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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.
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Fibromatose Gengival , Heterogeneidade Genética , Humanos , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Antígenos CD36/genética , Linhagem , Receptores Proteína Tirosina Quinases/genéticaRESUMO
OBJECTIVE: The aim of systematic review was to describe the phenotypes and molecular profiles of syndromes with gingival fibromatosis (GF). METHODS: A comprehensive search of PubMed, LILACS, Livivo, Scopus, and Web of Science was conducted using key terms relevant to the research questions and supplemented by a gray literature search. The Methodological Quality and Synthesis of Case Series and Case Reports in association with the Case Series and Prevalence Studies from the Joanna Briggs Institute critical appraisal tools were used for the risk of bias. We followed the PRISMA checklist guidelines. RESULTS: Eighty-four studies reporting GF as an oral manifestation of a syndrome were identified in this review. Enamel renal syndrome was the most frequently reported syndrome with GF, represented by 54 individuals in 19 studies, followed by Zimmermann-Laband syndrome with 24 individuals in 15 studies and Costello syndrome, which was presented in a case series study with 41 individuals. Among reported cases, other clinical manifestations such as hypertrichosis, ectopic gingival calcification, and cherubism were described. CONCLUSIONS: The results emphasize the need of systematic oro-dental-facial phenotyping for future descriptions as well as further molecular analysis in order to better understand the occurrence of syndromic GF.
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Anormalidades Múltiplas , Anormalidades Craniofaciais , Fibromatose Gengival , Deformidades Congênitas da Mão , Fibromatose Gengival/genética , Humanos , SíndromeRESUMO
Enamel renal syndrome (ERS) is a rare autosomal recessive disorder not fully characterized. Here we investigated ERS characteristics in 11 patients from 5 Brazilian families through clinical examination, imaging, renal ultrasonography, laboratory tests and DNA sequencing. The patients' age ranged from 6 to 25 years-old, and the presence of hypoplastic amelogenesis imperfecta, microdontia, intra-pulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicles, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis were common findings to all patients. Only 4 patients showed abnormal laboratory tests (vitamin D, parathyroid hormone, phosphate, calcium). Intellectual disability and renal cysts were present in 2 patients each. Biallelic loss of function mutation in FAM20A gene, characterized by one base pair deletion in exon 11, resulting in a frameshift replacing a glutamine at codon 483 for a lysine and terminating at position 24 [NG_029809.1: c.1447delG; p.(Glu483Lysfs*24)], was detected in all patients, strongly suggesting a founder effect. Our results reinforce the distinct orofacial features of ERS, which are the clue for kidney examination and genetic testing. Early diagnosis is essential to minimize the deleterious effects related to ERS. Here we report the largest series of patients with ERS in a same population, and describe, for the first time, a founder mutation for FAM20A.
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Amelogênese Imperfeita/genética , Proteínas do Esmalte Dentário/genética , Genética Populacional , Nefrocalcinose/genética , Adolescente , Adulto , Amelogênese Imperfeita/epidemiologia , Amelogênese Imperfeita/patologia , Brasil/epidemiologia , Criança , Éxons/genética , Feminino , Efeito Fundador , Mutação da Fase de Leitura/genética , Homozigoto , Humanos , Rim/metabolismo , Rim/patologia , Masculino , Nefrocalcinose/epidemiologia , Nefrocalcinose/patologia , Linhagem , Deleção de Sequência/genética , Adulto JovemRESUMO
INTRODUCTION: Hereditary gingival fibromatosis (HGF) is a rare disease characterized by gingival enlargement, normal color with benign and firm consistency. This growth may be exacerbated by use of drugs and plaque build-up. The treatment for this clinical condition is surgical excision of the enlarged gingival tissue or the extraction of all teeth. CASE REPORT: A 20-year-old Brazilian female handicapped patient with a chief complaint of exaggerated gingival enlargement who had been prescribed Carbamazepine and Gardenal was referred to our center. According to the clinical presentation and family history, the final diagnosis of gingival enlargement was HGF. Full dental treatment was performed, including basic periodontal treatment, restorations, sealants, and gingivoplasty with internal bevel. Special care was taken to ensure that there was no change in patient's anticonvulsant medication. The patient has been monitored for seven years without signs of recurrence of gingival hyperplasia due to constant professional and home control of plaque.
