Desordens hiperostóticas em American Bully / Hiperostotic disorders in american bully

O complexo de desordens hiperostóticas é uma condição rara e autolimitante, que tem as mesmas características histopatológicas, que cursa com proliferação óssea de caráter não neoplásico. Acomete cães jovens de raças distintas, com variabilidade quanto ao tipo de proliferação óssea e quanto aos ossos acometidos. O complexo é composto pela osteopatia craniomandibular, hiperostose da calota craniana e osteodistrofia hipertrófica. Podendo estar presente nos ossos da calota craniana, mandíbulas, coluna cervical e esqueleto apendicular. O presente relato, descreveu o quadro de uma cadela, da raça American Bully, não castrada, três meses de idade, que foi atendida com queixa de aumento de volume doloroso das mandíbulas, hiporexia e sialorreia há 15 dias, apresentando ao exame físico, amplitude de movimento diminuída e sensibilidade dolorosa da articulação temporomandibular, espessamento firme bilateral do crânio em região de fossa temporal, espessamento palpável de consistência firme das mandíbulas e crepitação respiratória. Após avaliação clínica e realização de exames complementares, chegou-se ao diagnóstico presuntivo, de complexo de desordens hiperostóticas. Foi instituído como conduta terapêutica o suporte analgésico, sendo eficaz para a manutenção das necessidades fisiológicas até a paciente alcançar a fase adulta. O prognóstico para esta paciente foi considerado bom, uma vez que não havia indícios de anquilose da articulação temporomandibular e/ou manifestações neurológicas.

The complex of hyperostotic disorders is a rare and self-limiting condition, which has the same histophatological characteristics, which courses with non-neoplastic bone proliferations. It affects young dogs of different breeds, with variability the bones affected. The complex is composed of craniomandibular osteopathy, calvarial hyperostotic syndrome and hypertrophic osteodystrophy. It may be present in the bones of the skullcap, jaws, cervical spine and appendicular skeleton. The present report describes the condition of a female dog, American Bully breed, entire, three months old, with a complaint of painful swelling of the jaws, hyporexia and drooling for 15 days, presenting on physical examination, reduced amplitude and pain of the temporomandibular joint, bilateral firm thickening of the skull in the temporal fossa region, palpable firm-consistent thickening of the mandibles and respiratory crackle. After clinical evaluation and complementary tests, a presumptive diagnosis of hyperostotic disorders complex was reached. It was instituted pain management as a treatment, being effective for the maintenance of physiological needs until the patient reaches the adulthood. The prognosis for this patient was considered good, since there was no evidence of temporomandibular joint ankylosis and/or neurological manifestations.

Variation in facial bone growth remodeling in prehistoric populations from southern South America.

OBJECTIVES: To assess the intraspecific variation in bone remodeling patterns in modern humans, we studied two populations from southern South America that represent the extremes of morphological variation in this region. We particularly analyzed the ontogenetic changes in the patterns of bone growth remodeling and compared the patterns between samples. MATERIALS AND METHODS: We obtained high-resolution casts of the periosteal surface of the upper and middle face of subadults (n = 36) and adult (n = 36) individuals from a sample of hunter-gatherers from Patagonia and a sample of horticulturists from Northwest Argentina. The areas of bone formation and resorption were registered using an incident-light microscope. We then estimated the average bone remodeling map by sample and age, and performed principal component analysis and multivariate regressions to assess the extension and distribution of these areas across ontogeny and between samples. RESULTS: We found that the remodeling pattern of the glabella, supraorbital arch, frontal process of the maxilla, and a large part of the zygomatic bone is relatively constant in subadults and adults from both sample with a clear predominance of bone formation. In contrast, the middle face is characterized by the spatial alternation between formation and resorption areas, and greater variation with age and between samples. The main differences were found in areas related to chewing and muscle insertions. CONCLUSIONS: Our study provides the first evidence of interpopulation variation in bone growth remodeling and suggests that biomechanical factors can influence the observed patterns. It also underlines the need to account for ecological factors in within and between species comparisons.

