Search

Abstract Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations. Objective This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population. Methodology A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored. Results WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04–1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058. Conclusion The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population.

A systematic review (SR) requires several steps to be conducted. A major and initial challenge is to formulate a focused research question that may have high scientific relevance to provide evidence-based results and strategies. This narrative mini-review aims to present different categories of systematic reviews currently applied in Head and Neck Cancers (HNC), focusing on the strategies to provide results for evidence-based decision making. The SRs identified were of intervention, diagnostic testing, prognosis, in vitro and in vivo studies, prevalence, and epidemiological studies, and of association and risk factors. Focused questions that define the type of review, whether it is a therapy question (intervention), a question of prevalence or an outcome (prognosis) of disease, are discussed. Additionally, the importance in building interesting research questions and following all proposed steps to produce quality evidence are highlighted. This narrative mini-review may guide future research by showing how to perform and report relevant evidence in terms of HNC.

COVID-19, a respiratory illness with a global impact on millions, has recently been linked to manifestations affecting various bodily systems, including the oral cavity. Studies highlight oral issues, like ulcers, blisters, and white patches, alongside olfactory and gustatory dysfunction, influencing an individual’s quality of life. In this context, our study aimed to assess the frequency of oral lesions, olfactory and gustatory disorders, and xerostomia resulting from COVID-19. An observational study was conducted with 414 patients to evaluate the frequency of oral symptoms resulting from COVID-19. Patients were diagnosed with mild symptoms and evaluated through clinical examination of the oral cavity and a questionnaire to assess functional alterations. The findings showed that 139 out of 414 patients presented clinical manifestations, with oral lesions being the most prevalent (19.1%), followed by gustatory disorders (18.1%), xerostomia (14.2%), and olfactory dysfunction (14%). The most prevalent oral lesions were ulcerations (n = 51), candidiasis (n = 8), and erythema or red plaques (n = 7). Unfortunately, 50 (12.1%) patients died during this study. Therefore, oral lesions, olfactory and gustatory dysfunctions, and xerostomia are common symptoms associated with COVID-19.

The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the PRISMA 2020 checklist guidelines, and the search was conducted using PubMed, Scopus, Lilacs, Web of science, Livivo, and EMBASE and supplemented by a gray literature search on Google Scholar and ProQuest, applying key terms relevant to the research questions. The systematic review identified 47 types of syndromes in 83 studies, and the most common was hypohidrotic ectodermal dysplasia, which was reported in 24 patients in 22 studies. Other common syndromes that reported oligodontia included Axenfeld–Rieger syndrome, Witkop’s syndrome, Ellis–van Creveld syndrome, blepharocheilodontic syndrome, and oculofaciocardiodental syndrome. The X-linked mode of inheritance was the most reported (n = 13 studies), followed by the autosomal dominant (n = 13 studies). The review describes the main syndromes that may have oligodontia as a clinical sign and reinforces the need for orodental–facial examining for adequate diagnosis and treatment of the affected patients. Molecular analysis in order to better understand the occurrence of oligodontia is imperative.

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior, long-term survival is poor due to locoregional recurrence in approximately 40% and distant metastasis in up to 60% of patients who undergo radical treatment. The histological parameters of ACC and the combination of these parameters in histopathological grading systems provide valuable prognostic information about the clinical course of the disease. Within this context, this review aims to analyze the impact of histopathological parameters, individual or combined in histopathological grading systems of malignancy, on ACC prognosis. Individual histopathological parameters such as solid pattern, presence of tumor necrosis, high-grade transformation, dominance of the epithelial component, presence of perineural and lymphovascular invasion, and positive surgical margins have negative impacts on the survival of patients with ACC. There are currently four histopathological grading systems for ACC; however, few studies have validated these systems and most of them explored small cohorts with short follow-up. Considering that the application of grading systems has been associated with ACC prognosis, a broader validation will allow not only their use for prognostic prediction but also assist in treatment planning.