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La fibromatosis gingival es una enfermedad rara que se caracteriza por aumento del tejido gingival por proliferación fibrosa, es de crecimiento lento, cubriendo en algunos casos la totalidad de los dientes comprometidos. Esta nosología comprende un grupo heterogéneo de patologías de causas no determinadas. El objetivo de este trabajo es presentar un caso clínico de una paciente de 13 años con FGI Unilateral, su diagnóstico, tratamiento y seguimiento durante cuatro años. Presenta al examen clínico intraoral, agrandamiento anormal de su encía tanto superior como inferior, afectando solamente los hemiarcos del sector izquierdo. A la palpación es indolora y de consistencia fibrosa. No se encontraron factores locales que justifiquen dicho aumento. El examen físico elimina la posibilidad de otras patologías asociadas, no refiriendo recibir medicaciones inmunosupresivas, antiepilépticos o antihipertensivas. No tiene antecedentes familiares. La paciente fue sometida a extirpación quirúrgica del tejido hiperplasiado y el material obtenido enviado a estudio histopatológico. Después del tratamiento quirúrgico y una buena higiene oral con exámenes de control efectuados durante cuatro años no se observó recurrencia. A pesar de ser una patología poco frecuente el odontólogo debe conocer la fisiopatología y comprender que el manejo de ésta enfermedad es a través de un equipo multidisciplinario. El diagnóstico precoz y el tratamiento oportuno logran la recuperación psicológica, estética y funcional de los pacientes.
Gingival fibromatosis is a rare disease characterized by progressive enlargement of the gingiva caused by an increase in submucosal connective tissue. The enlargement may potentially cover the exposed tooth surfaces. Idiopathic gingival fibromatosis (IGF) is a heterogeneous group of disorders with no definite cause. The aim of this study is to present a 13-year-old female patient with unusual clinical forms of Unilateral FGI with a complete analysis of the features of the clinical diagnosis, treatment and follow-up for four years. Intraoral examination revealed severe gingival overgrowth involving both the upper arch and the lower arch, affecting on the left side. The right side of the mouth was unaffected. There was no significant pain. The lesion was diffuse, firm and fibrotic. Her medical and family history was also non-contributory. The patient was not receiving any antiepileptic, antihypertensive, or immunosuppressive medications that could contribute to the gingival enlargement. Histopathological examination showed hyperparakeratinized stratified squamous epithelium, presence of a thickened acanthotic epithelium and focal hyperplasia. Underlying connective tissue stroma was collagenous with numerous lymphoplasmacytic infiltrate. Unusual findings include the presence of calcified particles. Bevel gingivectomy was taken to remove gingival overgrowth. This case is thus a rare and atypical presentation of gingival fibromatosis. The patient was advised to maintain good oral hygiene to minimize the effect of inflammation on fibroblasts. In our case, even after four years of follow-up, no recurrence of gingival overgrowth was observed. Unilateral IGF is a relatively rare condition with poorly understood etiopathogenesis and recurrence rates. The cases should be treated with a multidisciplinary management. Treatment appreciably improved the patient's psychological, aesthetics and masticatory competence.
