Mandibular prognathism demonstrated a shorter and slightly retropositioned maxilla, a greater total length and anterior positioning of the mandible. Thin-plate spline analysis revealed a developmental diminution of the palatomaxillary region anteroposteriorly and a developmental elongation of the mandible anteroposteriorly, leading to the appearance of a prognathic mandibular profile. In conclusion, thin-plate spline analysis seems to provide a valuable supplement for conventional cephalometric analysis because the complex patterns of craniofacial shape change are visualized suggestive by means of grid deformations.

SRF regulates craniofacial development through selective recruitment of MRTF cofactors by PDGF signaling.

PubMed

Vasudevan, Harish N; Soriano, Philippe

2014-11-10

Receptor tyrosine kinase signaling is critical for mammalian craniofacial development, but the key downstream transcriptional effectors remain unknown. We demonstrate that serum response factor (SRF) is induced by both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) signaling in mouse embryonic palatal mesenchyme cells and that Srf neural crest conditional mutants exhibit facial clefting accompanied by proliferation and migration defects. Srf and Pdgfra mutants interact genetically in craniofacial development, but Srf and Fgfr1 mutants do not. This signal specificity is recapitulated at the level of cofactor activation: while both PDGF and FGF target gene promoters show enriched genome-wide overlap with SRF ChIP-seq peaks, PDGF selectively activates a network of MRTF-dependent cytoskeletal genes. Collectively, our results identify a role for SRF in proliferation and migration during craniofacial development and delineate a mechanism of receptor tyrosine kinase specificity mediated through differential cofactor usage, leading to a PDGF-responsive SRF-driven transcriptional program in the midface. Copyright © 2014 Elsevier Inc. All rights reserved.

Surgical Management of Polyostotic Craniofacial Fibrous Dysplasia: Long-Term Outcomes and Predictors for Postoperative Regrowth

PubMed Central

Boyce, Alison M.; Burke, Andrea; Peck, Carolee Cutler; DuFresne, Craig R.; Lee, Janice S.; Collins, Michael T.

2017-01-01

Background The mainstay of treatment for craniofacial fibrous dysplasia is surgical; however, optimal indications and techniques are poorly understood, particularly in polyostotic disease and McCune-Albright syndrome. This study investigated surgical indications and risk factors for recurrence in a large cohort. Methods One hundred thirty-three craniofacial fibrous dysplasia subjects in a natural history study were evaluated. Radiographic studies, operative reports, and clinical records were reviewed. Results Thirty-six subjects underwent 103 craniofacial procedures (mean, 2.8 operations per subject), with 13.5 ± 10.5-year follow-up (range, 0 to 39 years). The most common indication was craniofacial deformity (n = 61 operations), including 36 initial operations (59 percent) and 26 reoperations (41 percent). Mean time to reoperation was 3.4 ± 3.2 years (range, 0.3 to 13.3 years). Re-growth occurred after 42 operations (68 percent), and was more frequent after operations in subjects with McCune-Albright syndrome growth hormone excess [22 of 25 operations (88 percent)] than without growth hormone excess [15 of 36 operations (58 percent); p = 0.02]. Of 11 subjects with growth hormone excess, nine (82 percent) were undiagnosed at the time of their initial operation. Regrowth was more frequent after debulking procedures [31 of 38 (82 percent)] than after more aggressive reconstructions [nine of 20 (45 percent); p = 0.007]. Eleven subjects underwent treatment for aneurysmal bone cysts, with recurrence in one subject. Eleven subjects underwent biopsies and none had complications or regrowth. Conclusions Craniofacial fibrous dysplasia regrowth and reoperation are common, particularly after debulking procedures. Outcomes are favorable for aneurysmal bone cysts and biopsies. McCune-Albright syndrome growth hormone excess is a risk factor for regrowth, and may be underdiagnosed in surgical patients. Surgeons should be aware of appropriate screening for endocrinopathies in fibrous dysplasia. These findings highlight the importance of a multidisciplinary approach to craniofacial fibrous dysplasia, and individualized care with long-term follow-up. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV. PMID:27219238

A PCA-Based method for determining craniofacial relationship and sexual dimorphism of facial shapes.

PubMed

Shui, Wuyang; Zhou, Mingquan; Maddock, Steve; He, Taiping; Wang, Xingce; Deng, Qingqiong

2017-11-01

Previous studies have used principal component analysis (PCA) to investigate the craniofacial relationship, as well as sex determination using facial factors. However, few studies have investigated the extent to which the choice of principal components (PCs) affects the analysis of craniofacial relationship and sexual dimorphism. In this paper, we propose a PCA-based method for visual and quantitative analysis, using 140 samples of 3D heads (70 male and 70 female), produced from computed tomography (CT) images. There are two parts to the method. First, skull and facial landmarks are manually marked to guide the model's registration so that dense corresponding vertices occupy the same relative position in every sample. Statistical shape spaces of the skull and face in dense corresponding vertices are constructed using PCA. Variations in these vertices, captured in every principal component (PC), are visualized to observe shape variability. The correlations of skull- and face-based PC scores are analysed, and linear regression is used to fit the craniofacial relationship. We compute the PC coefficients of a face based on this craniofacial relationship and the PC scores of a skull, and apply the coefficients to estimate a 3D face for the skull. To evaluate the accuracy of the computed craniofacial relationship, the mean and standard deviation of every vertex between the two models are computed, where these models are reconstructed using real PC scores and coefficients. Second, each PC in facial space is analysed for sex determination, for which support vector machines (SVMs) are used. We examined the correlation between PCs and sex, and explored the extent to which the choice of PCs affects the expression of sexual dimorphism. Our results suggest that skull- and face-based PCs can be used to describe the craniofacial relationship and that the accuracy of the method can be improved by using an increased number of face-based PCs. The results show that the accuracy of the sex classification is related to the choice of PCs. The highest sex classification rate is 91.43% using our method. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

PubMed Central

Ohnishi, Tetsuo; Yamada, Kazuo; Watanabe, Akiko; Ohba, Hisako; Sakaguchi, Toru; Honma, Yota; Iwayama, Yoshimi; Toyota, Tomoko; Maekawa, Motoko; Watanabe, Kazutada; Detera-Wadleigh, Sevilla D.; Wakana, Shigeharu; Yoshikawa, Takeo

2011-01-01

Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia. PMID:22242126

An eye on the head: the development and evolution of craniofacial muscles.

PubMed

Sambasivan, Ramkumar; Kuratani, Shigeru; Tajbakhsh, Shahragim

2011-06-01

Skeletal muscles exert diverse functions, enabling both crushing with great force and movement with exquisite precision. A remarkably distinct repertoire of genes and ontological features characterise this tissue, and recent evidence has shown that skeletal muscles of the head, the craniofacial muscles, are evolutionarily, morphologically and molecularly distinct from those of the trunk. Here, we review the molecular basis of craniofacial muscle development and discuss how this process is different to trunk and limb muscle development. Through evolutionary comparisons of primitive chordates (such as amphioxus) and jawless vertebrates (such as lampreys) with jawed vertebrates, we also provide some clues as to how this dichotomy arose.

Craniofacial Duplication: A Case Report

PubMed Central

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-01-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature. PMID:24179933

Craniofacial duplication: a case report.

PubMed

Suryawanshi, Pradeep; Deshpande, Mandar; Verma, Nitin; Mahendrakar, Vivek; Mahendrakar, Sandhya

2013-09-01

A craniofacial duplication or diprosopus is an unusual variant of conjoined twinning. The reported incidence is one in 180,000-15 million births and 35 cases have been reported till date. The phenotype is wide, with the partial duplication of a few facial structures to complete dicephalus. A complete duplication is associated with a high incidence of anomalies in the central nervous system, cardiovascular system, gastrointestinal system and the respiratory system, whereas no major anomalies are found in the infants with a partial duplication. A term baby with the features of a craniofacial duplication has been described, with the proposed theories on embryogenesis and a brief review of the literature.

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An assessment of the compliance of systematic review articles published in craniofacial surgery with the PRISMA statement guidelines: A systematic review.

PubMed

Pidgeon, Thomas Edward; Wellstead, Georgina; Sagoo, Harkiran; Jafree, Daniyal J; Fowler, Alexander J; Agha, Riaz A

2016-10-01

Systematic review evidence is increasing within craniofacial surgery. Compliance with recognised reporting guidelines for systematic review evidence has not been assessed. To assess the compliance of systematic reviews published in craniofacial journals with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting criteria. Thomson Reuters impact factor was used to identify three top craniofacial journals. A search for all systematic review articles published in these journals from 1st May 2010 to 30th April 2015 was conducted using MEDLINE PubMed. Two independent researchers assessed each study for inclusion and performed the data extraction. Data included the article reference information; the pathology and interventions examined and compliance of each review article with the PRISMA checklist. 97 studies were returned by the search. 62 studies proceeded to data extraction. The mean percentage of applicable PRISMA items that were met across all studies was 72.5% (range 28.6-96.2%). The area of poorest compliance was with the declaration of a study protocol (19.4% of studies). Only 37.1% of studies declared their source of funding. Compliance of systematic review articles within craniofacial surgery with areas of the PRISMA checklist could be improved. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The Public Recognizes Plastic Surgeons as Leading Experts in the Treatment of Congenital Cleft and Craniofacial Anomalies.

PubMed

Denadai, Rafael; Samartine Junior, Hugo; Denadai, Rodrigo; Raposo-Amaral, Cassio Eduardo

2015-11-01

The aim of this study is to assess the public perception of plastic surgeons (PS) as craniofacial surgery specialists. Members of the public (N = 1514) were asked to choose 1 or 2 specialists that they perceived to be an expert for 13 craniofacial surgery-related scenarios. Response patterns were distributed as "plastic surgeon alone" (PS alone), "PS combined with other specialists", or "no plastic surgeon" (No PS). Sociodemographic data, previous plastic surgery contact, and source of reported information were also collected. "Plastic surgeon alone" was significantly (all P < 0.05) more recognized as experts than all other response patterns particularly in congenital anomalies-related scenarios (83.33%). There was a significantly (all P < 0.05) poor understanding of the role of PSs in head/neck infection management, chronic facial palsy management, dental disease management, head and neck cancer surgery, vascular malformation surgery, and facial fracture surgery. Sex, age, education level, health care professional, prior plastic surgery contact, and source of reported information were not significant (all P < 0.05) determinants of "PS" as the response in bivariate and multivariate analyses. Public recognized PSs as experts primarily in treatment of congenital cleft and craniofacial anomalies, but as the overall scope of craniofacial surgery practice was poorly understood and known, improved public education is needed.

