RESUMO
BACKGROUND: Hereditary gingival fibromatosis (HGF) is an uncommon genetic condition characterized by slow but progressive fibrous, non-hemorrhagic, and painless growth of the gingival tissues due to the increased deposition of collagen and other macromolecules of the extracellular matrix. HGF occurs in approximately 1:750,000 individuals and can exhibit dominant or recessive inheritance. To date, five loci (2p21-p22, 2p22.3-p23.3, 4q12, 5q13-q22, and 11p15) and three genes [REST (RE1-silencing transcription factor), SOS1 (Son-of-Sevenless-1), and ZNF862 (zinc finger protein 862 gene)] have been associated with HGF. Here, our study aimed to identify genetic variants associated with HGF by applying whole-exome sequencing (WES) and bioinformatics analyses. METHODS: Thirteen Brazilian individuals with HGF and nine relatives without HGF from four unrelated families were chosen for our investigation. Blood collected from the patients and their relatives were used for WES. Five Web-available tools, namely, CADD, PolyPhen, SIFT, Mutation Taster, and Franklin's algorithms, were used to predict protein damage. RESULTS: WES revealed pathogenic variants affecting the known HGF genes REST (c.1491_1492delAG) and SOS1 (c.3265_3266insTAAC) in two families. Additionally, potentially pathogenic variants segregating in the other two families were mapped to ALK receptor tyrosine kinase gene (ALK) (c.361C > T) and to collagen type I receptor and thrombospondin receptor gene (CD36) (c.1133G > T). CONCLUSION: Our findings reinforce the high genetic heterogeneity of HGF, identifying new variants in HGF known genes (REST and SOS1) and ALK and CD36 as new genes that cause HGF.
Assuntos
Fibromatose Gengival , Heterogeneidade Genética , Humanos , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Antígenos CD36/genética , Linhagem , Receptores Proteína Tirosina Quinases/genéticaRESUMO
Hereditary gingival fibromatosis (HGF) is a rare genetic condition characterized by slow and progressive gingival enlargement. The gingival overgrowth often delays teeth eruption and may cause serious functional and aesthetic problems. We reported a case of a 10-year-old female child presenting a generalized gingival enlargement covering almost all the maxillary and mandibular teeth and resulted in problems for swallowing, speaking, and poor aesthetics. An incisional biopsy was performed and revealed a hypocellular and hypovascular dense collagenous tissue covered by squamous epithelium exhibiting acanthosis and elongated rete ridges. The diagnosis was HGF. The treatment instituted was an association of gingivectomy with a rigorous program of oral hygiene and follow-up. Herein, we describe a rare non-syndromic case of generalized HGF, including clinical and microscopical features, as well as highlighting the importance of correct diagnosis of this genetic condition.
Assuntos
Humanos , Feminino , Criança , Fibromatose Gengival/patologia , Dentição Permanente , GengivectomiaRESUMO
Objective: To compare the rate of cell proliferation and expression of antiapoptotic protein Bcl-2 between drug-induced gingival overgrowth (DIGO) and clinical healthy gingiva (CHG) and to establish associations with histopathological features. Material and Methods: Twenty specimens of DIGO and 20 CHG specimens were submitted to morphological and immunohistochemical analysis by light microscopy. Cell proliferation (Ki-67) and the expression of Bcl-2 were evaluated in epithelial cells and spindle-shaped mononuclear cells of the connective tissue by establishing the labeling index (LI). Results: In epithelial tissue, the mean LI for Ki-67 was 17.2% in DIGO and 21.71% in CHG (p = 0.137). The mean LIs for Bcl-2 in epithelial tissue were 14.67% and 10.24% in DIGO and CHG, respectively (p = 0.026). In connective tissue, DIGO and CHG specimens exhibited low LIs for Ki-67 and Bcl-2, with mean values of less than 0.5% in both groups. No significant differences in the LIs for Ki-67 or Bcl-2 in epithelial tissue were observed according to the degree of collagenization, degree of vascularization and intensity of inflammatory infiltration (p > 0.05). No significant correlations were observed between the LIs for Ki-67 and Bcl-2 (p > 0.05). Conclusion: The present results suggest that the pathogenesis of DIGO does not involve increased proliferation or decreased apoptosis of fibroblasts. On the other hand, the morphological pattern of elongated epithelial cristae observed in DIGO could mainly be due to the inhibition of keratinocyte apoptosis and not to increased proliferation of these cells.