Intraosseous hemangioma of the orbit

Intraosseous hemangioma is an extremely rare tumor that accounts for 1% or fewer of all osseous tumors. The most common sites of its occurrence are the vertebral column and calvaria. Occurrence in a facial bone is very rare. The authors aim to report a case of the surgical treatment of intraosseous hemangioma occurring in the periorbital region, which is a very rare site of occurrence and to introduce our own experiences with the diagnosis and treatment of this condition along with a literature review. A 73-year-old male patient visited our hospital with the chief complaint of a mass touching the left orbital rim. A biopsy was performed by applying a direct incision after local anesthesia. Eventually, intraosseous hemangioma was diagnosed histologically. To fully resect the mass, the orbital floor and zygoma were exposed through a subciliary incision under general anesthesia, and then the tumor was completely eliminated. Bony defect was reconstructed by performing a seventh rib bone graft. Follow-up observation has so far been conducted for 10 months after surgery without recurrence or symptoms.

The effect of light-emitting diode (590/830 nm)-based low-level laser therapy on posttraumatic edema of facial bone fracture patients.

PURPOSE: Posttraumatic edema in facial bone fracture patients may interfere with the operation field and delay the schedule. Thus, swiftly reducing the edema alleviates patient discomfort and advances the operation date. Ice packing and compression bandages are often used for such a purpose, but such methods are often inconvenient for the face. In this study, we aim to analyze the effect of light-emitting diode (LED) (590/830 nm)-based low-level laser therapy (LLLT) in posttraumatic edema in facial bone fracture patients. MATERIALS AND METHODS: We conducted a prospective cohort study of 40 patients who were admitted to a single institution for facial bone fracture. The patients were divided into two groups of 20 each, treated either with LLLT or with sham treatment light. We used an LLLT device that consists of planar LED-based arrays with double wavelengths 590 nm and 830 nm. The patients were treated with either true or sham light from posttraumatic day 1-5, twice a day. After each treatment, the volume of a patient's face was measured with a 3-dimensional camera. We analyzed and compared the changes in facial edema. The Wilcoxon rank sum test was conducted for statistical comparison of the two groups, and significance was set to the level of p < 0.05. RESULTS: The sex ratio and mean age of the two groups were of little difference. The fracture sites included the nasal bone, orbital wall, zygomaticomaxillary bone, mandible, and frontal sinus. Mechanisms of injury included fall, assault, traffic accident, sports, and gunshot. The total operation rate of both groups was equal to 85%. Our analysis showed a 16.5% reduction of edema in the LLLT group and 7.3% in the sham light group. The edema reduction was statistically significantly greater in the LLLT group than in the sham light group (p < 0.047). CONCLUSION: LED-based LLLT is recently receiving attention worldwide for its cost-effectiveness and large coverage area compared to traditional laser therapy. Recent studies support its effectiveness in various areas such as wound healing, skin rejuvenation, and pain alleviation. In this study, we treated facial bone fracture patients with LED-based LLLT, and showed its effectiveness in reducing posttraumatic edema.

Follicular thyroid carcinoma metastasis to the facial skeleton: a systematic review.

BACKGROUND: Follicular thyroid carcinoma (FTC) metastasis to the facial skeleton is exceedingly rare. A case of FTC metastasizing to the mandible is presented and a systematic review of the literature describing thyroid metastasis to the facial skeleton is performed. CASE PRESENTATION: A 73-year-old female presented with metastatic FTC to the mandible and underwent total thyroidectomy, segmental mandibulectomy, bone impacted fibular free flap reconstruction, and adjuvant radioactive iodine treatment. The PubMed database was searched for literature describing thyroid cancer with facial skeleton metastasis using the key words "thyroid," "cancer," "carcinoma," "metastasis," and "malignancy" with "oral cavity," "maxilla," "mandible," "sinus," "paranasal," and "orbit." Reports that only involved the soft tissues were excluded. Systematic review revealed 59 cases of well-differentiated thyroid cancer with facial skeleton metastasis: 35 mandibular metastases (21 = FTC), 6 maxilla metastases (2 = FTC), 9 orbital metastases (4 = FTC), and 11 paranasal sinus metastases (7 = FTC). Treatment included surgery, RAI, external beam radiotherapy (XRT), or a combination of these modalities. The one, two, and five-year survival rates were 100%, 79%, and 16%, respectively. CONCLUSION: Facial skeleton metastasis of FTC is a rare clinical challenge. Optimal treatment appears to include total thyroidectomy and resection of involved structures with or without adjuvant treatment.

