Evaluation of tooth size in non-syndromic cleft lip and palate patients: A retrospective Italian study.

AIM: This study aims to evaluate the dental dimension in cleft lip and palate patients presenting agenesis of at least an upper lateral incisor and to compare the results with those of two control groups. A control group consisted of general orthodontic patients without agenesis, while the other group consisted of orthodontic patients with agenesis of at least one upper lateral incisor. METHODS: Records of 40 (30 male, 10 female) cleft lip and palate patients (Group A), 40 (17 male, 23 female) patients representing the control group of general orthodontic patients (Group B) and 40 patients (14 male, 26 female) with at least one missing lateral incisor (Group C) were collected and analysed. Mesiodistal tooth size of all teeth (except second and third molars) was measured on digital or plaster dental casts. RESULTS: Tooth size in cleft lip and palate patients (Group A) was similar to that of the control group (Group B) of general orthodontic patients without tooth agenesis, except for the upper central incisors and the second upper left bicuspids that presented a significant reduction in the mesiodistal dental width. Non-syndromic patients with at least one missing upper lateral incisor showed a significant reduction of mesiodistal tooth size compared to Group A and to Group B. CONCLUSION: Dental width of cleft lip and palate patients is similar to that of a normal orthodontic population, with the exception of the upper central incisor and upper premolars on one side.

Impact of COVID-19 epidemic on maxillofacial surgery in Italy.

Maxillofacial departments in 23 surgical units in Italy have been increasingly involved in facing the COVID-19 emergency. Elective surgeries have been progressively postponed to free up beds and offer human and material resources to those infected. We compiled an inventory of 32 questions to evaluate the impact of the SARS-COV2 epidemic on maxillofacial surgery in 23 selected Italian maxillofacial departments. The questionnaire focused on three different aspects: the variation of the workload, showing both a reduction of the number of team members (-16% among specialists, -11% among residents) due to reallocation or contamination and a consistent reduction of elective activities (the number of outpatient visits cancelled during the first month of the COVID-19 epidemic was about 10 000 all over Italy), while only tumour surgery and trauma surgery has been widely guaranteed; the screening procedures on patients and physicians (22% of maxillofacial units found infected surgeons, which is 4% of all maxillofacial surgeons); and the availability of Personal Protective Equipment, is only considered to be partial in 48% of Maxillofacial departments. This emergency has forced those of us in the Italian health system to change the way we work, but only time will prove if these changes have been effective.

Study of ABCB1 multidrug resistance protein in a common orofacial malformation.

The onset of embryonic malformations is greatly determined by the intrauterine environment, conditioned by maternal lifestyle, diet, drugs and medication intake, in addition to both foetal and maternal genotypes. Maternal C677T MTHFR genotype has been identified as important factor in cleft lip with or without cleft palate (CL/P) etiology. In the present study we evaluated the possible interaction between maternal methylenetetrahydrofolate reductase (MTHFR) and foetal ABCB1 genotypes. ABCB1 gene codes for a drug-transport pump in charge to protect the cell by extruding a variety of harmful exogens, but with a reduced activity in a folate-restricted condition. Maternal 677T genotype is translated in a reduced folate availability for the developing embryo who consequently may becomes more exposed to external insults. A family based association analysis was performed to test the effect of ABCB1 polymorphisms in clefting, in the whole sample and in the stratified sample accordingly to maternal MTHFR genotype. No evidence of association between ABCB1 polymorphisms and CL/P was detected. This suggests that ABCB1 or ABCB1-MTHFR feto-maternal interaction could have no effect in orofacial clefting or could play a role in a limited number of cases.

Evidence of an involvement of TFAP2A gene in non-syndromic cleft lip with or without cleft palate: an Italian study.

Unraveling of factors involved in multifactorial diseases is a great challenge. Different approaches can be contemplate and applied to a variety of congenital malformations. In the present investigation TFAP2A has been considered a good candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) aetiology, basing on a sum of considerations. TFAP2A has been seen involved in orofacial development in mice; it is located in the NSCLP candidate region 6p24; it codes for a transcription factor which regulates expression of IRF6, a gene implied in NSCLP; finally, it is embroiled in the branchiooculofacial syndrome, that includes clefting as feature. A family based association analysis was performed with a sample study of 405 NSCLP triads. Evidence of association was obtained with both single marker and haplotype analyses, thus providing a support for TFAP2A in NSCLP aetiology.