Application of Computer-Assisted Design and Manufacturing-Fabricated Artificial Bone in the Reconstruction of Craniofacial Bone Defects.

PubMed

Liang, Weiqiang; Yao, Yuanyuan; Huang, Zixian; Chen, Yuhong; Ji, Chenyang; Zhang, Jinming

2016-07-01

The purpose of this study was to evaluate the clinical application of individual craniofacial bone fabrications using computer-assisted design (CAD)-computer-assisted manufacturing technology for the reconstruction of craniofacial bone defects. A total of 8 patients diagnosed with craniofacial bone defects were enrolled in this study between May 2007 and August 2010. After computed tomography scans were obtained, the patients were fitted with artificial bone that was created using CAD software, rapid prototyping technology, and epoxy-methyl acrylate resin and hydroxyapatite materials. The fabrication was fixed to the defect area with titanium screws, and soft tissue defects were repaired if necessary. The fabrications were precisely fixed to the defect areas, and all wounds healed well without any serious complications except for 1 case with intraoral incision dehiscence, which required further treatment. Postoperative curative effects were retrospectively observed after 6 to 48 months, acceptable anatomic and cosmetic outcomes were obtained, and no rejections or other complications occurred. The use of CAD-computer-assisted manufacturing technology-assisted epoxy-methyl acrylate resin and hydroxyapatite composite artificial bone to treat patients with craniofacial bone defects could enable the precise reconstruction of these defects and obtain good anatomic and cosmetic outcomes. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The influence of craniofacial to standing height proportion on perceived attractiveness.

PubMed

Naini, F B; Cobourne, M T; McDonald, F; Donaldson, A N A

2008-10-01

An idealised male image, based on Vitruvian Man, was created. The craniofacial height was altered from a proportion of 1/6 to 1/10 of standing height, creating 10 images shown in random order to 89 observers (74 lay people; 15 clinicians), who ranked the images from the most to the least attractive. The main outcome was the preference ranks of image attractiveness given by the observers. Linear regressions were used to assess what influences the choice for the most and the least attractive images, followed by a multivariate rank ordinal logistic regression to test the influence of age, gender, ethnicity and professional status of the observer. A craniofacial height to standing height proportion of 1/7.5 was perceived as the most attractive (36%), followed by a proportion of 1/8 (26%). The images chosen as most attractive by more than 10% of observers had a mean proportion of 1/7.8(min=1/7; max=1/8.5). The images perceived as most unattractive had a proportion of 1/6 and 1/10. The choice of images was not influenced by the age, gender, ethnicity or professional status of the observers. The ideal craniofacial height to standing height proportion is in the range 1/7 to 1/8.5. This finding should be considered when planning treatment to alter craniofacial or facial height.

Current and emerging basic science concepts in bone biology: implications in craniofacial surgery.

PubMed

Oppenheimer, Adam J; Mesa, John; Buchman, Steven R

2012-01-01

Ongoing research in bone biology has brought cutting-edge technologies into everyday use in craniofacial surgery. Nonetheless, when osseous defects of the craniomaxillofacial skeleton are encountered, autogenous bone grafting remains the criterion standard for reconstruction. Accordingly, the core principles of bone graft physiology continue to be of paramount importance. Bone grafts, however, are not a panacea; donor site morbidity and operative risk are among the limitations of autologous bone graft harvest. Bone graft survival is impaired when irradiation, contamination, and impaired vascularity are encountered. Although the dura can induce calvarial ossification in children younger than 2 years, the repair of critical-size defects in the pediatric population may be hindered by inadequate bone graft donor volume. The novel and emerging field of bone tissue engineering holds great promise as a limitless source of autogenous bone. Three core constituents of bone tissue engineering have been established: scaffolds, signals, and cells. Blood supply is the sine qua non of these components, which are used both individually and concertedly in regenerative craniofacial surgery. The discerning craniofacial surgeon must determine the proper use for these bone graft alternatives, while understanding their concomitant risks. This article presents a review of contemporary and emerging concepts in bone biology and their implications in craniofacial surgery. Current practices, areas of controversy, and near-term future applications are emphasized.

Sh3pxd2b Mice Are a Model for Craniofacial Dysmorphology and Otitis Media

PubMed Central

Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E.; Zheng, Qing Y.

2011-01-01

Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2bnee) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2bnee mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2bnee mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2bnee) mirrors craniofacial dysmorphology and otitis media in humans. PMID:21818352

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

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2012-12-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental..., Bethesda, MD 20892, 301-594-0652, [email protected] . Name of Committee: National Institute of Dental... of Dental & Craniofacial Research, National Institutes of Health, 45 Center Dr. Room 4AN 32J...

78 FR 59708 - National Institute of Dental and Craniofacial Research; Notice of Closed Meeting

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

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2010-02-19

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

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2012-12-17

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

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2011-12-27

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2012-04-19

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78 FR 7794 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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75 FR 62553 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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75 FR 2150 - National Institute of Dental & Craniofacial Research; Notice of Closed Meetings

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2010-01-14

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2011-01-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act.... Krishnaraju, PhD, MS, Scientific Review Officer, Scientific Review Branch, National Inst. of Dental...

Understanding the Anatomic Basis for Obstructive Sleep Apnea Syndrome in Adolescents

PubMed Central

Kim, Christopher; Bagchi, Sheila; Keenan, Brendan T.; Comyn, François-Louis; Wang, Stephen; Tapia, Ignacio E.; Huang, Shirley; Traylor, Joel; Torigian, Drew A.; Bradford, Ruth M.; Marcus, Carole L.

2015-01-01

Rationale: Structural risk factors for obstructive sleep apnea syndrome (OSAS) in adolescents have not been well characterized. Because many adolescents with OSAS are obese, we hypothesized that the anatomic OSAS risk factors would be more similar to those in adults than those in children. Objectives: To investigate the anatomic risk factors in adolescents with OSAS compared with obese and lean control subjects using magnetic resonance imaging (MRI). Methods: Three groups of adolescents (age range: 12–16 yr) underwent MRI: obese individuals with OSAS (n = 49), obese control subjects (n = 38), and lean control subjects (n = 50). Measurements and Main Results: We studied 137 subjects and found that (1) obese adolescents with OSAS had increased adenotonsillar tissue compared with obese and lean control subjects; (2) obese OSAS adolescents had a smaller nasopharyngeal airway than control subjects; (3) the size of other upper airway soft tissue structures (volume of the tongue, parapharyngeal fat pads, lateral walls, and soft palate) was similar between subjects with OSAS and obese control subjects; (4) although there were no major craniofacial abnormalities in most of the adolescents with OSAS, the ratio of soft tissue to craniofacial space surrounding the airway was increased; and (5) there were sex differences in the pattern of lymphoid proliferation. Conclusions: Increased size of the pharyngeal lymphoid tissue, rather than enlargement of the upper airway soft tissue structures, is the primary anatomic risk factor for OSAS in obese adolescents. These results are important for clinical decision making and suggest that adenotonsillectomy should be considered as the initial treatment for OSAS in obese adolescents, a group that has poor continuous positive airway pressure adherence and difficulty in achieving weight loss. PMID:25835282

Juvenile Moyamoya and Craniosynostosis in a Child with Deletion 1p32p31: Expanding the Clinical Spectrum of 1p32p31 Deletion Syndrome and a Review of the Literature

PubMed Central

Prontera, Paolo; Rogaia, Daniela; Mencarelli, Amedea; Ottaviani, Valentina; Guercini, Giorgio; Bersano, Anna; Stangoni, Gabriela

2017-01-01

Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine FOXD3−/− model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA. PMID:28926972

Limb-body wall defect: experience of a reference service of fetal medicine from Southern Brazil.

PubMed

Gazolla, Ana C; da Cunha, André C; Telles, Jorge A B; Betat, Rosilene da S; Romano, Mayara A; Marshall, Isabel; Gobatto, Amanda M; de H Bicca, Anna M; Arcolini, Camila P; Dal Pai, Thaís K V; Vieira, Luciane R; Targa, Luciano V; Betineli, Ildo; Zen, Paulo R G; Rosa, Rafael F M

2014-10-01

Limb-body wall defect is a rare condition characterized by a combination of large and complex defects of the ventral thorax and abdominal wall with craniofacial and limb anomalies. The aim of this study was to describe the experience of our fetal medicine service, a reference from Southern Brazil, with prenatally diagnosed patients with a limb-body wall defect in a 3 years period. Only patients who fulfilled the criteria suggested by Hunter et al. (2011) were included in the study. Clinical data and results of radiological and cytogenetic evaluation were collected from their medical records. Our sample was composed of 8 patients. Many of their mothers were younger than 25 years (50%) and in their first pregnancy (62.5%). It is noteworthy that one patient was referred due to suspected anencephaly and another due to a twin pregnancy with an embryonic sac. Craniofacial defects were verified in three patients (37.5%), thoracic/abdominal abnormalities in 6 (75%) and limb defects in eight (100%). Congenital heart defects were observed in five patients (62.5%). One of them presented a previously undescribed complex heart defect. The results disclosed that complementary exams, such as MRI and echocardiography, are important to better define the observed defects. Some of them, such as congenital heart defects, may be more common than previously reported. This definition is essential for the proper management of the pregnancy and genetic counseling of the family. The birth of these children must be planned with caution and for the prognosis a long survival possibility, despite unlikely and rare, must be considered. © 2014 Wiley Periodicals, Inc.

Comparison of the mouse Embryonic Stem cell Test, the rat Whole Embryo Culture and the Zebrafish Embryotoxicity Test as alternative methods for developmental toxicity testing of six 1,2,4-triazoles

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

Jong, Esther de, E-mail: Esther.de.Jong@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Barenys, Marta

2011-06-01

The relatively high experimental animal use in developmental toxicity testing has stimulated the search for alternatives that are less animal intensive. Three widely studied alternative assays are the mouse Embryonic Stem cell Test (EST), the Zebrafish Embryotoxicity Test (ZET) and the rat postimplantation Whole Embryo Culture (WEC). The goal of this study was to determine their efficacy in assessing the relative developmental toxicity of six 1,2,4-triazole compounds, flusilazole, hexaconazole, cyproconazole, triadimefon, myclobutanil and triticonazole. For this purpose, we analyzed effects and relative potencies of the compounds in and among the alternative assays and compared the findings to their known inmore » vivo developmental toxicity. Triazoles are antifungal agents used in agriculture and medicine, some of which are known to induce craniofacial and limb abnormalities in rodents. The WEC showed a general pattern of teratogenic effects, typical of exposure to triazoles, mainly consisting of reduction and fusion of the first and second branchial arches, which are in accordance with the craniofacial malformations reported after in vivo exposure. In the EST all triazole compounds inhibited cardiomyocyte differentiation concentration-dependently. Overall, the ZET gave the best correlation with the relative in vivo developmental toxicities of the tested compounds, closely followed by the EST. The relative potencies observed in the WEC showed the lowest correlation with the in vivo developmental toxicity data. These differences in the efficacy between the test systems might be due to differences in compound kinetics, in developmental stages represented and in the relative complexity of the alternative assays.« less

Comparison of the mouse Embryonic Stem cell Test, the rat Whole Embryo Culture and the Zebrafish Embryotoxicity Test as alternative methods for developmental toxicity testing of six 1,2,4-triazoles.

