Analysis of familial incidence of non-syndromic cleft lip and palate in a Brazilian population

Background: The purpose of this study is to follow the familial incidence of non-syndromic or isolated cleft lip, with or without cleft palate (NSCL/P), and to analyze the relationships between the type of NSCL/P in the affected individual and his/her parent, looking at children in the first grade. Material and Methods: To investigate the familial incidence of NSCL/P we analyzed the records of 185 patients from 2004-2008, retrospectively. Detailed histories were collected regarding the familial incidence of NSCL/P. For the 185 individuals, the relationship between the type of NSCL/P and the sociodemographic and personal characteristics of the affected person and her/his cleft relatives was obtained. Results: The individuals were 42 carriers of CL, 109 with CLP (joined in one group) and 34 with CP (p<0.001). Of the total of participants, 65 (35.13%) presented a positive history of cleft in their families and 120 (64.86%) presented a negative history (p<0.001). There were differences between the cleft groups according to types of cleft and positive familial history (p<0.001). In both groups, the relatives with higher incidence of NSCL/P were cousins, with the same pattern of distribution between the two groups (p=0.175). Conclusions: Most frequently, fissures result from CL/CLP with no familial history. However, CL/CLP was found in familial cases and cousins were the relative type more likely to be affected

Prognostic value of immunoexpression of CCR4, CCR5, CCR7 and CXCR4 in squamous cell carcinoma of tongue and floor of the mouth

Diverse studies have evidenced that chemokines can play a critical role in pathogenesis of oral squamous cell carcinoma (SCC). The main chemokines involved in oral carcinogenesis, tumor invasion and metastasis are CCR4, CCR5, CCR7 and CXCR4, and our aim was to evaluate the prognostic value of the immunoexpression of these chemokines in SCC of tongue and floor of the mouth. A retrospective descriptive study of the immunohistochemical expression of CCR4, CCR5, CCR7 and CXCR4 in paraffin-embedded samples of 124 patients with SCC of the tongue and floor of the mouth was performed, considering 98 cases from Brazil and 26 cases from Chile. Associations between variables were analyzed using chi-square test. Survival curves were performed using the Kaplan-Meier method and compared with long-rank test. For multivariate survival analysis, the Cox hazard model was established. The level of significance established was p?0.05. The statistical analysis showed that samples with well or moderate WHO model differentiation (p=0.001) and a high expression of CCR5 (p=0.05) were significantly associated with a higher disease specific survival, which were also observed in Cox´s multivariate analysis (p=0.01). A higher expression of CCR7 (p=0.01) interfered significantly in disease-free survival in univariate analysis and in Cox´s multivariate analysis (p=0.05). These results support additional evidence, showing that chemokine receptors CCR5 and CCR7 are helpful as biomarkers of poor prognosis in patients with SCC of the tongue and floor of the mouth

Waardenburg syndrome type I: dental phenotypes and genetic analysis of an extended family

Background: The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods: To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results: The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions: These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS

Two rare cases of oral metastasis arising from lung adenocarcinoma and esophageal carcinoma

Metastasis to the oral cavity are rare, representing only 1% of all oral malignancies, and originate from various sites such as the breast, prostate, lung and kidney. Clinically, they can simulate reactive and inflammatory lesions common in the oral cavity, and the clinical and microscopic diagnosis of these metastasis is a challenge. In this article, we report two new cases of esophageal and lung metastasis to oral tissues, highlighting their clinical characteristics and the process of diagnostic elucidation. We emphasize the importance for clinicians to consider the possibility of metastatic lesions in the oral cavity in patients previously diagnosed with malignant lesions in distant tissues and organs

Contribution of polymorphisms in genes associated with craniofacial development to the risk of nonsyndromic cleft lip and/or palate in the Brazilian population

Background and Objective: Nonsyndromic cleft lip and/or palate (NSCL/P) is a complex disease associated with both genetic and environmental factors. One strategy for identifying of possible NSCL/P genetic causes is to evaluate polymorphic variants in genes involved in the craniofacial development. Design: We carried out a case-control analysis of 13 single nucleotide polymorphisms in 9 genes related to craniofacial development, including TBX1, PVRL1, MID1, RUNX2, TP63, TGFB3, MSX1, MYH9 and JAG2 , in 367 patients with NSCL/P and 413 unaffected controls from Brazil to determine their association with NSCL/P. Results: Four out of 13 polymorphisms (rs28649236 and rs4819522 of TBX1, rs7940667 of PVRL1 and rs1057744 of JAG2 ) were presented in our population. Comparisons of allele and genotype frequencies revealed that the G variant allele and the AG/GG genotypes of TBX1 rs28649236 occurred in a frequency significantly higher in controls than in the NSCL/P group (OR: 0.41; 95% CI: 0.25-0.67; p=0.0002). The frequencies of rs4819522, rs7940667 and rs1057744 minor alleles and genotypes were similar between control and NSCL/P group, without significant differences. No significant associations among cleft types and polymorphisms were observed. Conclusion: The study suggests for the first time evidences to an association of the G allele of TBX1 rs28649236 polymorphism and NSCL/P

Immunoexpression of alfa2-integrin and Hsp47 in hereditary gingival fibromatosis and gingival fibromatosis-associated dental abnormalities

Objective: The purpose of the present study was to investigate the expression of the ?2-integrin subunit and heat shock protein 47 (Hsp47) in two families with isolated gingival fibromatosis (GF) form and one family with GF associated with dental abnormalities and normal gingiva (NG). Study Design: Immunohistochemistry was performed with antibodies against ?2-integrin and Hsp47 in specimens from two unrelated families with hereditary gingival fibromatosis (Families 1 and 2) and from one family with a gingival fibromatosis-associated dental abnormality (Family 3); NG samples were used for comparison. The results were analysed statistically. Results: Immunoreactivity for ?2-integrin and Hsp47 was observed in the nucleus of epithelial cells of both the basal and suprabasal layer and a more discreet signal was noted in connective tissue in all study samples. Hsp47 showed higher immunoreactivity in Family 2 compared with the other families (p?0.05). Despite the markup ?2-integrin was higher in Family 3 there was no statistically significant difference between the families studied (p?0.05). Conclusions: Our results confirmed the heterogeneity of GF, such that similar patterns of expression of the condition may show differences in the expression of proteins such as Hsp47. Although no difference in ?2-integrin expression was observed between GF and NG groups, future studies are necessary to determine the exact role of this protein in the various forms of GF and whether it contributes to GF pathogenesis