Respiratory distress in Pierre Robin sequence: an experience with mandible traction by wires.

Congenital retrognathia and glossoptosis characterize isolated Pierre Robin sequence (iPRS); the small mandible and its retracted position cause retrodisplacement of the tongue and reduction of the oropharyngeal airway. These neonates may be affected by airway obstruction, feeding difficulties, failure to thrive, and chronic hypoxaemia. To solve the respiratory problems secondary to glossoptosis, various treatments have been described including prone positioning, a nasopharyngeal tube, glossopexy, and mandibular distraction. Over the last 28 years, the authors have treated 118 neonates and infants affected by iPRS by carrying out traction of the mandible using two parasymphyseal wires, positioned under local anaesthesia. All the procedures were successful, with no major complication. The patients' respiratory problems and apnoea disappeared suddenly after beginning traction.

Study of the PVRL1 gene in Italian nonsyndromic cleft lip patients with or without cleft palate.

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a complex genetic trait and little is known about its aetiology. Recent investigations on rare clefting syndromes provided interesting clues about genes involved in face development. The PVRL1 gene encodes nectin1, a cell-to-cell adhesion molecule. Mutations in its sequence have been shown to cause the rare autosomal recessive syndrome CL/P-ectodermal dysplasia syndrome (CLPED1), while heterozygosity for the mutation W185X seemed to increase the risk of non syndromic CL/P in a population from northern Venezuela. In the present study, we screened 143 Italian CL/P patients for mutations in PVRL1. Three rare sequence variants in exon 3 that create amino-acid changes were detected in a total of 7 patients. Two of these mutations were not found in a panel of 292 unaffected controls, while the third was found in two controls. This study describes new mutations that may represent genetic risk factors for CL/P. Even though a study to look at the effects of the mutations on nectin1 function was not feasible, supporting evidence was reported, thus confirming the involvement of PVRL1 in the aetiology of non-syndromic CL/P malformation.

Intracranial dislocation of the mandibular condyle: report of two cases and review of the literature.

Fractures of the mandibular condylar process are common and account for up to 40% of all mandibular fractures. Penetration of the condylar head into the middle cranial fossa is, however, rare. We have found reports of only 43 cases since 1834. The diagnosis of intracranial condylar dislocation is difficult, there are usually no particular symptoms or neurological signs. As a result, detailed radiological studies are necessary. In the absence of clear radiographic images of the condylar structures, computed tomography (CT) is essential to locate the fragments and to investigate and monitor intracranial lesions. This paper describes the diagnostic and surgical procedures used in two cases of condylar dislocation and discusses them with reference to previous cases. The use of a titanium screw, which was positioned intracranially in the first case, has not, to our knowledge, been described previously.

Linkage analysis of three candidate regions of chromosome 1 in nonsyndromic familial orofacial cleft.

Linkage analysis and mouse model knockout studies indicate that loci/genes mapping in different chromosome 1 regions are good candidates for nonsyndromic orofacial cleft (OFC) malformation. On this basis, three different regions of the chromosome 1 have been analysed, by linkage analysis, in 38 families with nonsyndromic OFC. Positive scores were obtained by pairwise analysis and a non-parametric linkage approach for the 1p36 region, with markers close to the MTHFR locus. Additional results allowed us to exclude the presence of an OFC susceptibility gene in the 1q21 and 1q32-42.3 regions.

CD44 standard form (CD44H) expression and distribution in dysfunctional human temporomandibular joint discs.