Assuntos
Proliferação de Células , Fibromatose Gengival/patologia , Genes bcl-2 , Imuno-Histoquímica/métodos , Antígeno Ki-67 , Brasil , Estatísticas não ParamétricasRESUMO
Since the 1940s, a proliferative gingival disease called hereditary hyperplastic gingivitis (HHG) has been described in the farmed silver fox, Vulpes vulpes (Dyrendahl and Henricson 1960). HHG displays an autosomal recessive transmission and has a pleiotropic relationship with superior fur quality in terms of length and thickness of guard hairs. An analogous human disease, hereditary gingival fibromatosis (HGF), is characterized by a predominantly autosomal dominant transmission and a complex etiology, occurring either as an isolated condition or as a part of a syndrome. Similar to HHG, the symptom most commonly associated with syndromic HGF is hypertrichosis. Here we explore potential mechanisms involved in HHG by comparison to known genetic information about hypertrichosis co-occurring with HGF, using an Affymetrix canine genome microarray platform, quantitative PCR, and candidate gene sequencing. We conclude that the mitogen-activated protein kinase pathway is involved in HHG, however despite involvement of the mitogen-activated protein kinase kinase 6 gene in congenital hypertrichosis with gingival fibromatosis in humans, this gene did not contain any fixed mutations in exons or exon-intron boundaries in HHG-affected foxes, suggesting that it is not causative of HHG in the farmed silver fox population. Differential up-regulation of MAP2K6 gene in HHG-affected foxes does implicate this gene in the HHG phenotype.
Assuntos
Fibromatose Gengival/genética , Raposas/genética , Doenças da Gengiva/genética , Hipertricose/genética , Animais , Cães , Fibromatose Gengival/patologia , Estudos de Associação Genética , Genoma , Genômica , Doenças da Gengiva/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipertricose/patologia , MAP Quinase Quinase 6/genéticaRESUMO
Se realiza un estudio de tipo documental, retrospectivo, transversal. La población del presente estudio estuvo representada por un total de 9.000 historias diagnosticadas en el Laboratorio Central de Histopatología Bucal "Dr. Pedro Tinoco" de la Facultad de Odontología de la U.C.V., durante el período 1988-2008. La muestra evaluada quedó conformada por un total de Cuatro Mil Ciento Sesenta y Seis (4.166) casos, los cuales fueron seleccionados de manera intencional no probabilística a partir de la población antes mencionada siguiendo criterios de inclusión y exclusión. La prevalencia de Lesiones Benignas y Desórdenes Potencialmente Malignos que afectan la Mucosa Bucal es alta (46,2%) con respecto a la muestra total estudiada (9000 casos). De acuerdo al Grupo Etario observamos un intervalo de edad entre 15 y 97 años, una media de 47,3 años y Desv. Tip de 16,5 (Y ± s : 47,3 ± 16,5). En relación a la distribución por Género, en nuestro estudio existe un predominio de las lesiones de la mucosa bucal por el sexo femenino (69,7%). En base al diagnóstico clínico se identificaron 77 lesiones diferentes. El Fibroma Traumático fue la lesión más común con 1042 casos (25,01%), seguida por la Leucoplasia con 764 casos (18,33%), la Hiperplasia Fibrosa por Prótesis Dental con 447 casos (10,73%). En referencia a las diferentes localizaciones anatómicas mayormente afectadas en este estudio: el Reborde Alveolar ocupó el primer lugar (1134 casos; 27,2%), seguida por Los Carrillos (639 casos; 15,33%), Labio Inferior (522 casos; 12,5%), Encías (493 casos; 11,8%).En referencia al grado de Concordancia global entre el Diagnóstico Clínico e Histopatológico fue del 75,9 % de los casos (3.161 casos de 4.166). Situación que nos permite asumir que la concordancia global es satisfactoria.
