SHORT Syndrome: Systematic Appraisal of the Medical and Dental Phenotype.

INTRODUCTION: SHORT syndrome is a rare autosomal dominant condition described by its acronym of short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger abnormality, and teething delay. Individuals have a distinct progeroid craniofacial appearance with a triangular face, frontal bossing, hypoplastic or thin alae nasi, large low-set ears, and mandibular retrognathia. OBJECTIVES: To systematically appraise the literature and update the clinical phenotype with emphasis on the dental condition. DESIGN: A systematic literature search was carried out to update the clinical phenotype, identifying reports of individuals with SHORT syndrome published after August 2015. The same search strategy but not limited to publication date was carried out to identify reports of the dental phenotype. Two independent reviewers screened 1937 articles with 55 articles identified for full-text review. RESULTS: Nineteen individuals from 11 families were identified. Facial dysmorphism including ocular depression, triangular shaped face, frontal bossing, large low-set ears, and micrognathia were the most consistent features followed by lipodystrophy, insulin resistance, and intrauterine growth restriction. Teething delay, microdontia, hypodontia, and enamel hypoplasia have all been reported. CONCLUSION: Features that comprise the SHORT acronym do not accurately or completely describe the clinical phenotype. The craniofacial appearance is one of the most consistent features. Lipodystrophy and insulin resistance may also be considered cardinal features. After teething delay, enamel hypoplasia and microdontia are the most common dental manifestations. We present recommendations for the dental and orthodontic/orthognathic management of individuals with SHORT syndrome.

Maxillary Changes Following Facial Bipartition - A Three-Dimensional Quantification.

INTRODUCTION: Children with Apert syndrome have hypertelorism and midfacial hypoplasia, which can be treated with facial bipartition (FB), often aided by rigid external distraction. The technique involves a midline osteotomy that lateralizes the maxillary segments, resulting in posterior cross-bites and midline diastema. Varying degrees of spontaneous realignment of the dental arches occurs postoperatively. This study aims to quantify these movements and assess whether they occur as part of a wider skeletal relapse or as dental compensation. METHODS: Patients who underwent FB and had high quality computed tomography scans at the preoperative stage, immediately postsurgery, and later postoperatively were reviewed. DICOM files were converted to three-dimensional bone meshes and anatomical point-to-point displacements were quantified using nonrigid iterative closest point registration. Displacements were visualized using arrow maps, thereby providing an overview of the movements of the facial skeleton and dentition. RESULTS: Five patients with Apert syndrome were included. In all cases, the arrow maps demonstrated initial significant anterior movement of the frontofacial segment coupled with medial rotation of the orbits and transverse divergence of the maxillary arches. The bony position following initial surgery was shown to be largely stable, with primary dentoalveolar relapse correcting the dental alignment. CONCLUSIONS: This study showed that spontaneous dental compensation occurs following FB without compromising the surgical result. It may be appropriate to delay active orthodontic for 6-months postoperatively until completion of this early compensatory phase.

Surgical Correction of Craniofacial Microsomia: Evaluation of Interventions in 565 Patients at Three Major Craniofacial Units.

BACKGROUND: Craniofacial microsomia is characterized by an asymmetric hypoplasia of derivatives of the first and second pharyngeal arch, leading to a variety of phenotypic presentations. Studies on surgical correction of patients with craniofacial microsomia have small cohorts, leaving controversial opinions on the optimal treatment modality, the indication for surgery, and the optimal timing of surgery. The purpose of this study was to evaluate the types of, timing of, and total number of surgical corrections performed and the number of surgical procedures in correlation to the severity of the phenotype. METHODS: A retrospective chart study was conducted including patients diagnosed with craniofacial microsomia from three large craniofacial units. Demographic, radiographic, and clinical information was obtained, including type and number of surgical procedures and age at the time of surgery. RESULTS: A total of 565 patients were included. In total, 443 (78.4 percent) of all patients underwent some form of surgery during their life, varying from skin tag removal to major craniofacial operations. The number of surgical interventions was higher with increasing severity of phenotype, bilateral presentation, and a younger age at the first intervention. CONCLUSIONS: Multiple surgical corrections are frequently seen in patients with a more severe or bilateral presentation. Furthermore, those who are treated earlier in life for correction of asymmetry of the mandible will undergo significantly more surgical procedures to correct the asymmetry later on, independent of the Pruzansky-Kaban type mandible. A prospective international multicenter study is designed with a uniform registration and outcome measurement tool to identify the optimal treatment strategy.