The expression pattern of the cell adhesion molecule CD44 standard form (CD44H) in dysfunctional human temporomandibular joint (TMJ) discs was studied immunohistochemically and compared with normal disc pattern in order to evaluate the expression of this adhesion molecule and correlate it to histopathological changes. Immunohistochemistry with anti-CD44H antibodies was performed on paraffin sections of pathological and normal discs. In normal TMJ discs, a moderate immunolabelling with anti-CD44H antibodies was detectable in fibroblastlike cells, in the few fibrochondrocytes and in chondrocytelike cells. In dysfunctional discs, the staining pattern and intensity varied according to the histopathological findings of the specimens. The TMJ discs showing abnormal collagen arrangement or fragmentation of collagen fibres presented overall the same immunolabelling pattern of normal discs. In the discs showing areas of fibrocartilaginous metaplasia, CD44H expression was upregulated in fibrochondrocytes and fibroblastlike cells, especially around the chondroid tissue. Overall, these results suggest that CD44H mediates the binding of some ECM proteins in TMJ disc cells. The up-regulation of CD44H observed in some dysfunctional TMJ discs seems to indicate a prevention of apoptosis in fibroblastlike cells and an important role in phenotypical change of fibrochondrocytes into chondroblastlike cells, enabling the aggregation of chondroid tissue pericellular matrix components.

Cellular S-100 protein immunostaining in human dysfunctional temporomandibular joint discs.

S-100 protein was detected immunohistochemically in diseased human temporomandibular joint discs with different degrees of pathology, and the findings compared with those of normal discs. In normal discs, large nerve trunks in the posterior ligament were strongly stained by anti-S-100 antiserum; the very few chondrocyte-like cells sometimes showed faint staining, while no staining was observed in any fibrochondrocyte-like or fibroblast-like cell. In dysfunctional discs, S-100 protein immunostaining seemed to correlate with structural pathological findings. The discs showing an abnormal collagen arrangement or fragmentation of collagen fibres presented overall the same immunolabelling pattern as normal discs. In discs with fibrocartilaginous metaplasia and dystrophic cartilage formation, fibrochondrocyte cells showed a very strong immunoreaction for S-100 protein and fibroblast-like cells in some instances were also positive. These findings suggest that S-100 upregulation in disc cells can be considered an attempt at tissue repair by chondroid metaplasia following an injury in that it enables fibroblast-like cells and fibrochondrocytes to acquire a chondrogenic phenotype.

Immunolocalization of gelatinase-A (matrix metalloproteinase-2) in damaged human temporomandibular joint discs.

The fibrous tissue of the articular disc of the dysfunctional temporomandibular joint undergoes deep and variable structural modifications. Here the concurrence of morphological changes and the expression of matrix metalloproteinase-2 (MMP-2) in damaged discs from individuals suffering joint dysfunction was investigated. Microscopic, ultrastructural and immunocytochemical investigations were made on variously damaged articular discs and on one control sample. Disaggregation of collagen fibres, an increase in cellular components and calcification of large areas of tissue were observed in the damaged discs. These modifications were accompanied by a positive immunoreaction pattern for MMP-2. Fibroblast-, chondroblast- and osteoblast-like cells displayed a positive cytoplasmic reaction. In samples displaying evidence of synovial hyperplasia, some cells of the synovial protrusions were MMP-2 immunoreactive. No MMP-2 staining was observed in the control sample. These findings demonstrate that structural modifications of the articular disc could be specific responses to changes in the function of the temporomandibular joint. Variations in extrinsic stimuli may activate intrinsic factors, such as MMPs, that induce structural modifications in the discal tissue.

Suggestive linkage between markers on chromosome 19q13.2 and nonsyndromic orofacial cleft malformation.

Nonsyndromic cleft lip with or without cleft palate (OFC) is a common birth defect that has genetic bases. The nature of the genetic contribution is still to be clarified; however, some chromosome regions and candidate genes have been proposed for this malformation. We examined linkage between BCL3, a proto-oncogene located in 19q13.2, and OFC in a sample composed of 40 multiplex pedigrees using both nonparametric and parametric methods. The affected pedigree member statistics and the transmission disequilibrium test supported a role for BCL3 in causing OFC, while no evidence of linkage or genetic heterogeneity was found with the lod score method.

Synovia hyperplasia and calcification in the human TMJ disk: a clinical, surgical, and histologic study.