PubMed

de Jong, Esther; Barenys, Marta; Hermsen, Sanne A B; Verhoef, Aart; Ossendorp, Bernadette C; Bessems, Jos G M; Piersma, Aldert H

2011-06-01

The relatively high experimental animal use in developmental toxicity testing has stimulated the search for alternatives that are less animal intensive. Three widely studied alternative assays are the mouse Embryonic Stem cell Test (EST), the Zebrafish Embryotoxicity Test (ZET) and the rat postimplantation Whole Embryo Culture (WEC). The goal of this study was to determine their efficacy in assessing the relative developmental toxicity of six 1,2,4-triazole compounds,(1) flusilazole, hexaconazole, cyproconazole, triadimefon, myclobutanil and triticonazole. For this purpose, we analyzed effects and relative potencies of the compounds in and among the alternative assays and compared the findings to their known in vivo developmental toxicity. Triazoles are antifungal agents used in agriculture and medicine, some of which are known to induce craniofacial and limb abnormalities in rodents. The WEC showed a general pattern of teratogenic effects, typical of exposure to triazoles, mainly consisting of reduction and fusion of the first and second branchial arches, which are in accordance with the craniofacial malformations reported after in vivo exposure. In the EST all triazole compounds inhibited cardiomyocyte differentiation concentration-dependently. Overall, the ZET gave the best correlation with the relative in vivo developmental toxicities of the tested compounds, closely followed by the EST. The relative potencies observed in the WEC showed the lowest correlation with the in vivo developmental toxicity data. These differences in the efficacy between the test systems might be due to differences in compound kinetics, in developmental stages represented and in the relative complexity of the alternative assays. Copyright © 2011 Elsevier Inc. All rights reserved.

The oral and craniofacial relevance of chemically modified RNA therapeutics.

PubMed

Elangovan, Satheesh; Kormann, Michael S D; Khorsand, Behnoush; Salem, Aliasger K

2016-01-01

Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy, and their combinations are currently being explored for oral and craniofacial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions.

The Oral and Craniofacial Relevance of Chemically Modified RNA Therapeutics

PubMed Central

Kormann, Michael S.D.; Khorsand, Behnoush

2016-01-01

Several tissue engineering strategies in the form of protein therapy, gene therapy, cell therapy and its combinations are currently being explored for oral and cranio-facial regeneration and repair. Though each of these approaches has advantages, they all have common inherent drawbacks of being expensive and raising safety concerns. Using RNA (encoding therapeutic protein) has several advantages that have the potential to overcome these limitations. Chemically modifying the RNA improves its stability and mitigates immunogenicity allowing for the potential of RNA to become an alternative to protein and gene based therapies. This brief review article focuses on the potential of RNA therapeutics in the treatment of disorders in the oral and craniofacial regions. PMID:26896600

Family Members as Participants on Craniofacial Teams.

ERIC Educational Resources Information Center

Andrews, James; Seaver, Earl; Stevens, George; Whiteley, Joseph

1998-01-01

Family members (N=83) who participated in professional team staffing concerning treatment plans for their child with a craniofacial difference (typically, cleft lip and/or palate) were surveyed. Ninety-seven percent of respondents said they would choose to meet with the team on their next visit to the clinic. The role of early interventionists on…

76 FR 23612 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: May 23, 2011. Open: 8:30 a.m...

78 FR 50426 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

76 FR 51995 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: September 19, 2011. Open: 8:30...

77 FR 49820 - National Institute of Dental & Craniofacial Research; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: September 21, 2012. Open: 8:30...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory Dental and... Committee: National Advisory Dental and Craniofacial Research Council. Date: May 21, 2013. Open: 8:30 a.m...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be...

78 FR 45934 - The National Institute of Dental and Craniofacial Research (NIDCR) Strategic Plan Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-30

... a new strategic plan to guide the Institute's research efforts and priorities over the next six... areas identified below. (1) ``Transformative'' areas of research where new discoveries could have the greatest benefit for advancing dental, oral, and craniofacial research. (2) New technical capabilities or...

3D-Printing Technologies for Craniofacial Rehabilitation, Reconstruction, and Regeneration.

PubMed

Nyberg, Ethan L; Farris, Ashley L; Hung, Ben P; Dias, Miguel; Garcia, Juan R; Dorafshar, Amir H; Grayson, Warren L

2017-01-01

The treatment of craniofacial defects can present many challenges due to the variety of tissue-specific requirements and the complexity of anatomical structures in that region. 3D-printing technologies provide clinicians, engineers and scientists with the ability to create patient-specific solutions for craniofacial defects. Currently, there are three key strategies that utilize these technologies to restore both appearance and function to patients: rehabilitation, reconstruction and regeneration. In rehabilitation, 3D-printing can be used to create prostheses to replace or cover damaged tissues. Reconstruction, through plastic surgery, can also leverage 3D-printing technologies to create custom cutting guides, fixation devices, practice models and implanted medical devices to improve patient outcomes. Regeneration of tissue attempts to replace defects with biological materials. 3D-printing can be used to create either scaffolds or living, cellular constructs to signal tissue-forming cells to regenerate defect regions. By integrating these three approaches, 3D-printing technologies afford the opportunity to develop personalized treatment plans and design-driven manufacturing solutions to improve aesthetic and functional outcomes for patients with craniofacial defects.

3D-Printing Technologies for Craniofacial Rehabilitation, Reconstruction, and Regeneration

PubMed Central

Nyberg, Ethan L.; Farris, Ashley L.; Hung, Ben P.; Dias, Miguel; Garcia, Juan R.; Dorafshar, Amir H.; Grayson, Warren L.

2016-01-01

The treatment of craniofacial defects can present many challenges due to the variety of tissue-specific requirements and the complexity of anatomical structures in that region. 3D-printing technologies provide clinicians, engineers and scientists with the ability to create patient-specific solutions for craniofacial defects. Currently, there are 3 key strategies that utilize these technologies to restore both appearance and function to patients: rehabilitation, reconstruction and regeneration. In rehabilitation, 3D-printing can be used to create prostheses to replace or cover damaged tissues. Reconstruction, through plastic surgery, can also leverage 3D-printing technologies to create custom cutting guides, fixation devices, practice models and implanted medical devices to improve patient outcomes. Regeneration of tissue attempts to replace defects with biological materials. 3D-printing can be used to create either scaffolds or living, cellular constructs to signal tissue-forming cells to regenerate defect regions. By integrating these three approaches, 3D-printing technologies afford the opportunity to develop personalized treatment plans and design-driven manufacturing solutions to improve aesthetic and functional outcomes for patients with craniofacial defects. PMID:27295184

Molecular basis of Williams-Beuren syndrome: TFII-I regulated targets involved in craniofacial development.

PubMed

Makeyev, Aleksandr V; Bayarsaihan, Dashzeveg

2011-01-01

The aim of this study is to identify gene targets of TFII-I transcription factors involved in craniofacial development. Recent findings in individuals with Williams-Beuren syndrome who show facial dysmorphism and cognitive defects have pointed to TFII-I genes (GTF2I and GTF2IRD1) as the prime candidates responsible for these clinical features. However, TFII-I proteins are multifunctional transcriptional factors regulating a number of genes during development, and how their haploinsufficiency leads to the Williams-Beuren syndrome phenotype is currently unknown. Here we report the identification of three genes with a well-established relevance to craniofacial development as direct TFII-I targets. These genes, craniofacial development protein 1 (Cfdp1), Sec23 homolog A (Sec23a), and nuclear receptor binding SET domain protein 1 (Nsd1), contain consensus TFII-I binding sites in their proximal promoters; the chromatin immunoprecipitation analysis showed that TFII-I transcription factors are recruited to these sites in vivo. The results suggest that transcriptional regulation of these genes by TFII-I proteins could provide a possible genotype-phenotype link in Williams-Beuren syndrome.

Elastic Properties of Chimpanzee Craniofacial Cortical Bone

PubMed Central

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

2017-01-01

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. PMID:27870344

Craniofacial divergence and ongoing adaptation via the hedgehog pathway.

PubMed

Roberts, Reade B; Hu, Yinan; Albertson, R Craig; Kocher, Thomas D

2011-08-09

Adaptive variation in craniofacial structure contributes to resource specialization and speciation, but the genetic loci that underlie craniofacial adaptation remain unknown. Here we show that alleles of the hedgehog pathway receptor Patched1 (Ptch1) gene are responsible for adaptive variation in the shape of the lower jaw both within and among genera of Lake Malawi cichlid fish. The evolutionarily derived allele of Ptch1 reduces the length of the retroarticular (RA) process of the lower jaw, a change predicted to increase speed of jaw rotation for improved suction-feeding. The alternate allele is associated with a longer RA and a more robustly mineralized jaw, typical of species that use a biting mode of feeding. Genera with the most divergent feeding morphologies are nearly fixed for different Ptch1 alleles, whereas species with intermediate morphologies still segregate variation at Ptch1. Thus, the same alleles that help to define macroevolutionary divergence among genera also contribute to microevolutionary fine-tuning of adaptive traits within some species. Variability of craniofacial morphology mediated by Ptch1 polymorphism has likely contributed to niche partitioning and ecological speciation of these fishes.

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.

Postnatal treatment factors affecting craniofacial morphology of unilateral cleft lip and palate (UCLP) patients in a Japanese population.

PubMed

Alam, M K; Iida, J; Sato, Y; Kajii, Takashi S

2013-12-01

We have evaluated the craniofacial morphology of Japanese patients with unilateral cleft lip and palate (UCLP) and assessed the various postnatal factors that affect it. Lateral cephalograms of 140 subjects (mean (SD) aged 7 (2) years) with UCLP were taken before orthodontic treatment. Surgeons from Hokkaido University Hospital had done the primary operations. The craniofacial morphology was assessed by angular and linear cephalometric measurements. Cheiloplasty, palatoplasty, and preoperative orthopaedic treatment were chosen as postnatal factors. To compare the assessments of the postnatal factors, we made angular and linear cephalometric measurements for each subject and converted them into Z scores in relation to the mean (SD) of the two variables. Subjects treated by the modified Millard cheiloplasty had larger sella-nasion-point A (SNA) and nasion-point A-pogonion (NA-POG) measurements than subjects treated by the modified Millard with a vomer flap cheiloplasty. Two-stage palatoplasty showed consistently better craniofacial morphology than the other palatoplasty. Subjects who had preoperative orthopaedic treatment with a Hotz plate had significantly larger upper incisor/sella-nasion (U1-SN) measurements than who had no preoperative orthopaedic treatment or an active plate. We conclude that in subjects treated by a modified Millard type of cheiloplasty, a two-stage palatoplasty, and a Hotz plate there were fewer adverse effects on craniofacial morphology. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Customized "In-Office" Three-Dimensional Printing for Virtual Surgical Planning in Craniofacial Surgery.