Associations of CRISPLD2 (cysteine-rich secretory protein LCCL domain containing 2) and genes belonging to its activation pathway, including FOS (Fos proto-oncogene), CASP8 (caspase 8) and MMP2 (matrix metalloproteinase 2), with nonsyndromic orofacial cleft risk, have been reported, but the results are yet unclear. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) in FOS, CASP8 and MMP2 and to determine their SNP-SNP interactions with CRISPLD2 variants in the risk of nonsyndromic cleft lip with or without cleft palate (NSCL±P) in the Brazilian population. The SNPs rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) were genotyped using TaqMan allelic discrimination assays in a case-control sample containing 801 NSCL±P patients (233 nonsyndromic cleft lip only (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)) and 881 healthy controls via logistic regression analysis adjusted for the effects of sex and genomic ancestry proportions with a multiple comparison p value set at ≤0.01. SNP-SNP interactions with rs1546124, rs8061351, rs2326398 and rs4783099 in CRISPLD2 were performed with the model-based multifactor dimensionality reduction test complemented with a 1000 permutation-based strategy. Although the association between FOS rs1046117 and risk of NSCL±P reached only nominal p values, NSCLO risk was significantly higher in carriers of the FOS rs1046117 C allele (OR: 1.28, 95% CI: 1.10–1.64, p = 0.004), TC heterozygous genotype (OR: 1.59, 95% CI: 1.16–2.18, p = 0.003), and in the dominant model (OR: 1.50, 95% CI: 1.10–2.02, p = 0.007). Individually, no significant associations between cleft risk and the SNPs in CASP8 and MMP2 were observed. SNP-SNP interactions involving CRISPLD2 variants and rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) yielded several significant p values, mostly driven by FOS rs1046117 and CASP8 rs3769825 in NSCL±P, FOS rs1046117 in NSCLO and CRISPLD2 rs8061351 in NSCLP. Our study is the first in the Brazilian population to reveal the association of FOS rs1046117 with NSCLO risk, and to support that CRISPLD2, CASP8, FOS and MMP2 interactions may be related to the pathogenesis of this common craniofacial malformation.

Aim: To characterize the patterns of dental anomalies (DA) in the mixed and permanent dentitions of patients with nonsyndromic oral cleft (NSOC). Methods: This cross-sectional, observational, case-control study included 173 patients, 61 with mixed dentition (NSOC=29 and control=32) and 112 with permanent dentition (NSOC=57 and control=55). All subjected were submitted to clinical and radiographic examination. Dental anomalies of eruption, number, size and shape outside the cleft area were considered. Results: Although there was no statistical significance among patients with mixed dentition, dental agenesis was the anomaly more common in this group. In patients with permanent dentition, a higher prevalence of DA in NSOC group compared to control group was observed (p=0.02). Gyroversion and dental agenesis were the DA more frequently observed in the permanent dentition and the second premolar was the tooth more affected (p=0.003). Mandible and the left side were more involved, and dental agenesis was more frequently found in patients with unilateral cleft lip with or without cleft palate (NSCL±P). Conclusion: Our findings show a higher frequency of DA in NSOCs than in the control group in patients with permanent dentition, mainly due to a higher occurrence of agenesis of second premolars in patients with unilateral NSCL±P.

In late December 2019, a cluster of unexplained pneumonia cases was diagnosed in Wuhan, China, and few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the relevant infected disease has been named as coronavirus disease 2019 (COVID-19) by the World Health Organization respectively. The COVID-19 epidemic is spreading in China and all over the world now...

Aim: : To describe the clinical, demographic and environmental features associated with NSCL/P (nonsyndromic cleft lip and/or palate) patients born in western Parana state, Brazil. Methods: This cross-sectional, observational, retrospective study included 188 patients attended at the Association of Carriers of Cleft Lip and Palate - APOFILAB, Cascavel-Parana, between 2012 and 2014. Information on demographic characteristics, medical and dental histories and life style factors were obtained from records and personal interviews. Results: Among the 188 patients, cleft lip and palate (CLP) was the most frequent subtype (55.8%), followed by cleft lip only (CLO, 25.0%) and cleft palate only (CPO, 19.2%). Caucasian males were the most affected, although no differences among types of cleft were observed. The otorhinolaryngologic and respiratory alterations were the most frequent systemic alterations in NSCL/P patients, and more than 80% of the NSCL/P mothers reported no vitamin supplements during the first trimester of pregnancy. Conclusions: This study revealed that the prevalence of nonsyndromic oral cleft types in this cohort was quite similar to previously reported prevalence rates. Systemic alterations were identified among 23.4% of the patients and patients with CLP were the most affected. History of maternal exposition to environmental factors related to nonsyndromic oral clefts was frequent and most mothers reported no vitamin supplements during the pregnancy. This study highlights the importance of identifying systemic alterations and risk factors associated with NSCL/P in the Brazilian population for planning comprehensive strategies and integrated actions for the development of preventive programs and treatment.