A study of documentary, retrospective, cross. The study population was represented by a total of 9,000 stories diagnosed at the Central Laboratory of Oral Histopathology "Dr. Pedro Tinoco " in the Faculty of Dentistry at UCV, during the period 1988-2008 . The sample studied was composed of a total of Four Hundred Sixty Six Thousand (4,166 ) cases , which were selected intentionally not random from the population above following inclusion and exclusion criteria . Injury prevalence Benign and Potentially Malignant Disorders affecting Mucosa is high ( 46.2 %) compared to the total study sample (9000 cases). According to Age Group observed an age range between 15 and 97 years , an average of 47.3 years and 16.5 Desv.Tip (Y ± s : 47.3 ± 16.5). Regarding the Gender distribution in our study there is a prevalence of oral mucosal lesions in females (69.7 %). Clinical diagnoses based on 77 different lesions were identified. The Traumatic fibroma was the most common injury in 1042 patients (25.01%), followed by leukoplakia with 764 cases (18.33%), Fibrous Hyperplasia By Dental Implants with 447 cases (10.73%). Referring to different anatomical locations most affected in this study: Alveolar Flange ranked first (1134 cases , 27.2 %), followed by The Cheeks (639 cases , 15.33%), Lower Lip (522 cases; 12.5%), Gum (493 cases, 11.8%). Referring to the degree of overall concordance between the Clinical and Histopathological diagnosis was 75.9% of cases (3,161 of 4,166 cases). This situation allows us to assume that the overall agreement is satisfactory.
Assuntos
Humanos , Masculino , Adulto , Feminino , Adulto Jovem , Fibromatose Gengival/patologia , Leucoplasia Oral/patologia , Mucosa Bucal/anatomia & histologia , Mucosa Bucal/lesões , Diagnóstico Bucal , Doenças da Boca , Cirurgia BucalRESUMO
El Fibromixoma Odontogénico es una variante del Mixoma Odontogénico. Se describe como una lesión intraósea agresiva derivada del tejido conjuntivo embrionario asociada con la odontogénesis1 constituida principalmente por grandes cantidades de tejido fibroso celular maduro. Su origen es controvertido, aparece en el esqueleto facial, afectando con mayor frecuencia a la mandíbula2. A continuación se presenta el caso clínico de un paciente de sexo femenino de 36 años de edad que presentó un aumento de volumen a nivel del ápice de diente 1.6 ,en la que se realizó un curetaje logrando la completa resección de la lesión, el resultado del informe patológico da el diagnóstico de Fibromixoma de origen Odontogénico
The Odontogenic Fibromyxoma is a variant of the Odontogenic Myxoma. It is described as an agressive intraoseous lesion that derives from the embrionary connective tissue associated with the odontogenesis, constituted by great amounts of celular mature fibrous tissue. It has a controverted origin, appears in the facial skeleton affecting more frecuently the mandible. We present a case of a 36 year old female who consulted with an increase of volume in relation to the 1.6 theet where we practiced a curetaje obtaining a complete resection of the lesion, the results of the patologic inform gives the diagnostic of odontogenic fibromyxoma
Assuntos
Feminino , Fibromatose Gengival/diagnóstico , Fibromatose Gengival/patologia , Mandíbula , Maxila/lesões , Mixoma/diagnóstico , Mixoma/patologia , OdontologiaRESUMO
Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (ANTXR2) located on chromosome 4q21. Characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. The present report describes a pair of sibs and three other JHF/ISH patients whose diagnoses were based on typical clinical manifestations and confirmed by histopathologic analyses and/or molecular analysis. A comparison of ISH and JHF, additional thoughts about new terminology (hyaline fibromatosis syndrome) and a modified grading system are also included.