PubMed

Mendez, Bernardino M; Chiodo, Michael V; Patel, Parit A

2015-07-01

Virtual surgical planning using three-dimensional (3D) printing technology has improved surgical efficiency and precision. A limitation to this technology is that production of 3D surgical models requires a third-party source, leading to increased costs (up to $4000) and prolonged assembly times (averaging 2-3 weeks). The purpose of this study is to evaluate the feasibility, cost, and production time of customized skull models created by an "in-office" 3D printer for craniofacial reconstruction. Two patients underwent craniofacial reconstruction with the assistance of "in-office" 3D printing technology. Three-dimensional skull models were created from a bioplastic filament with a 3D printer using computed tomography (CT) image data. The cost and production time for each model were measured. For both patients, a customized 3D surgical model was used preoperatively to plan split calvarial bone grafting and intraoperatively to more efficiently and precisely perform the craniofacial reconstruction. The average cost for surgical model production with the "in-office" 3D printer was $25 (cost of bioplastic materials used to create surgical model) and the average production time was 14  hours. Virtual surgical planning using "in office" 3D printing is feasible and allows for a more cost-effective and less time consuming method for creating surgical models and guides. By bringing 3D printing to the office setting, we hope to improve intraoperative efficiency, surgical precision, and overall cost for various types of craniofacial and reconstructive surgery.

Distraction osteogenesis in the surgical management of syndromic craniosynostosis: a comprehensive review of published papers.

PubMed

Al-Namnam, N M N; Hariri, F; Rahman, Z A A

2018-04-13

Our aim was to summarise current published evidence about the prognosis of various techniques of craniofacial distraction osteogenesis, particularly its indications, protocols, and complications. Published papers were acquired from online sources using the keywords "distraction osteogenesis", "Le Fort III", "monobloc", and "syndromic craniosynostosis" in combination with other keywords, such as "craniofacial deformity" and "midface". The search was confined to publications in English, and we followed the guidelines of the PRISMA statement. We found that deformity of the skull resulted mainly from Crouzon syndrome. Recently craniofacial distraction has been achieved by monobloc distraction osteogenesis using an external distraction device during childhood, while Le Fort III distraction osteogenesis was used in maturity. Craniofacial distraction was indicated primarily to correct increased intracranial pressure, exorbitism, and obstructive sleep apnoea in childhood, while midface hypoplasia was the main indication in maturity. Overall the most commonly reported complications were minor inflammatory reactions around the pins, and anticlockwise rotation when using external distraction systems. The mean amount of bony advancement was 12.3mm for an external device, 18.6mm for an internal device and 18.7mm when both external and internal devices were used. Treatment by craniofacial distraction must be validated by long-term studies as there adequate data are lacking, particularly about structural relapse and the assessment of function. Copyright © 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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.

Using the Patient Reported Outcomes Measurement Information System to Evaluate Psychosocial Functioning among Children with Craniofacial Anomalies.

PubMed

Shapiro, Danielle N; Waljee, Jennifer; Ranganathan, Kavitha; Buchman, Steven; Warschausky, Seth

2015-06-01

Children with craniofacial anomalies are at risk for social exclusion, bullying, and psychological symptoms, all of which are associated with poor developmental and health outcomes. The National Institutes of Health-developed Patient Reported Outcomes Measurement Information System instruments may be useful tools for monitoring psychosocial functioning in clinical settings and for integrating patient and parent perspectives. The current study included 74 children (50 percent male) with craniofacial anomalies recruited through a multidisciplinary clinic. The authors obtained child self-report and parent-proxy ratings of depression, anxiety, and peer relationship quality using National Institutes of Health Patient Reported Outcomes Measurement Information System instruments. The authors compared sample means to Patient Reported Outcomes Measurement Information System instruments norms and analyzed the reliability of parents' and children's reporting of psychosocial variables. All reliability statistics were satisfactory (α values ranging from 0.74 to 0.96) and sample standard deviations were similar to those obtained in a general population, suggesting that Patient Reported Outcomes Measurement Information System instruments are reliable among children with craniofacial anomalies. In general, children and parents did not report unusual levels of psychological distress; however, they did report poorer peer relationship quality relative to normed data, a trend that was particularly pronounced among boys. National Institutes of Health Patient Reported Outcomes Measurement Information System instruments are efficient and accurate tools for monitoring psychosocial adjustment among children with craniofacial anomalies. It may be especially important to monitor social functioning, particularly among boys.

Psychological impact of visible differences in patients with congenital craniofacial anomalies.

PubMed

Singh, Varun Pratap; Moss, Timothy P

2015-01-01

Patients with craniofacial anomalies often have appearance concerns and related social anxiety which can affect their quality of life. This study assessed the psychological impact of facial and dental appearance in patients with craniofacial anomalies in comparison to a general population control group. The study involved 102 adult patients (51% male) with congenital craniofacial anomalies and 102 controls (49% male). Both groups completed the Nepali version of Derriford Appearance Scale (DAS) and the Psychological Impact of Dental Aesthetic Questionnaire (PIDAQ) in a clinical setting to assess appearance-related distress, avoidance, and anxiety. There was a significant difference between patients and controls on both PIDAQ (mean score for patients 33.25 ± 9.45 while for controls 27.52 ± 5.67, p < 0.001) and DAS59 scores (mean score for patients 159.16 ± 31.54 while for controls 77.64 ± 6.57, p < 0.001), indicating that patients experienced greater negative psychological impact of living with their appearance (PIDAQ) and more appearance-related distress (DAS) than controls. DAS scores were not associated with gender. There was no association of the place of residence (rural vs. urban) with PIDAQ or DAS59 scores. There is a significant psychological impact of altered facial and dental appearance in patients with craniofacial anomalies compared to controls. There was no effect of locality (rural/urban) on the psychological impact of facial and dental appearance in patients.

Three-dimensional Procrustes analysis of modern human craniofacial form.

PubMed

Badawi-Fayad, Jackie; Cabanis, Emmanuel-Alain

2007-03-01

The objective of this study was to analyze modern human craniofacial form using 3D Procrustes superimposition in order to establish a reference model and validate it on computed tomography (CT). The sample consists of 136 specimens from five modern human regional groups. Thirty-three craniofacial landmark coordinates have been recorded using a Microscribe and calculated on CT scans for five crania from the sample. Procrustes superimposition has been performed to calculate the mean shape, and a discriminant analysis has also been carried out to estimate the variability of shape. The results show that the repeatability of measurements made on CT and on Microscribe is excellent (R = 0.99). There is no major distinctiveness in the craniofacial shape; however, discriminant function 1 separates out the European crania from the others, especially African and American. It includes the width and the length of the face, the flatness of the upper face, the prognathism of the maxilla, as well as the length and the inclination of the palate. The width of the maxilla and the palate do not show a great variability. This may be the common invariant feature responsible for the alignment of the teeth in all specimens. It may correspond to functional patterns related to masticatory constraints manifested by the important interproximal and occlusal dental wear in all specimens. This study confirms the high accuracy of measurements made on CT scan and the importance of geometric morphometrics, which provides an accurate characterization of the overall craniofacial shape and its variation within the entire population.

A regional method for craniofacial reconstruction based on coordinate adjustments and a new fusion strategy.

PubMed

Deng, Qingqiong; Zhou, Mingquan; Wu, Zhongke; Shui, Wuyang; Ji, Yuan; Wang, Xingce; Liu, Ching Yiu Jessica; Huang, Youliang; Jiang, Haiyan

2016-02-01

Craniofacial reconstruction recreates a facial outlook from the cranium based on the relationship between the face and the skull to assist identification. But craniofacial structures are very complex, and this relationship is not the same in different craniofacial regions. Several regional methods have recently been proposed, these methods segmented the face and skull into regions, and the relationship of each region is then learned independently, after that, facial regions for a given skull are estimated and finally glued together to generate a face. Most of these regional methods use vertex coordinates to represent the regions, and they define a uniform coordinate system for all of the regions. Consequently, the inconsistence in the positions of regions between different individuals is not eliminated before learning the relationships between the face and skull regions, and this reduces the accuracy of the craniofacial reconstruction. In order to solve this problem, an improved regional method is proposed in this paper involving two types of coordinate adjustments. One is the global coordinate adjustment performed on the skulls and faces with the purpose to eliminate the inconsistence of position and pose of the heads; the other is the local coordinate adjustment performed on the skull and face regions with the purpose to eliminate the inconsistence of position of these regions. After these two coordinate adjustments, partial least squares regression (PLSR) is used to estimate the relationship between the face region and the skull region. In order to obtain a more accurate reconstruction, a new fusion strategy is also proposed in the paper to maintain the reconstructed feature regions when gluing the facial regions together. This is based on the observation that the feature regions usually have less reconstruction errors compared to rest of the face. The results demonstrate that the coordinate adjustments and the new fusion strategy can significantly improve the craniofacial reconstructions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the NIDCR Special Grants Review Committee, October 17, 2013, 8:00 a.m. to October 18, 2013, 12:00 p.m., NIH Building...

One-stage closure of isolated cleft palate with the Veau-Wardill-Kilner V to Y pushback procedure or the Cronin modification. III. Comparison of lateral craniofacial morphology.

PubMed

Heliövaara, A; Ranta, R

1993-10-01

The craniofacial morphology of 116 consecutive patients with isolated cleft palate was studied by means of lateral cephalograms at 17 to 20 years of age. One-stage hard- and soft-palate closure had been carried out at the mean age of 1.8 years by using the Veau-Wardill-Kilner or the Cronin mucoperiosteal palatal V-Y pushback technique. In the Veau-Wardill-Kilner group the cranial base was longer, the cranial base angle was larger, and the mandible longer and its ramus higher but less backward rotated. The patients with originally the most extensive clefts showed the most marked deviations in craniofacial morphology at adult age.

Diprosopus (partially duplicated head) associated with anencephaly: a case report.