Extending Genome-Wide Association Study Results to Test Classic Anthropological Hypotheses: Human Third Molar Agenesis and the "Probable Mutation Effect".

A genome-wide association study (GWAS) identifies regions of the genome that likely affect the variable state of a phenotype of interest. These regions can then be studied with population genetic methods to make inferences about the evolutionary history of the trait. There are increasing opportunities to use GWAS results-even from clinically motivated studies-for tests of classic anthropological hypotheses. One such example, presented here as a case study for this approach, involves tooth development variation related to dental crowding. Specifically, more than 10% of humans fail to develop one or more permanent third molars (M3 agenesis). M3 presence/absence variation within human populations has a significant genetic component (heritability estimate h 2 = 0.47). The evolutionary significance of M3 agenesis has a long history of anthropological speculation. First, the modern frequency of M3 agenesis could reflect a relaxation of selection pressure to retain larger and more teeth following the origins of cooking and other food-softening behaviors (i.e., the genetic drift hypothesis or, classically, the "probable mutation effect"). Alternatively, commensurate with increasing hominin brain size and facial shortening, M3 agenesis may have conferred an adaptive fitness advantage if it reduced the risk of M3 impaction and potential health complications (i.e., the positive selection hypothesis). A recent GWAS identified 70 genetic loci that may play a role in human M3 presence/absence variation. To begin evaluating the contrasting evolutionary scenarios for M3 agenesis, we used the integrated haplotype score (iHS) statistic to test whether those 70 genetic regions are enriched for genomic signatures of recent positive selection. None of our findings are inconsistent with the null hypothesis of genetic drift to explain the high prevalence of human M3 agenesis. This result might suggest that M3 impaction rates for modern humans do not accurately retrodict those of the preagricultural past. Alternatively, the absence of support for the positive selection hypothesis could reflect a lack of power; this analysis should be repeated following the completion of more comprehensive GWAS analyses for human M3 agenesis.

Adding Injury to Insult: A National Analysis of Combat Sport-Related Facial Injury.

OBJECTIVES/HYPOTHESIS: To estimate the incidence of patients presenting to emergency departments (EDs) for facial trauma sustained from participation in combat sports and evaluate injury patterns and patient demographics. METHODS: The National Electronic Injury Surveillance System (NEISS) was evaluated for facial injuries from wrestling, boxing, and martial arts leading to ED visits from 2008 to 2013. Relevant entries were examined for injury mechanism, location, type, as well as other patient characteristics. RESULTS: There were 1143 entries extrapolating to an estimated 42 395 ED visits from 2008 to 2013. Injury rates for boxing, marital arts, and wrestling were, respectively, 44, 56, and 120 injuries per 100 000 participants. Males comprised the majority (93.7%). A plurality of injuries involved lacerations (46.0%), followed by fractures (26.2%) and contusions/abrasions (19.3%). The proportion of fractures was highest among boxers (36.9%). Overall, the most common mechanisms of injury were punching, kicking, and head butting. CONCLUSIONS: The significant number of ED visits resulted from combat sports facial trauma, reinforcing the importance of familiarity with injury patterns among practitioners managing facial trauma. As most injuries involve individuals younger than 19 despite guidelines suggesting children and adolescents avoid combat sports, these findings may be used for patient education and encouragement of the use of personal protective equipment. Furthermore, injury patterns reported in this analysis may serve as an adjunct for enhancing clinical history taking and physical examination.

Antimicrobial activity of conventional and plant-extract disinfectant solutions on microbial biofilms on a maxillofacial polymer surface.