Correcting Exorbitism by Monobloc Frontofacial Advancement in Crouzon-Pfeiffer Syndrome: An Age-Specific, Time-Related, Controlled Study.

BACKGROUND: In FGFR2 craniosynostosis, midfacial hypoplasia features oculo-orbital disproportion and symptomatic exorbitism. Clinical consequences may mandate surgery at a young age to prevent globe subluxation, corneal ulceration, and potential loss of vision. Monobloc osteotomy and distraction osteogenesis (monobloc distraction) seek to correct exorbitism. A report of the age-related impact of monobloc osteotomy and distraction osteogenesis on orbital volume, globe volume, and globe protrusion is presented. METHODS: Computed tomographic scan data from 28 Crouzon-Pfeiffer patients were assessed at preoperative, early postoperative, and 1-year follow-up time points. Orbital volumes, globe volumes, and globe protrusions were measured by manual and semiautomatic segmentation techniques, and these were compared to 40 age-matched controls. RESULTS: Crouzon-Pfeiffer syndrome orbital volumes are significantly small, and are significantly overexpanded by distraction to endpoints correcting symptomatic exorbitism. Globe volumes are significantly larger than controls under 5 years, do not independently correlate with globe protrusion, and are unaffected by surgery. Correlation between orbital volume expansion and reduction of globe protrusion is not significant. Age-related variations of postoperative growth potential occur to 1 year postoperatively. The Crouzon-Pfeiffer syndrome FGFR2 orbit exhibits early growth acceleration followed by premature growth arrest at 10 to 14 years. CONCLUSIONS: Orbital volume expansion by monobloc osteotomy and distraction osteogenesis is not the sole determinant of reduced globe protrusion. Mean volume relapse of the orbit at 1 year is insignificant across the series. Derived Crouzon-Pfeiffer growth curves suggest that "early functional monobloc" in infants occurs on a background of dynamic orbital growth, which remains programmed to a Crouzon-Pfeiffer FGFR2 phenotype and aligns with the incidence of delayed clinical regression and later secondary surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Craniofacial and extracraniofacial anomalies in craniofacial microsomia: a multicenter study of 755 patients'

PURPOSE: Craniofacial microsomia (CFM) is a congenital malformation of structures derived from the first and second pharyngeal arches leading to underdevelopment of the face. However, besides the craniofacial underdevelopment, extracraniofacial anomalies including cardiac, renal and skeletal malformation have been described. The aim of this study is to analyse a large population of patients with regard to demographics, typical phenotypes including craniofacial and extracraniofacial anomalies, and the correlations between the different variables of this condition. MATERIAL AND METHODS: A retrospective study was conducted in patients diagnosed with CFM with available clinical and/or radiographic images. All charts were reviewed for information on demographic, radiographic and diagnostic criteria. The presence of cleft lip/palate and extracraniofacial anomalies were noted. Pearson correlation tests and principal component analysis was performed on the phenotypic variables. RESULTS: A total of 755 patients were included. The male-to-female ratio and right-to-left ratio were both 1.2:1. A correlation was found among Pruzansky-Kaban, orbit and soft tissue. Similar correlations were found between ear and nerve. There was no strong correlation between phenotype and extracraniofacial anomalies. Nevertheless, extracraniofacial anomalies were more frequently seen than in the 'normal' population. Patients with bilateral involvement had a more severe phenotype and a higher incidence of extracraniofacial and cleft lip/palate. CONCLUSION: Outcomes were similar to those of other smaller cohorts. Structures derived from the first pharyngeal arch and the second pharyngeal arch were correlated with degree of severity. Extracraniofacial anomalies were positively correlated with CFM. The findings show that bilaterally affected patients are more severely affected and should be approached more comprehensively.

Supernumeraries in Nicolaides-Baraitser Syndrome.