The X-linked hypophosphatemic rickets (XLHR) is the most common type of rickets in developed countries, with an incidence of 1- 20.000 individuals. It results from a defect in renal tubular phosphate transport, which leads to a hypophosphatemia. This alteration is responsible for abnormalities of bones and decreased dental mineralization. One of the most important buccal alteration is periapical and/or periodontal abscess without caries or trauma. We reported one case of XLHR that sought our department for dental treatment. The patient presented generalized periodontal disease and radiolucent images at the periapical regions of lateral superior incisors and first and second superior molars. Periodontal and endodontic treatments were performed, being the last one with successive curative changes of calcium hydroxide and filling with molded gutta-percha cones. The patient is in follow-up being examined routinely without presenting alterations.

Dear Editor, In 2020, when we searched the word "Coronavirus" in PubMed, 19,085 papers were found, a daily average of 100.9 papers/day. These papers discussed several aspects of COVID-19 pandemic, including signals and symptoms, spread of virus, risk of health workers, drugs and treatment (https://www.ncbi.nlm.nih.gov/pubmed/). The scientific literature related to dentistry is still limited, with studies exploring areas of clinical care [1-5], immunobiology of oral mucosa [6], and the use of social media and telemedicine [7]. However, no reports on impact of treatment and management of patients with oral clefts have yet been described. Nonsyndromic oral clefts (NOC) are amongst the most prevalent congenital abnormalities in humans (approximately 1 in 700 live births), and are considered important public health problem mainly due to the high risk of mortality, reaching up to 30% in underdeveloped countries and in specific areas in developed countries, and significant morbidities [8]. Both esthetic consequences and functional impairment, such as restriction of maxillofacial growth, dental changes, speech and chewing disorders and hearing problems, affect patients’ health and quality of life and demand longstanding treatment, in some cases for the entire life of patient [9].

Abstract Background Aim of the study was to evaluate the gelatinolytic activity in the saliva and gingival crevicular fluid from a sample group of subjects with Marfan syndrome. Methods Two groups were analyzed in this case-control study. A group of 28 subjects with Marfan syndrome (MG) was recruited from the Centre for Rare Disease, Marfan Clinic of Tor Vergata University Hospital. The second sample, 23 subjects, with the same characteristics and without any syndrome, was the control group (CG). Saliva and gingival crevicular fluid were collected and transferred to a sterile test tube and stored frozen at − 20 °C until analysis at the Medical Chemistry Laboratory. Gelatin substrate zymography was used for the evaluation and characterization of saliva and crevicular fluid proteinases. Correlation test and Student’s t-test have been used to analyze data. Results In all samples different gelatin-degrading activities were observed. Two bands, which are related to the molecular weights of pro-MMP-9 and active MMP-9, respectively, were detectable in 100% of Marfan and control samples. MMP-2 activity was higher in Marfan group. Additional bands (55/48 kDa), corresponding to the activated forms of collagenase (MMP-13), were observed in saliva samples of both groups. Conclusions The association of an enhanced activity by MMP-13 with an increased amount of active MMP-9 might be an important biomarker for the diagnosis of Marfan syndrome.

Abstract: Kawasaki disease (KD) is a vasculitis with predilection for coronary arteries. Due to a lack of reliable confirmatory laboratory tests, the diagnosis of KD is based on a characteristic pattern of clinical findings that appear in a typical temporal sequence. The diagnostic criteria have been periodically modified and the American Heart Association has proposed the most recent guidelines for its diagnosis. However, patients may have incomplete or atypical forms of KD and diagnosis can often be difficult. Because oropharyngeal manifestations are a common and important feature for diagnosing KD and recent studies have hypothesized a possible association between KD and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this review we highlight the importance of dentists in the diagnosis of KD and its potential association with SARS-CoV-2.

Multiple studies have demonstrated an association between cancer and nonsyndromic oral clefts in different populations. In this study, we assessed the occurrence of nonsyndromic oral clefts in families of patients with acute lymphoblastic leukemia (ALL, n = 50) and controls (n = 125). The parents of the patients answered a questionnaire with basic demographic information and family history of nonsyndromic oral clefts in first-degree relatives. Statistical analysis was carried out using Fisher’s exact test. In the ALL group, 22 (44%) were male and 28 (56%) were female, and the average age was 13.2 ± 12.2 years. In the control group, 64 (51.2%) were male and 65 were female and the average age was 11.3 ± 10.3 years. Two out of 50 patients (4%) with acute lymphoblastic leukemia had a positive history of nonsyndromic oral clefts, whereas there were no reported occurrences of nonsyndromic oral clefts in the control group (OR: 12.94, 95% CI: 0.61−274.6, p = 0.08). Despite the limited population, the frequency of nonsyndromic oral clefts was increased in the first-degree relatives of patients with acute lymphoblastic leukemia. Studies with larger samples and molecular analyses are needed to better understand the possible etiological relationship between cancer and nonsyndromic oral clefts.