PubMed

al Muti Zaitoun, A; Chang, J; Booker, M

1999-01-01

Craniofacial duplication (diprosopus) is a rare form of conjoined twin. A 16 year old mother with a twin pregnancy delivered one normally formed baby boy and one diprosopus male. The malformed baby was 33 weeks of gestation with a single trunk, normal limbs and various degrees of facial duplication. Of the following structures there were two of each: noses, eyes, ears (and one dimple), mouths, tongues and, with bilateral central cleft lips and cleft palates. This was associated with holoprosencephaly and craniorachischisis. Internal organs showed no duplication. There were multiple congenital anomalies including diaphragmatic hernia, small lungs, two lobes of the right lung, ventricular septal defect, small adrenal gland and small left kidney with short ureter. The body also had a short neck, small chest cavities and kyphosis. X-ray revealed duplication of the vertebral column. The case presented here represents a type II of diprosopia of Rating (1933) and is the least common type reported. We also reviewed 22 recently reported cases of diprosopus. In addition to facial duplication, anencephaly, neural tube defect and cardiac malformations represent the more common congenital abnormalities associated with diprosopus. The pathogenesis of diprosopus is not well understood. Factors that play a role in diprosopus are probably similar to those factors (genetic, environmental and abnormal placental circulation) which affect monozoygotic twins as observed in this case report. Early ultrasonography diagnosis of diprosopus permits one to consider a vaginal therapeutic abortion.

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

PubMed Central

Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

2016-01-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams–Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation. PMID:27617154

The first Korean patient with Potocki-Shaffer syndrome: a rare cause of multiple exostoses.

PubMed

Sohn, Young Bae; Yim, Shin-Young; Cho, Eun-Hae; Kim, Ok-Hwa

2015-02-01

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)×1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature.

PubMed

Abbas, Elham; Cox, Devin M; Smith, Teri; Butler, Merlin G

2016-09-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation.

The Protein Tyrosine Phosphatase Shp2 Is Required for the Generation of Oligodendrocyte Progenitor Cells and Myelination in the Mouse Telencephalon

PubMed Central

Ehrman, Lisa A.; Nardini, Diana; Ehrman, Sarah; Rizvi, Tilat A.; Gulick, James; Krenz, Maike; Dasgupta, Biplab; Robbins, Jeffrey; Ratner, Nancy; Nakafuku, Masato

2014-01-01

The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities. To gain insight into requirements for Shp2 (LOF) and the impact of abnormal Shp2 GOF mutations, we used a Shp2 conditional mutant allele (LOF) and a cre inducible Shp2-Q79R GOF transgenic mouse in combination with Olig2cre/+ mice to target embryonic ventral telencephalic progenitors and the oligodendrocyte lineage. In the absence of Shp2 (LOF), neuronal cell types originating from progenitors in the ventral telencephalon were generated, but oligodendrocyte progenitor cell (OPC) generation was severely impaired. Late embryonic and postnatal Shp2 cKOs showed defects in the generation of OPCs throughout the telencephalon and subsequent reductions in white matter myelination. Conversely, transgenic expression of the Shp2 GOF Noonan syndrome mutation resulted in elevated OPC numbers in the embryo and postnatal brain. Interestingly, expression of this mutation negatively influenced myelination as mice displayed abnormal myelination and fewer myelinated axons in the white matter despite elevated OPC numbers. Increased proliferating OPCs and elevated MAPK activity were also observed during oligodendrogenesis after expression of Shp2 GOF mutation. These results support the notion that appropriate Shp2 activity levels control the number as well as the differentiation of oligodendrocytes during development. PMID:24599474

The protein tyrosine phosphatase Shp2 is required for the generation of oligodendrocyte progenitor cells and myelination in the mouse telencephalon.

PubMed

Ehrman, Lisa A; Nardini, Diana; Ehrman, Sarah; Rizvi, Tilat A; Gulick, James; Krenz, Maike; Dasgupta, Biplab; Robbins, Jeffrey; Ratner, Nancy; Nakafuku, Masato; Waclaw, Ronald R

2014-03-05

The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities. To gain insight into requirements for Shp2 (LOF) and the impact of abnormal Shp2 GOF mutations, we used a Shp2 conditional mutant allele (LOF) and a cre inducible Shp2-Q79R GOF transgenic mouse in combination with Olig2(cre/+) mice to target embryonic ventral telencephalic progenitors and the oligodendrocyte lineage. In the absence of Shp2 (LOF), neuronal cell types originating from progenitors in the ventral telencephalon were generated, but oligodendrocyte progenitor cell (OPC) generation was severely impaired. Late embryonic and postnatal Shp2 cKOs showed defects in the generation of OPCs throughout the telencephalon and subsequent reductions in white matter myelination. Conversely, transgenic expression of the Shp2 GOF Noonan syndrome mutation resulted in elevated OPC numbers in the embryo and postnatal brain. Interestingly, expression of this mutation negatively influenced myelination as mice displayed abnormal myelination and fewer myelinated axons in the white matter despite elevated OPC numbers. Increased proliferating OPCs and elevated MAPK activity were also observed during oligodendrogenesis after expression of Shp2 GOF mutation. These results support the notion that appropriate Shp2 activity levels control the number as well as the differentiation of oligodendrocytes during development.

Craniofacial morphology in ancient and modern Greeks through 4,000 years.

PubMed

Papagrigorakis, Manolis J; Kousoulis, Antonis A; Synodinos, Philippos N

2014-01-01

Multiple 20th century studies have speculated on the anthropological similarities of the modern inhabitants of Greece with their ancient predecessors. The present investigation attempts to add to this knowledge by comparing the craniofacial configuration of 141 ancient (dating around 2,000-500 BC) and 240 modern Greek skulls (the largest material among relevant national studies). Skulls were grouped in age at death, sex, era and geographical categories; lateral cephalograms were taken and 53 variables were measured and correlated statistically. The craniofacial measurements and measurements of the basic quadrilateral and cranial polygon were compared in various groups using basic statistical methods, one-way ANOVA and assessment of the correlation matrices. Most of the measurements for both sexes combined followed an akin pattern in ancient and modern Greek skulls. Moreover, sketching and comparing the outline of the skull and upper face, we observed a clock-wise movement. The present study confirms that the morphological pattern of Greek skulls, as it changed during thousands of years, kept some characteristics unchanged, with others undergoing logical modifications. The analysis of our results allows us to believe that the influence upon the craniofacial complex of the various known factors, including genetic or environmental alterations, is apt to alter its form to adapt to new conditions. Even though 4,000 years seems too narrow a span to provoke evolutionary insights using conventional geometric morphometrics, the full presentation of our results makes up a useful atlas of solid data. Interpreted with caution, the craniofacial morphology in modern and ancient Greeks indicates elements of ethnic group continuation within the unavoidable multicultural mixtures.

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

PubMed

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

2013-09-01

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

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

PubMed

Wang, Qian; Dechow, Paul C

2006-11-01

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

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

PubMed Central

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

2011-01-01

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

75 FR 1063 - National Institute of Dental & Craniofacial Research; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental & Craniofacial Research; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of the following meeting. The meeting will be closed to the public in accordance...

BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction.

PubMed

Friedman, C D; Costantino, P D; Takagi, S; Chow, L C

1998-01-01

BoneSource-hydroxyapatite cement is a new self-setting calcium phosphate cement biomaterial. Its unique and innovative physical chemistry coupled with enhanced biocompatibility make it useful for craniofacial skeletal reconstruction. The general properties and clinical use guidelines are reviewed. The biomaterial and surgical applications offer insight into improved outcomes and potential new uses for hydroxyapatite cement systems.

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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Nonsynonymous Mutation in the Transcriptional Regulator lbh Is Associated with Cichlid Craniofacial Adaptation and Neural Crest Cell Development

PubMed Central

Powder, Kara E.; Cousin, Hélène; McLinden, Gretchen P.; Craig Albertson, R.

2014-01-01

Since the time of Darwin, biologists have sought to understand the origins and maintenance of life’s diversity of form. However, the nature of the exact DNA mutations and molecular mechanisms that result in morphological differences between species remains unclear. Here, we characterize a nonsynonymous mutation in a transcriptional coactivator, limb bud and heart homolog (lbh), which is associated with adaptive variation in the lower jaw of cichlid fishes. Using both zebrafish and Xenopus, we demonstrate that lbh mediates migration of cranial neural crest cells, the cellular source of the craniofacial skeleton. A single amino acid change that is alternatively fixed in cichlids with differing facial morphologies results in discrete shifts in migration patterns of this multipotent cell type that are consistent with both embryological and adult craniofacial phenotypes. Among animals, this polymorphism in lbh represents a rare example of a coding change that is associated with continuous morphological variation. This work offers novel insights into the development and evolution of the craniofacial skeleton, underscores the evolutionary potential of neural crest cells, and extends our understanding of the genetic nature of mutations that underlie divergence in complex phenotypes. PMID:25234704

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.

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 E 3  > E 2  > E 1 . 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.

The Partnership of Medical Genetics and Oral and Maxillofacial Surgery When Evaluating Craniofacial Anomalies.

PubMed

Lin, Angela E

2015-12-01

A medical geneticist who has an interest in craniofacial anomalies forms a natural partnership with an oral and maxillofacial surgeon, which facilitates patient care. Using complementary diagnostic and therapeutic skills, the search for a recognizable pattern can lead to a syndrome diagnosis. After the initial examination, there is usually genetic testing to confirm the clinical diagnosis. Once established, care coordination and genetic counseling can be provided for the parents and the patient. Enrolling the patient into a research study could be helpful to understand the diagnosis but, in some circumstances, might not have immediate clinical relevance. A multidisciplinary craniofacial team is generally necessary for long-term management. This article discusses illustrative patients evaluated from 2007 through 2011 with the senior oral and maxillofacial surgeon at the Massachusetts General Hospital (Leonard B. Kaban, DMD, MD). These include single patients with the Nablus mask-like facies syndrome and auriculo-condylar syndrome and a series of 20 patients with Gorlin syndrome followed by a multispecialty team. A successful collaboration between a medical geneticist and an oral and maxillofacial surgeon optimizes the treatment of patients with craniofacial anomalies. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Efficient free-form surface representation with application in orthodontics

NASA Astrophysics Data System (ADS)

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

1999-03-01

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

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

PubMed Central

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

2010-01-01

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

Linkage mapping of the primary disease locus for collie eye anomaly.

PubMed

Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A

2003-07-01

Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.

Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: A new X-linked multiple congenital anomalies/mental retardation syndrome: Clinical description and molecular studies

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

Hamel, B.C.J.; Mariman, E.C.M.; Beersum, S.E.C. van

1994-07-15

We report on two brothers and their two maternal uncles with severe mental retardation, congenital heart defect, cleft or highly arched palate, short stature and craniofacial anomalies consisting of microcephaly, abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, and micro-gnathia. Three of the four patients died at an early age. The mother of the two brothers had an atrial septal defect. She is assumed to be manifesting carrier of a mutant gene, which is expressed in her two sons and two brothers. By multipoint linkage analysis it is found that the most likely location of the responsible gene ismore » the pericentromeric region Xp21.3-q21.3 with DMD and DXS3 as flanking markers. Maximum information is obtained with marker DXS453 (Z = 1.20 at {theta} = 0.0). 24 refs., 12 figs., 1 tab.« less

Anesthesia for cesarean delivery in an achondroplastic dwarf: a case report.

PubMed

Huang, Jeffrey; Babins, Noah

2008-12-01

There are more than 100 different types of dwarfism. Achondroplasia is the most common form of this rare condition. The incidence of achondroplasia in the United States is about 15 per 1 million births. Although inherited as an autosomal dominant condition, 80% of cases result from spontaneous mutation. Underdevelopment and premature ossification of bones result in characteristic craniofacial and spinal abnormalities. Limited neck extension, foramen magnum stenosis, a large tongue, large mandible, and atlanto-axial instability can lead to increased difficulty of airway management. Severe kyphosis, scoliosis, spinal stenosis, and unpredictable spread of local anesthetics in the epidural space and subarachnoid space lead to reluctance to apply regional anesthesia in this patient group. In addition, pregnancy in a person with achondroplasis poses more problems for anesthetic selection. These problems include potential hypoxia, severely decreased functional residual capacity, risk of gastric aspiration, and supine hypotension. In this case report, we describe the anesthetic management of an achondroplastic dwarf who underwent cesarean delivery.

Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.

PubMed

Morrison, David G; Elsas, Frederick J; Descartes, Maria

2005-04-01

Isotretinoin (RA), used for the treatment of cystic acne, is a powerful teratogen, causing craniofacial dysmorphisms and neural tube defects. We present two patients with RA embryopathy and oculomotor nerve synkinesis. Retrospective review of patient records. Two patients presented with third nerve synkinesis and fetal RA exposure. Both had marked elevation of the upper eyelids on adduction such that the lid fissures alternately opened and closed on gaze from side to side. Both patients showed typical dysmorphisms of RA embryopathy. The first patient had complete agenesis of the cerebellar vermix and died at 2 years. The second patient had restricted extraocular muscles in one eye and was exotropic and hypotropic. Both patients demonstrated simultaneous innervation of the medial rectus and levator palpebrae muscles causing coincident lid elevation in adduction. This evidence of oculomotor nerve synkinesis is consistent with animal studies showing abnormalities in the formation of cranial nerve ganglia following fetal RA exposure. RA is a powerful teratogen. These patients provide additional clinical evidence of its influence on neural migration during early development.

Oral manifestations and dental management of a child with Zellweger syndrome.

PubMed

Lertsirivorakul, Jinda; Wongswadiwat, Malinee; Treesuwan, Panta

2014-01-01

Zellweger syndrome (ZS) is a rare autosomal recessive disorder, resulting from an impairment in peroxisome function. It is characterized by craniofacial dysmorphism and neurological abnormalities, and involves several systems, which may complicate dental and anesthesia management. The case of a 7-year-old girl diagnosed with ZS is described with emphasis on oral manifestations, oral rehabilitation under general anesthesia (GA), and home oral care. Apart from the unique features of ZS, she presented with clinodactyly, distinctive palatal vault, Class III malocclusion, missing teeth, microdontia, and delayed dental formation. Dental treatment under GA was conducted with concerns of risk of respiratory insufficiency. Oral home care by the parent and regular recall visits were essential to maintain good oral health. Children with ZS may survive into late childhood. They, however, present multiple health problems that are of special concern for not only the pediatric dentist but also the anesthesiologist. Collaboration with the medical team is essential for optimal care of these patients. ©2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

ZIC2 in Holoprosencephaly.

PubMed

Barratt, Kristen S; Arkell, Ruth M

2018-01-01

The ZIC2 transcription factor is one of the most commonly mutated genes in Holoprosencephaly (HPE) probands. HPE is a severe congenital defect of forebrain development which occurs when the cerebral hemispheres fail to separate during the early stages of organogenesis and is typically associated with mispatterning of the embryonic midline. Recent study of genotype-phenotype correlations in HPE cases has defined distinctive features of ZIC2-associated HPE presentation and genetics, revealing that ZIC2 mutation does not produce the craniofacial abnormalities generally thought to characterise HPE but leads to a range of non-forebrain phenotypes. Furthermore, the studies confirm the extent of ZIC2 allelic heterogeneity and that pathogenic variants of ZIC2 are associated with both classic and middle interhemispheric variant (MIHV) HPE which arise from defective ventral and dorsal forebrain patterning, respectively. An allelic series of mouse mutants has helped to delineate the cellular and molecular mechanisms by which one gene leads to defects in these related but distinct embryological processes.

Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

PubMed Central

Sørhus, Elin; Incardona, John P; Furmanek, Tomasz; Goetz, Giles W; Scholz, Nathaniel L; Meier, Sonnich; Edvardsen, Rolf B; Jentoft, Sissel

2017-01-01

Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemical-genetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes. DOI: http://dx.doi.org/10.7554/eLife.20707.001 PMID:28117666

Three-dimensional head anthropometric analysis

NASA Astrophysics Data System (ADS)

Enciso, Reyes; Shaw, Alex M.; Neumann, Ulrich; Mah, James

2003-05-01

Currently, two-dimensional photographs are most commonly used to facilitate visualization, assessment and treatment of facial abnormalities in craniofacial care but are subject to errors because of perspective, projection, lack metric and 3-dimensional information. One can find in the literature a variety of methods to generate 3-dimensional facial images such as laser scans, stereo-photogrammetry, infrared imaging and even CT however each of these methods contain inherent limitations and as such no systems are in common clinical use. In this paper we will focus on development of indirect 3-dimensional landmark location and measurement of facial soft-tissue with light-based techniques. In this paper we will statistically evaluate and validate a current three-dimensional image-based face modeling technique using a plaster head model. We will also develop computer graphics tools for indirect anthropometric measurements in a three-dimensional head model (or polygonal mesh) including linear distances currently used in anthropometry. The measurements will be tested against a validated 3-dimensional digitizer (MicroScribe 3DX).

Fibroblast growth factor receptor signaling crosstalk in skeletogenesis.

PubMed

Miraoui, Hichem; Marie, Pierre J

2010-11-02

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

A de novo 1.38 Mb duplication of 1q31.1 in a boy with hemifacial microsomia, anophthalmia, anotia, macrostomia, and cleft lip and palate.

PubMed

Huang, Xue-shuang; Zhu, Bao; Jiang, Hai-ou; Wu, Su-fan; Zhang, Zai-qi; Xiao, Lin; Yi, Li-lan; Zhang, Jian-xiang

2013-04-01

We reported a 2-year-old boy with developmental delay, mild mental retardation, and severe craniofacial malformation, including facial asymmetry with hypoplasia of the left zygoma, maxilla, and mandible, and left anophthalmia and anotia. A genome-wide screen revealed a 1.38 Mb duplication on chromosome 1q31.1, which was absent in his parents and 27 healthy controls. The duplication region contains two Refseq genes, PLA2G4A and C1orf99, which have not been reported to be implicated in craniofacial malformation. Functional studies of these genes and additional clinical analysis are necessary to elucidate the pathogenesis of craniofacial malformation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of craniofacial linear measurements of 20-40 year-old males and females using digital lateral cephalometric radiography in Indonesia

NASA Astrophysics Data System (ADS)

Aurizanti, D.; Suryonegoro, H.; Priaminiarti, M.

2017-08-01

Craniofacial characteristics are one of the sex determination parameters of age after puberty. The aim of this study is to obtain linear measurements using lateral cephalometric radiography of adults aged 20-40 years based on sex in Indonesia. Ten linear craniofacial parameters on 100 digital lateral cephalometric radiographs were measured. Inter-intra observer reliability was tested using Technical Error Measurement. The independent t-test and the Mann-Whitney U test were used to evaluate the significance of the findings. There are significant differences between males and females on 10 of the linear measurements using lateral cephalometric radiography. Lateral cephalometric radiography showed that the linear measurements of 10 cephalometic parameters were higher in males than females, so it can be used to determine sex.

An Account of the Inaugural Tessier Skull Exhibition at the University of Paris Descartes.

PubMed

Dusseldorp, Joseph Richard; Firmin, Françoise

2015-10-01

Paul Tessier is widely regarded as the father of modern craniofacial surgery. Upon his passing in 2008, his private collection of human skulls was purchased by the French Association of Facial Surgeons to ensure the collection would remain in France. The first public exhibition of the skulls was held in the medical museum of the University of Paris Descartes in April 2014. From this collection of skulls and the imagination of Tessier an entirely new specialty was created. Modern craniofacial surgery, now is an integral part of any pediatric plastic surgery department. Cranial and facial osteotomies have also become commonplace in both traumatic and aesthetic surgery. The goals for craniofacial deformity are now a return to completely normal appearance and function, as Tessier always believed they should be.

Craniofacial resection and its role in the management of sinonasal malignancies.

PubMed

Taghi, Ali; Ali, Ahmed; Clarke, Peter

2012-09-01

Sinonasal malignancy is rare, and its presentation is commonly late. There is a wide variety of pathologies with varying natural histories and survival rates. Anatomy of the skull base is extremely complex and tumors are closely related to orbits, frontal lobes and cavernous sinus. Anatomical detail and the late presentation render surgical management a challenging task. A thorough understanding of anatomy and pathology combined with modern neuroimaging and reliable reconstruction within a multidisciplinary team is imperative to carry out skull base surgery effectively. While endoscopic approaches are gaining credibility, clearly, it will be some time before meaningful comparisons with craniofacial resection can be made. Until then, craniofacial resection will remain the gold standard for managing the sinonasal malignancies of the anterior skull base, as it has proved to be safe and effective.

Mesenchymal stem cells and alginate microcarriers for craniofacial bone tissue engineering: A review.

PubMed

Saltz, Adam; Kandalam, Umadevi

2016-05-01

Craniofacial bone is a complex structure with an intricate anatomical and physiological architecture. The defects that exist in this region therefore require a precise control of osteogenesis in their reconstruction. Unlike traditional surgical intervention, tissue engineering techniques mediate bone development with limited postoperative risk and cost. Alginate stands as the premier polymer in bone repair because of its mild ionotropic gelation and excellent biocompatibility, biodegradability, and injectability. Alginate microcarriers are candidates of choice to mediate cells and accommodate into 3-D environment. Several studies reported the use of alginate microcarriers for delivering cells, drugs, and growth factors. This review will explore the potential use of alginate microcarrier for stem cell systems and its application in craniofacial bone tissue engineering. © 2016 Wiley Periodicals, Inc.