BACKGROUND: Nicolaides-Baraitser Syndrome(NCBRS) is an extremely rare condition which has been reported in only a few cases. NCBRS is a distinct clinical condition with typical clinical features of pre- and post-natal global developmental delay, impaired speech, and seizures. Microcephaly, sparse hair, anteverted alae nasi, undefined philtrum, prominence of distal phalanges and interphalangeal joints, and short metacarpals are also typical of NCBRS. CASE REPORT: There are no reported cases in the literature of patients with NCBRS presenting with multiple dental impactions, and to the authors' knowledge, this is the 28th fully documented case of NCBRS and only 75 cases identified as potentially having NCBRS. The clinical features, diagnosis, and course of management are also described. CONCLUSION: Although NCBRS is very rare, it is important to assess dental development in view of the possibility of multiple supernumerary teeth which can have detrimental effects on the occlusion.

Fronto-facial advancement and bipartition in Crouzon-Pfeiffer and Apert syndromes: Impact of fronto-facial surgery upon orbital and airway parameters in FGFR2 syndromes.

A major concern in FGFR2 craniofaciosynostosis is oculo-orbital disproportion, such that orbital malformation provides poor accommodation and support for the orbital contents and peri-orbita, leading to insufficient eyelid closure, corneal exposure and eventually to functional visual impairment. Fronto-facial monobloc osteotomy followed by distraction osteogenesis aims to correct midfacial growth deficiencies in Crouzon-Pfeiffer syndrome patients. Fronto-facial bipartition osteotomy followed by distraction is a procedure of choice in Apert syndrome patients. These procedures modify the shape and volume of the orbit and tend to correct oculo-orbital disproportion. Little is known about the detailed 3D shape of the orbital phenotype in CPS and AS, and about how this is modified by fronto-facial surgery. Twenty-eight patients with CMS, 13 patients with AS and 40 control patients were included. CT scans were performed before and after fronto-facial surgery. Late post-operative scans were available for the Crouzon-Pfeiffer syndrome group. Orbital morphology was investigated using conventional three-dimensional cephalometry and shape analysis after mesh-based segmentation of the orbital contents. We characterized the 3D morphology of CPS and AS orbits and showed how orbital shape is modified by surgery. We showed that monobloc-distraction in CPS and bipartition-distraction in AS specifically address the morphological characteristics of the two syndromes.

Preharvest Salmonella Detection for Evaluation of Fresh Ground Poultry Product Contamination.

Salmonella is an important economic and public health concern for the poultry industry. Fresh ground product has been linked with multiple salmonellosis outbreaks in humans. Exposure can be controlled by proper handling and preparation by consumers; however, the industry desires to minimize carriage levels in the final product. A substantial obstacle in reducing product contamination stems from limitations in diagnostic methodologies. Detection of Salmonella contamination currently requires extended incubation periods, and by the time test results are available, the fresh product has reached retail shelves. The goal of this study was to develop a preharvest diagnostic protocol for the evaluation of ground product contamination. The turkey processing plant where this research was conducted had previously established Salmonella screening (BAX system) of ground product, thus providing an opportunity for preharvest sample comparison. Drag swabs were collected from live-haul trailers entering the processing plant over a 12-month period. The swabs were added to modified buffered peptone water and incubated at 40°C. After incubation for 6 h or overnight, samples were tested for the presence of Salmonella with the DNAble assay and related to ground turkey samples from corresponding lots. The linear relationship for the percentage of Salmonella-positive live-haul trailers was significant for both the 6-h (slope = 1.02, R(2) = 0.96, and P < 0.0001) and overnight (slope = 0.35, R(2) = 0.93, and P = 0.0015) incubations, with the percentage of Salmonella-positive ground turkey samples. These data indicate that preharvest screening provides a meaningful evaluation of product contamination. Additionally, the 6-h incubation protocol is rapid enough to allow for product mitigation and could potentially aid in the reduction of future salmonellosis outbreaks.

Correcting the typical Apert face: combining bipartition with monobloc distraction.