Objective: To discuss the risk of cancer among relatives of individuals with cleft lip and palate (CL/P), as well as the risk of CL/P among relatives of individuals with cancer, since studies published currently have suggested an increased risk of cancer among relatives of cleft individuals. Design: A systematic literature review was carried out in accordance with the Cochrane Collaboration Group protocol, including literature search strategy, selection of papers through the inclusion and exclusion criteria, data extraction and quality assessment. PubMed, Scopus and ISI - Web of Science databases were systematically searched using the fallowing search strings: “cleft lip and palate” AND “cancer”, “oral clefts” AND “cancer” and “orofacial clefts” AND “cancer”. Results: From 653 studies accessed, 8 comprised the final sample: 6 investigating CL/P index cases and their family history of cancer and 2 investigating individuals with cancer and their family history for CL/P. The sample sizes were not homogeneous. Oral clefts, the type of cancer and the degree of kinship family were not categorized in all studies. Leukemia, breast cancer and colon cancer were the most cited types, even as first-and-second degree relatives. Conclusions: An increased risk of cancer among relatives of cleft individuals could not be entirely confirmed. However, studies with this specific purpose suggest that first-and-second degrees relatives of cleft individuals have some types of cancer more often than unexposed families, highlighting that future studies should expand their samples to investigate possible common molecular mechanisms that allow relating oral clefts and cancer.

The aim of this study was to determine the frequency of leukemia in parents of patients with nonsyndromic cleft lip and/or cleft palate (NSCL/P). This case-control study evaluated first-degree family members of 358 patients with NSCL/P and 1,432 subjects without craniofacial alterations or syndromes. Statistical analysis was carried out using Fisher’s test. From the 358 subjects with NSCL/P, 3 first-degree parents had history of leukemia, while 2 out of 1,432 subjects from the unaffected group had a family history of leukemia. The frequency of positive family history of leukemia was not significantly increased in first-degree relatives of patients with NSCL/P.

OBJECTIVES: Goldenhar syndrome (GS) is a relatively common developmental disorder characterized by craniofacial anomalies in association with vertebral, cardiac, renal, and central nervous system defects. This paper describes GS features with special emphasis on oral characteristics. MATERIAL AND METHODS: The clinical features of 6 patients with GS aged 3 months to 12 years are described, and a brief review of the literature about this genetic disorder is presented. RESULTS: All patients demonstrated the classical triad of GS, including mandibular hypoplasia resulting in facial asymmetry, ear and/or eye malformation, and vertebral anomalies. In addition, renal and gastrointestinal abnormalities were observed in 2 patients. Regarding the oral involvement, 2 patients presented cleft lip and palate, and 1 patient had temporomandibular joint malformation. Malocclusion was found in all patients. CONCLUSION: Our orofacial findings correlate with the reported cases in the literature, and point out that after diagnosis GS patients need to be examined for systemic abnormalities.

Cyclosporin A (CyA) induces gingival overgrowth via its stimulatory effects on expression of transforming growth factor-beta1 (TGF-β1) and collagen. It is not known whether CyA has a direct effect on gingival fibroblasts or induces its effect indirectly via stimulation of myofibroblast transdifferentiation. The present study was undertaken to examine the in vivo and in vitro effect of CyA on myofibroblast transdifferentiation. Rats were treated for 60 days with a daily subcutaneous injection of CyA, and the gingival overgrowth tissue was analyzed by immunohistochemistry. In vitro, fibroblasts from normal gingiva (NG) were cultured in the presence of different concentrations of CyA, and subjected to semi-quantitative reverse transcriptase-polymerase chain reaction and western blot. Although CyA treatment stimulated TGF-β1 expression by NG fibroblasts, it lacked to induce expression and production of isoform α of smooth muscle actin (α-SMA), the specific myofibroblast marker. The expression levels of connective tissue growth factor (CTGF), which has been considered a key molecule to promote the transdifferentiation of myofibroblasts via TGF-β1 activation, were unaffected by CyA. Our results demonstrate that CyA-induced gingival overgrowth is not associated with activation of myofibroblast transdifferentiation, since CyA is not capable to increase CTGF expression.