Craniofacial skeletal pattern: is it really correlated with the degree of adenoid obstruction?

PubMed Central

Feres, Murilo Fernando Neuppmann; Muniz, Tomas Salomão; de Andrade, Saulo Henrique; Lemos, Maurilo de Mello; Pignatari, Shirley Shizue Nagata

2015-01-01

OBJECTIVE: The aim of this study was to compare the cephalometric pattern of children with and without adenoid obstruction. METHODS: The sample comprised 100 children aged between four and 14 years old, both males and females, subjected to cephalometric examination for sagittal and vertical skeletal analysis. The sample also underwent nasofiberendoscopic examination intended to objectively assess the degree of adenoid obstruction. RESULTS: The individuals presented tendencies towards vertical craniofacial growth, convex profile and mandibular retrusion. However, there were no differences between obstructive and non-obstructive patients concerning all cephalometric variables. Correlations between skeletal parameters and the percentage of adenoid obstruction were either low or not significant. CONCLUSIONS: Results suggest that specific craniofacial patterns, such as Class II and hyperdivergency, might not be associated with adenoid hypertrophy. PMID:26352848

Transcriptional dynamics of a conserved gene expression network associated with craniofacial divergence in Arctic charr.

PubMed

Ahi, Ehsan Pashay; Kapralova, Kalina Hristova; Pálsson, Arnar; Maier, Valerie Helene; Gudbrandsson, Jóhannes; Snorrason, Sigurdur S; Jónsson, Zophonías O; Franzdóttir, Sigrídur Rut

2014-01-01

Understanding the molecular basis of craniofacial variation can provide insights into key developmental mechanisms of adaptive changes and their role in trophic divergence and speciation. Arctic charr (Salvelinus alpinus) is a polymorphic fish species, and, in Lake Thingvallavatn in Iceland, four sympatric morphs have evolved distinct craniofacial structures. We conducted a gene expression study on candidates from a conserved gene coexpression network, focusing on the development of craniofacial elements in embryos of two contrasting Arctic charr morphotypes (benthic and limnetic). Four Arctic charr morphs were studied: one limnetic and two benthic morphs from Lake Thingvallavatn and a limnetic reference aquaculture morph. The presence of morphological differences at developmental stages before the onset of feeding was verified by morphometric analysis. Following up on our previous findings that Mmp2 and Sparc were differentially expressed between morphotypes, we identified a network of genes with conserved coexpression across diverse vertebrate species. A comparative expression study of candidates from this network in developing heads of the four Arctic charr morphs verified the coexpression relationship of these genes and revealed distinct transcriptional dynamics strongly correlated with contrasting craniofacial morphologies (benthic versus limnetic). A literature review and Gene Ontology analysis indicated that a significant proportion of the network genes play a role in extracellular matrix organization and skeletogenesis, and motif enrichment analysis of conserved noncoding regions of network candidates predicted a handful of transcription factors, including Ap1 and Ets2, as potential regulators of the gene network. The expression of Ets2 itself was also found to associate with network gene expression. Genes linked to glucocorticoid signalling were also studied, as both Mmp2 and Sparc are responsive to this pathway. Among those, several transcriptional targets and upstream regulators showed differential expression between the contrasting morphotypes. Interestingly, although selected network genes showed overlapping expression patterns in situ and no morph differences, Timp2 expression patterns differed between morphs. Our comparative study of transcriptional dynamics in divergent craniofacial morphologies of Arctic charr revealed a conserved network of coexpressed genes sharing functional roles in structural morphogenesis. We also implicate transcriptional regulators of the network as targets for future functional studies.

Stress and displacement patterns in the craniofacial skeleton with rapid maxillary expansion: a finite element method study.

PubMed

Gautam, Pawan; Valiathan, Ashima; Adhikari, Raviraj

2007-07-01

The purpose of this finite element study was to evaluate stress distribution along craniofacial sutures and displacement of various craniofacial structures with rapid maxillary expansion (RME) therapy. The analytic model for this study was developed from sequential computed tomography scan images taken at 2.5-mm intervals of a dry young human skull. Subsequently, a finite element method model was developed from computed tomography images by using AutoCAD software (2004 version, Autodesk, Inc, San Rafael, Calif) and ANSYS software (version 10, Belcan Engineering Group, Downers Grove, Ill). The maxilla moved anteriorly and downward and rotated clockwise in response to RME. The pterygoid plates were displaced laterally. The distant structures of the craniofacial skeleton--zygomatic bone, temporal bone, and frontal bone--were also affected by transverse orthopedic forces. The center of rotation of the maxilla in the X direction was somewhere between the lateral and the medial pterygoid plates. In the frontal plane, the center of rotation of the maxilla was approximately at the superior orbital fissure. The maximum von Mises stresses were found along the frontomaxillary, nasomaxillary, and frontonasal sutures. Both tensile and compressive stresses could be demonstrated along the same suture. RME facilitates expansion of the maxilla in both the molar and the canine regions. It also causes downward and forward displacement of the maxilla and thus can contribute to the correction of mild Class III malocclusion. The downward displacement and backward rotation of the maxilla could be a concern in patients with excessive lower anterior facial height. High stresses along the deep structures and the various sutures of the craniofacial skeleton signify the role of the circummaxillary sutural system in downward and forward displacement of the maxilla after RME.

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

PubMed

Sessle, B J

2000-01-01

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

E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells

PubMed Central

Kennedy, Allyson E.; Kandalam, Suraj; Olivares-Navarrete, Rene

2017-01-01

Since electronic cigarette (ECIG) introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM) in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product. PMID:28957438

E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

PubMed

Kennedy, Allyson E; Kandalam, Suraj; Olivares-Navarrete, Rene; Dickinson, Amanda J G

2017-01-01

Since electronic cigarette (ECIG) introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM) in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

Computer-assisted versus conventional free fibula flap technique for craniofacial reconstruction: an outcomes comparison.

PubMed

Seruya, Mitchel; Fisher, Mark; Rodriguez, Eduardo D

2013-11-01

There has been rising interest in computer-aided design/computer-aided manufacturing for preoperative planning and execution of osseous free flap reconstruction. The purpose of this study was to compare outcomes between computer-assisted and conventional fibula free flap techniques for craniofacial reconstruction. A two-center, retrospective review was carried out on patients who underwent fibula free flap surgery for craniofacial reconstruction from 2003 to 2012. Patients were categorized by the type of reconstructive technique: conventional (between 2003 and 2009) or computer-aided design/computer-aided manufacturing (from 2010 to 2012). Demographics, surgical factors, and perioperative and long-term outcomes were compared. A total of 68 patients underwent microsurgical craniofacial reconstruction: 58 conventional and 10 computer-aided design and manufacturing fibula free flaps. By demographics, patients undergoing the computer-aided design/computer-aided manufacturing method were significantly older and had a higher rate of radiotherapy exposure compared with conventional patients. Intraoperatively, the median number of osteotomies was significantly higher (2.0 versus 1.0, p=0.002) and the median ischemia time was significantly shorter (120 minutes versus 170 minutes, p=0.004) for the computer-aided design/computer-aided manufacturing technique compared with conventional techniques; operative times were shorter for patients undergoing the computer-aided design/computer-aided manufacturing technique, although this did not reach statistical significance. Perioperative and long-term outcomes were equivalent for the two groups, notably, hospital length of stay, recipient-site infection, partial and total flap loss, and rate of soft-tissue and bony tissue revisions. Microsurgical craniofacial reconstruction using a computer-assisted fibula flap technique yielded significantly shorter ischemia times amidst a higher number of osteotomies compared with conventional techniques. Therapeutic, III.

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

PubMed

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

2016-02-01

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

Update on 13 Syndromes Affecting Craniofacial and Dental Structures

PubMed Central

Bartzela, Theodosia N.; Carels, Carine; Maltha, Jaap C.

2017-01-01

Care of individuals with syndromes affecting craniofacial and dental structures are mostly treated by an interdisciplinary team from early childhood on. In addition to medical and dental specialists that have a vivid interest in these syndromes and for whom these syndromes are of evident interest, experts of scientific background—like molecular and developmental geneticists, but also computational biologists and bioinformaticians—, become more frequently involved in the refined diagnostic and etiological processes of these patients. Early diagnosis is often crucial for the effective treatment of functional and developmental aspects. However, not all syndromes can be clinically identified early, especially in cases of absence of known family history. Moreover, the treatment of these patients is often complicated because of insufficient medical knowledge, and because of the dental and craniofacial developmental variations. The role of the team is crucial for the prevention, proper function, and craniofacial development which is often combined with orthognathic surgery. Although the existing literature does not provide considerable insight into this topic, this descriptive review aims to provide tools for the interdisciplinary team by giving an update on the genetics and general features, and the oral and craniofacial manifestations for early diagnosis. Clinical phenotyping together with genetic data and pathway information will ultimately pave the way for preventive strategies and therapeutic options in the future. This will improve the prognosis for better functional and aesthetic outcome for these patients and lead to a better quality of life, not only for the patients themselves but also for their families. The aim of this review is to promote interdisciplinary interaction and mutual understanding among all specialists involved in the diagnosis and therapeutic guidance of patients with these syndromal conditions in order to provide optimal personalized care in an integrated approach. PMID:29311971

Facial ontogeny in Neanderthals and modern humans

PubMed Central

Bastir, Markus; O'Higgins, Paul; Rosas, Antonio

2007-01-01

One hundred and fifty years after the discovery of Neanderthals, it is held that this morphologically and genetically distinct human species does not differ from modern Homo sapiens in its craniofacial ontogenetic trajectory after the early post-natal period. This is striking given the evident morphological differences between these species, since it implies that all of the major differences are established by the early post-natal period and carried into adulthood through identical trajectories, despite the extent to which mechanical and spatial factors are thought to influence craniofacial ontogeny. Here, we present statistical and morphological analyses demonstrating that the spatio-temporal processes responsible for craniofacial ontogenetic transformations differ. The findings emphasize that pre-natal as well as post-natal ontogeny are both important in establishing the cranial morphological differences between adult Neanderthals and modern humans. PMID:17311777

[Diagnosis of facial and craniofacial asymmetry].