Assuntos
Doenças do Tecido Conjuntivo/genética , Síndrome da Fibromatose Hialina/genética , Síndrome da Fibromatose Hialina/patologia , Proteínas de Membrana/genética , Criança , Pré-Escolar , Doenças do Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/cirurgia , Feminino , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Hiperplasia Gengival/genética , Hiperplasia Gengival/patologia , Humanos , Síndrome da Fibromatose Hialina/cirurgia , Masculino , Receptores de Peptídeos , Adulto JovemRESUMO
INTRODUCTION: Gingiva fibromatosis is a relatively rare condition characterized by diffuse enlargement of the gingiva, which is caused by expansion and accumulation of the connective tissue. OBJECTIVE: The aim of the present study was to investigate proliferative and apoptotic biomarker expression in normal gingiva and two forms of gingival fibromatosis. METHODS: Archived tissue specimens of hereditary gingival fibromatosis, gingival fibromatosis and dental abnormality syndrome and normal gingiva were subject to morphological analysis and immunohistochemical staining. The results were analyzed statistically. RESULTS: Proteins associated with proliferation were found in the nuclei of epithelial cells from the basal and suprabasal layers, whereas apoptotic proteins were detected in the cytoplasm of the upper layers of the epithelium. Increased expressions of minichromosome maintenance proteins 2 and 5 were observed in the gingival fibromatosis and dental abnormality syndrome samples. In contrast, geminin expression was higher in normal gingiva samples. No difference in the expression of apoptotic proteins was observed among the groups. CONCLUSION: Our findings support a role for augmented proliferation of epithelial cells within the overgrown tissues associated with gingival fibromatosis or dental abnormality syndrome. However, our data suggest that different biological mechanisms may account for the pathogenesis of different types of gingival fibromatosis.
Assuntos
Proteínas de Ciclo Celular/análise , Células Epiteliais/química , Fibromatose Gengival/metabolismo , Proteínas Nucleares/análise , Anormalidades Dentárias/metabolismo , Biomarcadores/análise , Estudos de Casos e Controles , Estudos Transversais , Células Epiteliais/patologia , Feminino , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Geminina , Humanos , Imuno-Histoquímica , Masculino , Componente 2 do Complexo de Manutenção de Minicromossomo , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologia , Proteína X Associada a bcl-2/análiseRESUMO
Zimmermann-Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, hypertrichosis, intellectual disability, and absence and/or hypoplasia of the nails or terminal phalanges of the hands and feet. The syndromic features of ZLS are highly variable and can overlap with other entities featuring gingival fibrosis. This study describes a patient with ZLS with novel findings, including colpocephaly, hemivertebra, polydactyly, hyperpigmentation, and hemihyperplasia. Thus, the present report expands the phenotypic spectrum of this uncommon syndrome.
Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/patologia , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/patologia , Fibromatose Gengival/diagnóstico , Fibromatose Gengival/patologia , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/patologia , Fenótipo , Criança , Feminino , HumanosRESUMO
INTRODUCTION: Gingiva fibromatosis is a relatively rare condition characterized by diffuse enlargement of the gingiva, which is caused by expansion and accumulation of the connective tissue. OBJECTIVE: The aim of the present study was to investigate proliferative and apoptotic biomarker expression in normal gingiva and two forms of gingival fibromatosis. METHODS: Archived tissue specimens of hereditary gingival fibromatosis, gingival fibromatosis and dental abnormality syndrome and normal gingiva were subject to morphological analysis and immunohistochemical staining. The results were analyzed statistically. RESULTS: Proteins associated with proliferation were found in the nuclei of epithelial cells from the basal and suprabasal layers, whereas apoptotic proteins were detected in the cytoplasm of the upper layers of the epithelium. Increased expressions of minichromosome maintenance proteins 2 and 5 were observed in the gingival fibromatosis and dental abnormality syndrome samples. In contrast, geminin expression was higher in normal gingiva samples. No difference in the expression of apoptotic proteins was observed among the groups. CONCLUSION: Our findings support a role for augmented proliferation of epithelial cells within the overgrown tissues associated with gingival fibromatosis or dental abnormality syndrome. However, our data suggest that different biological mechanisms may account for the pathogenesis of different types of gingival fibromatosis.