BACKGROUND: Bipartition distraction is a novel procedure combining frontofacial bipartition and monobloc distraction. Apert syndrome and other syndromic craniofacial dysostoses are often characterized by hypertelorism, with a negative canthal axis and counterrotated orbits. Central midface hypoplasia can result in a biconcave face in both midsagittal and axial planes. Bipartition distraction can correct these facial abnormalities. METHODS: Twenty patients (19 Apert syndrome patients and one Pfeiffer syndrome patient, aged 1.6 to 21 years) underwent bipartition distraction. Severity of appearance was graded preoperatively and postoperatively as mild, moderate, or severe. Functional problems were documented by a multidisciplinary team. Central and lateral midface skeletal advancement were measured. Follow-up ranged from 15 months to 7 years. RESULTS: Bipartition distraction consistently produced more central than lateral facial advancement. Mean central advancement was 13.2 ± 5.9 mm at sella-nasion and 11.7 ± 5.4 mm at sella-A point. Lateral advancement was 4.7 ± 2.8 mm. Unbending the face improved aesthetic appearance. Airway function, eye exposure, and elevated intracranial pressure were improved. Complications included six temporary cerebrospinal fluid leaks (four needing a lumbar drain), five patients with postoperative seizures, five patients requiring Rigid External Distraction frame repositioning, one palatal fistula, one velopharyngeal incompetence, five pin-site infections, one abscess under frontal bone, three cases of sepsis, nine patients with worsened strabismus, two patients with enophthalmos, one patient with partial visual field loss, and three patients who required reintubation because of aspiration. CONCLUSIONS: : Bipartition distraction is an effective procedure with which to differentially advance the central face in Apert syndrome. It improves both function and aesthetics. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, IV.

Complications of frontofacial advancement.

PURPOSE: The purpose of this study was to document the early and late complications associated with frontofacial distraction. METHOD: A systematic review of the literature on complications in craniofacial surgery and a review of records of patients undergoing frontofacial distraction at Great Ormond Street Hospital for Children over a 10-year period were conducted. RESULTS: Complications arising from frontofacial advancement are common. Mortality rates varied between 0 and 4.5 %. There has been a general decline in reported mortality rates with time, and the most recent series report mortalities of less than 1 %. The incidence of significant blood loss (greater than one blood volume) in patients undergoing monobloc osteotomy varied between 5.3 and 9.1 %. CSF leaks following monobloc distraction are common (incidence, 2-20 %). Most of these leaks settle spontaneously. The incidence of frontal bone flap necrosis requiring debridement and a subsequent cranioplasty varied between 3 and 20 %. CONCLUSIONS: The functional and aesthetic benefits of frontofacial distraction are well documented, but these advantages are associated with a significant complication rate. The potential benefits of frontofacial distraction need to be carefully weighed against the potential complications when deciding to recommend surgery.

Prevalence of abnormal pattern reversal visual evoked potentials in craniosynostosis.

BACKGROUND: The purpose of this study was to examine the prevalence and type of changes observed in the pattern reversal visual evoked potentials recorded at the first assessment of children with craniosynostosis. METHODS: Visual evoked potentials were recorded from 114 patients with craniosynostosis. Eighty-one patients were syndromic and 33 were nonsyndromic. No patient had received any craniofacial surgical intervention. At the time of the test, 22 of 40 patients were aged 6 months and younger, and 18 patients were between 6 months and 1 year of age. Pattern reversal visual evoked potentials were recorded from a midoccipital electrode positioned 3 cm above the inion. The pattern reversal visual evoked potentials elicited to 50' checks with three reversals per second viewed with both eyes were analyzed for n80-p100 amplitude, p100 latency, and breadth of waveform. RESULTS: Sixty percent of patients had abnormal pattern reversal visual evoked potentials to 50' checks. This did not show a significant association with age, or classification of craniosynostosis. CONCLUSIONS: The high prevalence of abnormal pattern reversal visual evoked potentials to a robust stimulus suggests that visual pathway dysfunction, as measured electrophysiologically, can affect a majority of patients with craniosynostosis. This study indicates that a baseline evaluation of all children with craniosynostosis at their first presentation is essential if subsequent electrophysiologic visual pathway monitoring is to take place.

Identification of new morphological and life-cycle stages of Cochlosoma anatis and experimental transmission using pseudocyst.