STATEMENT OF PROBLEM: Dentists often note problems with infection in patients with maxillofacial prostheses. Conventional disinfection protocols are not always effective and may alter the properties of the polymer used in the prosthesis. Thus, the search for improved disinfection methods is important. PURPOSE: The purpose of this in vitro study was to evaluate and compare the antimicrobial activity of conventional disinfectant solutions (water and neutral soap and 4% chlorhexidine) and plant extracts (Cymbopogon nardus and Hydrastis canadensis) on specimens of maxillofacial silicone contaminated with Candida albicans and Staphylococcus aureus biofilms. MATERIAL AND METHODS: Seventy-two silicone (MDX4-4210) specimens were fabricated (5×2 mm) and sterilized. Thirty-six were contaminated with C albicans (10(6) cells/mL) and 36 with S aureus (10(8) cells/mL) to evaluate the antimicrobial activity of the cleaning protocols. After incubation (37°C/72 hours), the specimens were divided into 5 groups: not disinfected (positive control), soaking in saline solution for 10 minutes, soaking in 4% chlorhexidine for 10 minutes, soaking in C nardus for 10 minutes, soaking in H canadensis for 10 minutes, and washing by hand with water and neutral soap for 30 seconds. The viability of cells was evaluated by XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and by scanning electron microscope analysis. The results were analyzed by ANOVA and the Tukey HSD test (α=.05). RESULTS: All disinfection solutions provided a statistically significant reduction in biofilm viability compared with the control group for both microorganisms (P<.05). Washing with water and neutral soap was significantly more effective in reducing biofilm viability than immersion in the disinfection solutions, with persistence of viable microorganisms between 1.05% for C albicans and 0.62% for S aureus after this cleaning protocol. Photomicrographs revealed that 4% chlorhexidine altered the surface of the polymer. CONCLUSIONS: Within the limitations of this in vitro study, it was concluded that the cleaning protocols with different disinfectant solutions produced a significant reduction in the viability of C albicans and S aureus biofilms on the silicone polymer. Washing with water and neutral soap was the most effective protocol against both microorganisms.

Long-term success of dental implant-supported dentures in postirradiated patients treated for neoplasms of the maxillofacial skeleton: a retrospective study.

OBJECTIVES: The reconstruction of oral function in irradiated patients with craniofacial tumors is a significant challenge. The aim of this study was to detect long-term success of dental implant-supported dentures in postirradiated patients treated for neoplasms of the maxillofacial skeleton. MATERIALS AND METHODS: From 2004 to 2011, 36 irradiated patients underwent oral function reconstruction using implant-supported prostheses. Bone augmentation was completed using vascularized bone grafts in 22 patients. Fourteen patients were treated by hyperbaric oxygen therapy (HBO). A total of 198 dental implants were used in jaw rehabilitation. After loading, implant success rates, biological and prosthetic complications, patient satisfaction, and psychological changes were recorded. RESULTS: Bone augmentation of the jaw was successful and vascularized grafts provided an additional vascular supply in compromised irradiated tissue. Rehabilitation was successful in all of the patients after loading. Thirty-eight dental implants failed, and 35 implants were removed. The success rate of the implants was 93.6 % for 10 years after loading. It was not a significant difference in implant success rate between the HBO group and the other groups. The prosthodontic maintenance results and complication rates showed that patients required intervention 0.19 times per year. All patients were satisfied with the oral restoration results. CONCLUSION: The restoration of oral function in radiotherapy patients with tumor resection using implant-supported prostheses is a viable treatment option. CLINICAL RELEVANCE: Either alone or in combination with HBO, dental implant-supported prostheses can be used an effective therapeutic approach for irradiated patients with oral function reconstruction.

Correction of Post-Traumatic Enophthalmos and Temporal Depression Using Rib Cartilage and Fat / 대한이비인후과학회지

Posttraumatic enophthalmos is one of the common complications of facial bone fracture, leading to serious functional and esthetic sequele. However, the correction of this complication is a challenging procedure. A 62-year old patient was injured in a traffic accident, resulting in enophthalmos of the right orbit, which had been uncorrected by a previous correction surgery. The patient showed prominent enophthalmos, ptosis of right orbit, and temporal area depression without complaining diplopia. Under general anesthesia, the correction of enophthalmos of right orbit was done using diced coastal cartilage and an absorbable mesh plate. The depressed right temporal and the frontal area were reinforced using harvested abdominal fat. Three months after the surgery, additional fat injection was introduced to supplement under local anesthesia. Currently, 12 months after the surgery, the patient is in stable state without any complications.