The aim of this work was to study the immunohistochemical expression of androgen receptor, estrogen receptor and progesterone receptor in pleomorphic adenomas, Warthin's tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas of salivary glands. A total of 41 pleomorphic adenomas, 30 Warthin's tumors, 30 mucoepidermoid carcinomas and 30 adenoid cystic carcinomas were analyzed, and the immunohistochemical expression of these hormone receptors were assessed. It was observed that all cases were negative for estrogen and progesterone receptors. Androgen receptor was positive in 2 cases each of pleomorphic adenoma, mucoepidermoid carcinoma and adenoid cystic carcinoma. In conclusion, the results do not support a role of estrogen and progesterone in the tumorigenesis of pleomorphic adenomas, Warthin's tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas. However, androgen receptors can play a role in a small set of salivary gland tumors, and this would deserve further studies.

The aim of the present study was to analyze the prevalence of nonsyndromic oral clefts in children receiving treatment at the Center for the Rehabilitation of Craniofacial Anomalies, José do Rosário Vellano University, Alfenas, MG, Brazil. All the data for the epidemiological study was retrieved from the files of 126 pediatric patients with oral clefts without any additional malformation, who came to the center for treatment between 2000 and 2005. A predominance of clefts was observed in Caucasians, and the ratio of male to female was 1.3. Males were 2.57 times more affected by cleft lip and palate (CLP) than females. CLP with a prevalence of 39.68% and isolated cleft lip (CL) with a prevalence of 38.09% were the most common anomalies, followed by isolated cleft palate (CP; 22.23%). Complete and unilateral CLP (26.19%) presented the highest prevalence, followed by incomplete and unilateral CL (23.81%). The present study presents the experience of a reference hospital in the state of Minas Gerais; however, the real prevalence of oral clefts in Brazil is still unknown. Our findings differ from those of a few previous Brazilian reports because they suggest similar prevalences of CLP and CL, and a higher prevalence of CLP in Caucasian males.O objetivo do presente estudo foi analisar a prevalência de fissuras orais não-sindrômicas em crianças que receberam tratamento no Centro de Reabilitação de Anomalias Craniofaciais da Universidade José do Rosário Vellano, Alfenas, MG, Brasil. Todos os dados epidemiológicos deste estudo foram obtidos dos arquivos de 126 pacientes pediátricos com fissuras orais sem outra malformação adicional que compareceram ao Centro para tratamento entre 2000 e 2005. O predomínio das fissuras foi observado em caucasianos e a relação entre homens e mulheres foi de 1,3. Os homens foram 2,57 vezes mais atingidos por fissuras lábio-palatais (FLP) do que as mulheres. FLP com prevalência de 39,68% e fissuras labial isolada (FL) com prevalência de 38,09% foram as anomalias mais comuns, seguidas por fissuras palatinas isoladas (FP, 22,23%). As FLP completas e unilaterais (26,19%) foram as de maior prevalência, seguidas por FL incompletas e unilaterais (23,81%). O presente estudo mostrou a experiência de um Hospital de Referência em Minas Gerais; contudo, a verdadeira prevalência de fendas orais ainda é desconhecida. Nossos achados divergem dos de alguns poucos estudos anteriores por demonstrar prevalências similares de FLP e FL, e um acometimento maior de FLP em caucasianos do sexo masculino.

Tooth germ development is associated with morphological and biochemical changes of the dental papilla and enamel organ. Enzymes with gelatinolytic activities were studied by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzymography in tooth germ of newborn to 15-day-old rats. Three major bands with gelatinolytic activity were detected at all periods and characterized as the latent and active forms of MMP-2 using their molecular weight and activity dependent on Zn++ and Ca++ ions as criteria. Expression and activity of MMP-2 increased progressively from 0 to 15 days after birth. Mechanical separation of the tooth germ from 10-day-old rats showed that the gelatinolytic activity was localized mainly in the dental papilla and not the dental organ. These data indicate that the expression and activity of MMP-2 varies during the development and maturation of rat first molar tooth germ.

Clinical manifestations of tuberous sclerosis (TS) are variable, and oral involvement occurs in less than 10% of the affected patients. We reported herein a nine-year-old boy with dental enamel pits and gingival nodular lesions, histologically diagnosed as angiofibromas that leaded to the diagnosis of a family with TS. In this report, we demonstrated the multiprofessional importance in the diagnosis of TS. Early diagnosis of TS is essential for an appropriate treatment of the affected patients and genetic counseling.