The aim of the study was to investigate the morphologic modifications occurring in the synovial tissue after severe derangement of the articular structures with dislocation or perforation of the disks. Light microscopic, ultrastructural, and immunocytochemical investigations were performed on 10 disks. Arthroscopic examinations had documented adhesions between the diskal surfaces and the glenoid eminence or the condylar head in all the selected cases. Histologic examination showed a remarkable hyperplasia of the synovial tissue with the formation of prominent protrusions. An evident increase of type B (fibroblast-like) cells and the presence of cells with the ultrastructural and immunocytochemical characteristics of myofibroblasts were observed. Foci of mineral precipitates and large deposits of calcified tissue were present in the synovial villi in three samples. Our observations suggest that functional failure and morphologic lesions of the synovia may be caused by arthropathy.

Endoarticular loose bodies and calcifications of the disk of the temporomandibular joint: morphological features and chemical composition.

We studied articular disks and endoarticular loose bodies taken from patients suffering from different types of temporomandibular joint (TMJ) pathology. The scanning electron microscopy (SEM) analysis of the disks and the endoarticular loose bodies was followed by a chemical-compositional analysis using an energy dispersive spectrometer (EDS) and by characterization of the crystalline phases by X-ray powder diffraction (XRD). The articular disks were composed of a central radiopaque area lacking any evident structural features, surrounded by compact bundles of collagen fibers. EDS and XRD analyses showed that endodiscal radio-opaque areas were hydroxyapatite. By SEM, we observed a fibrous network only in circumscribed areas of the endoarticular loose bodies. The chemical-compositional analysis showed that the loose bodies were composed of calcite (CaCO3). The results of this investigation, along with the clinical history of the patients, allow us to formulate some hypotheses regarding the etiopathogenesis of these structural anomalies. The endodiscal calcifications could be the result of a chronic inflammatory process that produces displastic alterations of the articular disk. Moreover, an acute inflammatory process with modifications in the mechanisms of the synovial fluid turnover seems to be the event that leads to the formation of endoarticular loose bodies.

Collagen fiber arrangement in temporo-mandibular joint (TMJ) disks from human subjects with functional diseases. Scanning electron microscopy investigations.

Twelve articular disks from patients with temporo-mandibular joint (TMJ) arthropathy were studied and compared with two normal disks. Scanning electron microscopy (SEM) examination of the surfaces and of longitudinal and cross-sections of the disks allowed the observation of the arrangement of the collagen fiber component in different parts of the disk. The superficial part of the articular disks appears to be formed by rather compact fibers. The internal portion is usually formed by bundles of collagen fibers in sheets, alternating with isolated fibers arranged in a parallel or irregular way. In some samples, blood vessels were observed. Our investigations suggested that the appearance of vascularization is the first remarkable histological change that can be observed in functionally abnormal articular disks.

[Dynamic magnetic resonance of the temporomandibular joint. Observations and findings]. / La risonanza magnetica dinamica dell'articolazione temporomandibolare. Osservazioni e rilievi.

Condylar movements can be executed only if the TMJ morphology can satisfy functional needs of the masticatory apparatus. Articular components have to be in good relation with dento-skeletal functional anatomy: if this does not occur, mandibular dynamics may establish some functional stresses on the condylar head and the articular eminence. These overloaded structures and particularly their functional surfaces react to this situation to be remodelling and deformation of the articular cavity. In our work we have used a new method to analyse condylar dynamics using MRI. The reconstruction of mandibular movements, using this instrumentation, permits to make some useful observations on the functional capability of TMJ to adjust itself to different maxillofacial morphologies and, consequently, how this joint can fall in a dysfunctional and pathological condition.

Frontoethmoidal meningoencephalocele. A one-stage correction, reconstruction, and plating by means of the micro system.

This case report on one stage surgical treatment of meningoencephalocele offers the opportunity for a revision of the most recent trends expressed by other authors on this topic. Surgical technique involved a system of rigid fixations by means of microplates which, according to our experience in other cases, is particularly advisable in pediatric age. We find that the simultaneous utilization of calvarial bone grafts facilitates a better reconstruction of the cranial base, and also offers greater stability in results.