Pre-clinical in vivo models for the screening of bone biomaterials for oral/craniofacial indications: focus on small-animal models.

Preclinical in vivo experimental studies are performed for evaluating proof-of-principle concepts, safety and possible unwanted reactions of candidate bone biomaterials before proceeding to clinical testing. Specifically, models involving small animals have been developed for screening bone biomaterials for their potential to enhance bone formation. No single model can completely recreate the anatomic, physiologic, biomechanic and functional environment of the human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions and handling are discussed in this paper to elucidate the advantages and disadvantages of small-animal models. Model selection should be based not on the 'expertise' or capacities of the team, but rather on a scientifically solid rationale, and the animal model selected should reflect the question for which an answer is sought. The rationale for using heterotopic or orthotopic testing sites, and intraosseous, periosseous or extraskeletal defect models, is discussed. The paper also discusses the relevance of critical size defect modeling, with focus on calvarial defects in rodents. In addition, the rabbit sinus model and the capsule model in the rat mandible are presented and discussed in detail. All animal experiments should be designed with care and include sample-size and study-power calculations, thus allowing generation of meaningful data. Moreover, animal experiments are subject to ethical approval by the relevant authority. All procedures and the postoperative handling and care, including postoperative analgesics, should follow best practice.

Future and training of craniofacial surgery in India.

Craniofacial surgery, in the strictest sense, is the surgery of structures above and behind the maxilla. Craniofacial surgery is not new to India and has been around for more than 4 decades now since the 1970s. Keeping in mind the promotion of the specialty in India, an Indian Craniofacial Foundation was launched in the year 2012 at the Annual Meeting of the Association of Plastic Surgeons of India. To develop a craniofacial center in India, the primary requirement is a source of funding. Several craniofacial centers, which are already running successfully in India, have amply demonstrated that this can be done in several ways. We would like to discuss here the 2 models of craniofacial service delivery and training that the authors have seen and experienced firsthand.

Injuries associated with combat sports, active component, U.S. Armed Forces, 2010-2013.

The practice of combat sports creates a potential for training- and sports-related injuries among military members. During the 4-year surveillance period, there were 12,108 cases of injuries associated with combat sports among active component service members; the overall incidence rate was 21.0 per 10,000 person-years (p-yrs). The rates were higher among service members who were male, Hispanic, in the youngest age groups, in the Army, junior enlisted, and in combat-specific occupations. The rate among recruit/ trainees (779.4 per 10,000 p-yrs) was more than 165 times the rate among all other active component service members (non-recruits) (4.7 per 10,000 p-yrs). Sprains, strains, and contusions accounted for more than one-half of the primary (first-listed) diagnoses associated with combat sports cases. More serious conditions such as concussions/head injuries and skull/face fractures/intracranial injuries were reported among 3.9% and 2.1% of all cases and were more common among boxing-related cases. Hand/wrist fractures were also common among boxing cases. Wrestling had comparatively greater proportions of dislocations and open wounds. Although the combat sport training provides many physical and mental benefits to the individual, safety practices should be enforced to reduce the most frequent and serious injuries.

Tratamento cirúrgico da paquidermoperiostose primária - relato de dois casos / Surgical Treatment of Primary Pachydermoperiostosis: Report of Two Cases / Surgical Treatment of Primary Pachydermoperiostosis: Report of Two Cases

A paquidermoperiostose primária é uma doença rara, caracterizada por aposição excessiva do periósteo do crânio, coexistindo com espessamento da epiderme e derme (paquidermia), provocando deformidades grosseiras. Devido à diversidade de estruturas acometidas, há várias opções cirúrgicas e métodos complementares que são utilizados no tratamento das alterações faciais desses pacientes. Esse trabalho apresenta o lifting subperiosteal como uma opção de tratamento estético para a face de pacientes portadores dessa síndrome, através do relato de dois casos operados no Hospital das Clínicas da Universidade Federal de Minas Gerais.