Cochlosoma anatis is a flagellated intestinal parasite that infects a variety of avian species. C. anatis infections have been associated with decreased weight gain and increased morbidity and mortality. Conditions favoring the growth of this organism in birds are current pathogenic intestinal infections and/or young age. There is little data describing the life cycle of this parasite. In this study, electron microscopy images are presented that document longitudinal binary fission of the trophozoite stage and outline the events of pseudocyst formation, which includes a rounding stage. Evidence provided here indicates that the pseudocyst stage may be a mechanism for transmission of this organism. The observations reported here provide additional evidence of homology between Cochlosoma and members of the trichomonad order.

An in vitro study into the corrosion of intra-oral magnets in the presence of dental amalgam.

The aim of this investigation was to study the corrosion behaviour and products of uncoated neodymium-iron-boron magnets in the presence of dental amalgam. Microcosm plaques were grown on discs of neodymium-iron-boron magnets or amalgam in a constant depth film fermentor. The biofilms were supplied with artificial saliva and growth was determined by viable counting. The results showed that the neodymium-iron-boron magnets corroded with an average daily weight loss of 0.115 +/- 0.032 per cent. However, when the magnets were in close proximity to the amalgam the amount of corrosion was reduced to a daily loss of 0.066 +/- 0.023 per cent. The highest loss of constituent elements from the corrosion products of the magnets was observed for iron. The composition of the microcosm plaques altered markedly between the two materials with less streptococci and more Veillonella spp. present in the biofilms grown on magnets in the presence of amalgam. The corrosion of neodymium-iron-boron magnets is limited and in the presence of amalgam is reduced further. This suggests that amalgam present in the mouth will not cause an increased clinical risk in terms of biocompatibility with neodymium-iron-boron magnets.

Toward pathogenesis of Apert cleft palate: FGF, FGFR, and TGF beta genes are differentially expressed in sequential stages of human palatal shelf fusion.

OBJECTIVE: Critical cellular events at the palatal medial edge epithelium (MEE) occur in unperturbed mammalian palatogenesis, the molecular control of which involves a number of growth factors including transforming growth factor beta 3 (TGF beta 3). Apert syndrome is a monogenic human disorder in which cleft palate has been significantly correlated to the fibroblast growth factor receptor (FGFR) 2-Ser252Trp mutation. We report the relative expression of these genes in human palatogenesis. METHODS: The expression of the IgIIIa/b and IgIIIa/c transcript isoforms of FGFR2 and the proteins FGFR1, FGFR2, and FGFR3 was studied in situ throughout the temporospatial sequence of human palatal shelf fusion and correlated with the expression of TGF beta 3. In addition, the immunolocalization of the ligand FGFs 2, 4, and 7 was undertaken together with the intracellular transcription factor STAT1, which is activated by FGFR signaling. RESULTS: FGFRs are differentially expressed in the mesenchyme and epithelia of fusing palatal shelves, in domains overlapping those of their ligands FGF4 and FGF2 but not FGF7. Coexpression is seen with TGF beta 3, which is implicated in MEE dynamics and FGF and FGFR upregulation, and STAT1, an intracellular transcription factor that mediates apoptosis. CONCLUSIONS: The coregulation of molecules of the FGFR signaling pathway with TGF beta 3 throughout the stages of human palatal fusion suggests their controlling influence on apoptosis and epitheliomesenchymal transdifferentiation at the MEE. Experimental evidence links FGFR2-IgIIIa/b loss of function with palatal clefting, and these correlated data suggest a unique pathological mechanism for Apert cleft palate.

Field evaluation of tylosin premix in layers previously vaccinated with a live Mycoplasma gallisepticum vaccine.

Mycoplasma gallisepticum infection results in numerous clinical signs including a reduction in egg production in laying chickens. Attempts to prevent mycoplasmosis have included vaccination with both killed and attenuated live M. gallisepticum strains. Live vaccines provide reduction in clinical signs and have been shown to replace indigenous strains when used in a consistent program for several placements. Antibiotic therapy is another option for controlling losses associated with mycoplasmosis. Therapeutic antibiotics with activity against mycoplasma approved for use in poultry include tetracyclines and tylosin. These drugs also are approved for feed efficiency when administered in the feed at levels below the therapeutic index for mycoplasma. The data presented here suggest that birds vaccinated with the live 6/85 strain of M. gallisepticum and then fed tylosin, at the approved level for feed efficiency, exhibit a serologic vaccine response similar to that of unmedicated birds but show improved feed efficiency.