PubMed

Arnaud, E; Marchac, D; Renier, D

2001-10-01

Craniofacial asymmetry is caused by various aetiologies but clinical examination remains the most important criteria since minor asymmetry is always present. The diagnosis can be confirmed by anthropometric measurements and radiological examinations but only severe asymmetries or asymmetries with an associated functional impairment should be treated. The treatment depends on the cause, and on the time of appearance. Congenital asymmetries might be treated early, during the first year of life if a craniosynostosis is present. Hemifacial microsomia are treated later if there is no breathing impairment. Since the pediatricians have recommended the dorsal position for infant sleeping, an increasing number of posterior flattening of the skull has been appearing, and could be prevented by adequate nursing. Other causes of craniofacial asymmetries are rare and should be adapted to the cause (tumors, atrophies, neurological paralysis, hypertrophies) by a specialized multidisciplinar team.

Severe macroglossia after posterior fossa and craniofacial surgery in children.

PubMed

Bouaoud, J; Joly, A; Picard, A; Thierry, B; Arnaud, E; James, S; Hennessy, I; McGarvey, B; Cairet, P; Vecchione, A; Vergnaud, E; Duracher, C; Khonsari, R H

2018-04-01

Massive swelling of the tongue can occur after posterior fossa and craniofacial surgery. Several hypotheses have been proposed to explain the occurrence of such severe postoperative macroglossia, but this phenomenon is still poorly understood. Severe postoperative macroglossia can be a life-threatening condition due to upper airway obstruction. Three cases of severe postoperative macroglossia that occurred after cervical spine, craniofacial, and posterior fossa surgical procedures are reported here. These cases required specialized maxillofacial management and a prolonged stay in the intensive care unit. Causal factors involved in this condition are reported, in order to highlight appropriate prevention and treatment options adapted to the management of paediatric patients. An overview of the current literature on severe postoperative macroglossia in paediatric populations is also provided. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Differential expression of homeobox-containing genes Msx-1 and Msx-2 and homeoprotein Msx-2 expression during chick craniofacial development.

PubMed

Nishikawa, K; Nakanishi, T; Aoki, C; Hattori, T; Takahashi, K; Taniguchi, S

1994-03-01

The expression pattern of chick Msx-1 and Msx-2 homeobox genes in craniofacial primordia was examined by in situ hybridization using cRNA probes. Both genes were expressed in the distal region of the facial primordia, where the distribution of Msx-2 expression was restricted distally within the Msx-1 expression domain. On the contrary, Msx-2 expression in the lateral choroid plexus and cranial skull was broader and more intensive than Msx-1 expression. Our findings suggest that these two genes cooperate to play differential roles in craniofacial development. Msx-2 protein was detected immunohistochemically, and its localization essentially corresponded to the mRNA expression pattern, substantiating the involvement of Msx-2 protein as a transcriptional regulator in developing limb and face.

Neurocognitive Pattern Analysis of Auditory and Visual Information.

DTIC Science & Technology

1986-02-15

using a stereophotogrammetry system developed for craniofacial research ( Baumrind & Curry, 1984; Curry et al., 1982). 47 EEG S YS TEMS LABORA T ORY (This...thicknesses. IEEE Trans. Biomed, Enqr., BME-28, 447-452. Baumrind , S. & Curry, S. (1984) Merging of data from different re- cords in craniofacial...Research, 35(3), 217-250, Curry, S,, Moffitt,, FH,, Symes, 0. & Baumrind , S. (1982) Family of calibrated stereometric cameras for direct intra-oral use

Developing business opportunities from concept to end point for craniofacial surgeons.

PubMed

Brown, Spencer A

2012-01-01

Craniofacial surgeons repair a wide variety of soft and hard tissues that produce the clinical expertise to recognize the need for an improved device or novel regenerative stem cell or use of molecules that may dramatically change the way clinical care for improved patient outcomes. The business pathway to bring a concept to clinical care requires knowledge, mentoring, and a team of experts in business and patent law.

Application of a Novel Semi-Automatic Technique for Determining the Bilateral Symmetry Plane of the Facial Skeleton of Normal Adult Males.

PubMed

Roumeliotis, Grayson; Willing, Ryan; Neuert, Mark; Ahluwalia, Romy; Jenkyn, Thomas; Yazdani, Arjang

2015-09-01

The accurate assessment of symmetry in the craniofacial skeleton is important for cosmetic and reconstructive craniofacial surgery. Although there have been several published attempts to develop an accurate system for determining the correct plane of symmetry, all are inaccurate and time consuming. Here, the authors applied a novel semi-automatic method for the calculation of craniofacial symmetry, based on principal component analysis and iterative corrective point computation, to a large sample of normal adult male facial computerized tomography scans obtained clinically (n = 32). The authors hypothesized that this method would generate planes of symmetry that would result in less error when one side of the face was compared to the other than a symmetry plane generated using a plane defined by cephalometric landmarks. When a three-dimensional model of one side of the face was reflected across the semi-automatic plane of symmetry there was less error than when reflected across the cephalometric plane. The semi-automatic plane was also more accurate when the locations of bilateral cephalometric landmarks (eg, frontozygomatic sutures) were compared across the face. The authors conclude that this method allows for accurate and fast measurements of craniofacial symmetry. This has important implications for studying the development of the facial skeleton, and clinical application for reconstruction.

Craniofacial variation and dietary adaptations of African colobines.

PubMed

Koyabu, Daisuke B; Endo, Hideki

2009-06-01

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

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

PubMed

Hu, Yinan; Albertson, R Craig

2014-06-10

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

Developmental craniofacial anthropometry: Assessment of Race effects

PubMed Central

Durtschi, Reid B.; Chung, Dongjun; Gentry, Lindell R.; Chung, Moo K.; Vorperian, Houri K.

2010-01-01

Differences in craniofacial anatomy among racial groups have been documented in a variety of structures but the oral and maxillofacial regions have been shown to be a particularly defining region of variability between different racial/ethnic groups. Such comparisons are informative, but they neither address developmental changes of the craniofacial anatomy, nor do they assess or take into account the natural variability within individual races that may account for similar reported, across-group variations. The purpose of this report was to compare – using medical imaging studies – the growth trend of select race sensitive craniofacial variables in the oral and pharyngeal regions when all races: White, Asian, Black, and Hispanic (AR) are included versus only a single race category: White (WR). Race effect was tested by comparing sex specific growth fits (4th degree polynomial model) for AR versus WR data. Findings indicate that the inclusion of all races versus a single race did not significantly alter the growth model fits. Thus, the inclusion of all races permits the advancement of general growth models; however, methodologically it is best to treat the race variable as a covariate in all future analysis to test for both potential all race effects or individual race effects, on general growth models. PMID:19753647

Temporomandibular disorders: referred cranio-cervico-facial clinic.

PubMed

Ramírez, Luis Miguel; Sandoval, German Pablo; Ballesteros, Luis Ernesto

2005-04-01

The bond between temporomandibular disorders and referred craniofacial symptomatology is more and more evident. In it subsists the prevailing necessity of understanding the temporomandibular disorders and the cranio-cervico-facial referred symptomatology from a neurophysiologic and muscle-skeletal perspective contained in the stomatognatic system. Diagnosis in head and neck areas is difficult because of its complex anatomy. Some painful craniofacial syndromes exhibit the same symptoms although they don.t seem objectively possible and that is what confuses the specialist and the patient. Pain in the head and the neck is one of the most complex to diagnose because of its varied origins that can be neurological, vascular, muscular, ligamental and bony. This article seeks to show some reasonable anatomical and pathophysiological connections of this muscle-skeletal disorder expressed with symptoms like tinnitus, otic fullness, otalgia and migraine among others. Disciplines in health such as neurology, the otolaryngology and dentistry share common anatomical and pathophysiological roads constructed in an increased muscular activity that generates muscle-skeletal disorders and is difficult to locate referred craniofacial symptomatology. This revision aspires to sensitize the medical specialist and the odontologist in the understanding of the important interdisciplinary handling in the detection of this disorder. This offers better tools in the conservative therapy phase of this craniofacial referred symptomatology.

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

Hegman, K.; Spikes, A.S.; Orr-Urteger, A.

A genetic evaluation was requested for a 6 week old infant with multiple congenital malformations including mild craniofacial anomalies, truncal hypotonia, hypospadias and a VSD. Blood obtained for chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome analysis showed a 46,XY,inv ins(3;4)(p21.32;q25q21.2),inv(4)(p15.3q21.3) karyotype. Therefore, the proband`s chromosome 4 was the unbalanced product of this insertional translocation from the father resulting in partial monosomy 4q. Additionally, the derivative 4 had a pericentric inversion which was also seen in the father`s chromosome 4. During genetic counseling, the proband`s 2 year-old brother was evaluated. Although he was not felt to be dysmorphic, hemore » was described as having impulsive behavior. Chromosome analysis on this child revealed 46,XY,der(3)inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in partial trisomy 4q. FISH using two-color {open_quotes}painting{close_quotes} probes for chromosomes 3 and 4 confirmed the G-banded interpretation in this family. The segregation seen in this family was due to adjacent I segregation with both reciprocal products observed in the two children. Few patients with partial 4q trisomy or partial 4q monosomy have been described in the literature. This family revealed both possible unbalanced products from adjacent I segregation with partial 4q monosomy showing multiple congenital anomalies and partial 4q trisomy showing very few phenotypic abnormalities.« less

Novel autosomal dominant mandibulofacial dysostosis with ptosis: clinical description and exclusion of TCOF1.

PubMed

Hedera, P; Toriello, H V; Petty, E M

2002-07-01

Treacher Collins syndrome (TCS), the most common type of mandibulofacial dysostosis (MFD), is genetically homogeneous. Other types of MFD are less common and, of these, only the Bauru type of MFD has an autosomal dominant (AD) mode of inheritance established. Here we report clinical features of a kindred with a unique AD MFD with the exclusion of linkage to the TCS locus (TCOF1) on chromosome 5q31-q32. Six affected family members underwent a complete medical genetics physical examination and two affected subjects had skeletal survey. All available medical records were reviewed. Linkage analysis using the markers spanning the TCOF1 locus was performed. One typically affected family member had a high resolution karyotype. Affected subjects had significant craniofacial abnormalities without any significant acral changes and thus had a phenotype consistent with a MFD variant. Distinctive features included hypoplasia of the zygomatic complex, micrognathia with malocclusion, auricular abnormalities with conductive hearing loss, and ptosis. Significantly negative two point lod scores were obtained for markers spanning the TCOF1 locus, excluding the possibility that the disease in our kindred is allelic with TCS. High resolution karyotype was normal. We report a kindred with a novel type of MFD that is not linked to the TCOF1 locus and is also clinically distinct from other types of AD MFD. Identification of additional families will facilitate identification of the gene causing this type of AD MFD and further characterisation of the clinical phenotype.