Primary pachydermoperiostosis is a rare disease characterized by excessive skull affixing of the periosteum, coexisting with thickening of the epidermis and dermis (pachydermia), thereby causing gross deformities. Owing to the variety of affected structures, there are several surgical options and complementary methods that are used in the treatment of facial alterations in these patients. This report describes the use of subperiosteal detachment as an aesthetic treatment option for the faces of two patients with primary pachydermoperiostosis, operated at the Hospital das Clínicas of the Federal University of Minas Gerais.

Sistema miofuncional orofacial e trauma de face: revisão crítica da literatura / Changes in the orofacial myofunctional system after treatment for facial trauma: a critical review of the literature

Introdução: Esta revisão qualitativa da literatura levantou publicações científicas internacionais sobre a funcionalidade do sistema miofuncional orofacial nos traumas faciais, por meio da base de dados PubMed. Método: O levantamento realizado limitou-se a seres humanos, de qualquer faixa etária, no idioma inglês, entre os anos de 2005 e 2011. As publicações sem acesso completo, repetidas por sobreposição das palavras chave, estudos de caso, revisões de literatura, cartas ao editor e as não relacionadas diretamente ao tema foram excluídas. Resultados: Foram identificados 831 estudos, sendo 14 dentro dos critérios estabelecidos. Notou-se que a avaliação mais frequente foi a da função mandibular e depois análise de tratamentos; ocorreu mais fratura no côndilo que ângulo mandibular; utilizou-se mais tratamento cirúrgico juntamente com o conservador, seguido pelo somente cirúrgico e finalmente somente conservador; a maior incidência de traumas faciais foi em adultos do sexo masculino; poucas pesquisas foram realizadas com crianças e grupo-controle; utilizaram-se mais avaliações da função mandibular e clínicas, na maioria pré e pós-cirurgia; a força de mordida e a área oclusal apresentaram melhora póstratamento, no entanto a assimetria mandibular permaneceu; os valores de abertura máxima da boca atingiram a normalidade, porém inferiores ao grupo-controle; houve persistência de alterações na mobilidade mandibular e dor, mesmo após o tratamento; e a terapia miofuncional melhorou o quadro de alterações. Conclusão: É necessário mais publicações sobre o tratamento fonoaudiológico baseado na abordagem miofuncional orofacial nos traumas faciais.

Introduction: This qualitative literature review aims to highlight international scientific publications selected from the PubMed database that describe the changes in the function of the orofacial myofunctional system after facial trauma and the associated treatment outcomes. Methods: Studies published in English between 2005 and 2011 and including individuals of all age groups were included in this review. Publications that were not open access, studies appearing more than once because of overlapping keywords, case studies, literature reviews, letters to the editor, and studies that were not directly related to the subject were excluded. Results: A total of 831 studies were identified, 14 of which fulfilled the established criteria. Assessment of jaw function was the most frequent evaluation performed in the included studies, followed by the analysis of treatments. The incidence of condylar fractures was higher than that of mandibular angle fractures. The majority of cases were managed by surgery combined with conservative treatment, followed by surgery alone and conservative treatment alone. Adult men exhibited a higher incidence of facial trauma. Few studies included children or control groups. Further assessment of jaw and clinical functions before and after surgery revealed the following findings. The bite force and occlusal contact area improved after treatment, whereas mandibular asymmetry persisted even after surgery. The maximum mouth opening returned to normal after treatment, although the range of mouth opening was lower in patients with facial trauma than in controls. Persistent mobility in the mandibular teeth and pain were observed even after treatment. Myofunctional therapy resulted in an overall improvement in jaw function. Conclusions: Although the number of studies on facial trauma is increasing, few studies address the use and benefits of orofacial myofunctional therapy in this field. Further studies on orofacial myofunctional therapy combined with surgery and/ or conservative treatment for facial trauma are necessary.

Craniofacial variation, body size and ecological factors in aboriginal populations from central Patagonia (2000-200 years B.P.).

Previous studies have shown that ecological factors had a significant role in shaping the patterns of craniofacial variation among South American populations. Here, we evaluate whether temperature and diet contributed to facial diversification in small geographic areas. Facial size and shape of 9 osteological samples from central Patagonia (Argentina) were described using 2D landmarks and semilandmarks. Data on mean annual temperature, diet composition (δ(13)C and δ(15)N values) and femoral head maximum breadth, used as a proxy of body mass, were obtained for each sample. We then tested the association of body mass and the ecological variables with facial morphology using spatial regression techniques and a model selection approach. Akaike Information Criterion produced disparate results for both components of facial morphology. The best model for facial size included temperature and body mass proxy, and accounted for more than 80% of variation in size. Lower temperatures were related to larger facial sizes. Body mass was negatively associated with facial size and showed no relationship with the temperature. This suggests a relatively independent variation of cranial traits and body mass at the spatial scale studied here. Facial shape was not associated with the temperature or diet composition, contrasting with the patterns observed at larger spatial scales. Our results point out that the effect of climatic variables on cranial traits might be a source of morphological differentiation not only at large scales but also in small geographic areas, and that size and shape display a differential preservation of environmental signals.

Fibrous dysplasia of bone associated with primary hyperparathyroidism.

OBJECTIVE: Fibrous dysplasia of bone and primary hyperparathyroidism (PHPT) may occur in patients with McCune-Albright Syndrome. A small number of cases with both diagnoses that are not associated with the above-mentioned genetic disorder have been published in the literature. It is uncertain if these disorders are linked in some way. In the present study, we aimed to further explore a potential relationship between PHPT and fibrous dysplasia of bone. METHODS: We conducted a retrospective review of all cases seen at Mayo Clinic, Rochester, Minnesota, between 1976 and 2011 that were diagnosed with both PHPT and fibrous dysplasia of bone. RESULTS: We identified 10 patients who were diagnosed with both PHPT and fibrous dysplasia of bone. Fibrous dysplasia was polyostotic in 7 (70%) cases. It affected the lower extremities in 6 (60%) patients, the skull or facial bones in 4 (40%), and was localized to one rib in 1 patient (10%). In 4 patients, fibrous dysplasia was diagnosed first, between 9 to 50 years before being diagnosed with PHPT. Two cases of fibrous dysplasia were recognized between 2 and 5 years after the diagnosis of PHPT. The remaining 4 patients were diagnosed with both conditions at approximately the same time. CONCLUSION: It remains unclear if the association between fibrous dysplasia of bone and PHPT is more than coincidental, although the possibility of a rare familial genetic syndrome is not completely excluded.

Duplicated zebrafish co-orthologs of parathyroid hormone-related peptide (PTHrP, Pthlh) play different roles in craniofacial skeletogenesis.

In mammals, parathyroid hormone-related peptide (PTHrP, alias PTH-like hormone (Pthlh)) acts as a paracrine hormone that regulates the patterning of cartilage, bone, teeth, pancreas, and thymus. Beyond mammals, however, little is known about the molecular genetic mechanisms by which Pthlh regulates early development. To evaluate conserved pathways of craniofacial skeletogenesis, we isolated two Pthlh co-orthologs from the zebrafish (Danio rerio) and investigated their structural, phylogenetic, and syntenic relationships, expression, and function. Results showed that pthlh duplicates originated in the teleost genome duplication. Zebrafish pthlha and pthlhb were maternally expressed and showed overlapping and distinct zygotic expression patterns during skeletal development that mirrored mammalian expression domains. To explore the regulation of duplicated pthlh genes, we studied their expression patterns in mutants and found that both sox9a and sox9b are upstream of pthlha in arch and fin bud cartilages, but only sox9b is upstream of pthlha in the pancreas. Morpholino antisense knockdown showed that pthlha regulates both sox9a and sox9b in the pharyngeal arches but not in the brain or otic vesicles and that pthlhb does not regulate either sox9 gene, which is likely related to its highly degraded nuclear localization signal. Knockdown of pthlha but not pthlhb caused runx2b overexpression in craniofacial cartilages and premature bone mineralization. We conclude that in normal cartilage development, sox9 upregulates pthlh, which downregulates runx2, and that the duplicated nature of all three of these genes in zebrafish creates a network of regulation by different co-orthologs in different tissues.