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Humanos , Feminino , Adolescente , Fibromatose Gengival/diagnóstico , Gengivectomia , Gengivoplastia , Radiografia Panorâmica , Tomografia Computadorizada por Raios X , Fibromatose Gengival/cirurgia , Má OclusãoRESUMO
The gingival fibromatosis is a slow and progressive benign proliferation, which affects the gingival tissues. It may present a genetic inheritance and association with some syndromes. There are conservative and radical treatments, ranging from hygiene care to bloc resection of the affected bone. This case scenario is a 07 year-old child, who presented a nodular unilateral hyperplastic lesion in the right mandible, with sessile base and approximately 5 cm in its largest diameter. The patient presented difficulty of lip closure and slight swelling in the right area of the face. The tomographic image showed infiltration in buccal and lingual cortical of right mandible and tooth displacement. After lesion removal, the histopathologic diagnosis of fibromatosis was confirmed, with no relapse after 20 months of follow-up.
A Fibromatose Gengival é uma proliferação benigna, lenta e progressiva, que afeta os tecidos gengivais. Pode apresentar herança genética e associação à uma série de síndromes. Existem tratamentos conservadores e radicais, desde cuidados com higiene à ressecção em bloco do tecido ósseo afetado. Este é o caso clínico de uma criança, que apresentou lesão hiperplásica unilateral em mandíbula, com deslocamento dentário. Após remoção, o diagnóstico de hiperplasia gengival foi confirmado e não há recidiva da lesão até o momento.
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Humanos , Feminino , Criança , Fibromatose Agressiva , Fibromatose Gengival , Hiperplasia GengivalRESUMO
Introduction: Hereditary gingival fibromatosis (HGF) is a rare condition presenting varied degrees of gingival enlargement. HGF can present as an isolated entity or as part of a syndrome. Current literatures report a defect in the Son of sevenless-1 gene (SOS-1) on chromosome 2p21-p22 (HGF1) as a possible cause of this condition. Case report: A case of a 16-year-old female is reported who presented generalized extensive gingival overgrowth, involving the maxillary and mandibular arches covering almost two thirds to three quarters of all teeth. Diagnosis of HGF was substantiated by the patient's clinical features, family history and histopathological examination. Treatment was excision of the gingival tissue by a modified gingivectomy technique with both manual instrumentation and electrosurgery. The postoperative course was uneventful and the patient's aesthetic concerns were addressed. Post-surgical follow-up after 18 months demonstrated no recurrence. Conclusion: Hereditary gingival fibromatosis stands apart from other gingival enlargements in the varied treatment options available and the nature of recurrence post treatment. There is no consensus among authors related to the mode of treatment. Here, in this present case report we highlight a novel surgical technique to deal with the extensive nature of enlargement seen in HGF cases.
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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.
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Feminino , Humanos , Masculino , 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 , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Imuno-Histoquímica , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologia , /análiseRESUMO
La fibromatosis gingival es una deformidad desarrollada de baja prevalencia. Las características clínicas de la FG incluyen tejidos gingivales hiperplásicos de consistencia firme y nodular, presentándose en forma generalizada o localizada. Las características histológicas de la FG incluyen principalmente tejido conectivo con un denso infiltrado rico en fibras de colágeno y un epitelio denso con papilas epiteliales largas. Se presenta un reporte de caso de un paciente masculino de 12 años referido para su tratamiento al servicio de Periodoncia e Implantes dentales de la Clínica Estomatológica Central de la Universidad Peruana Cayetano Heredia.
Gingival fibromatosis is a developed deformity with low prevalence. The clinical features of FG include hyperplastic gingival tissues usually firm and nodular, occurring in a generalized or localized form. The histologic features of FG mainly include connective tissue with a dense infiltrate rich in collagen fibers and dense epithelium with epithelial papillae long. This is a case report of a male patient of 12 years referred for treatment to a Periodontics and Implants Service of the Central Dental Clinic of the Cayetano Heredia Peruvian University.
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Humanos , Masculino , Criança , Fibromatose Gengival , Fibromatose Gengival/diagnóstico , Fibromatose Gengival/terapia , Crescimento Excessivo da GengivaRESUMO
A fibromatose gengival hereditária (FGH) é uma condição bucal rara, caracterizada clinicamente pelo crescimento contínuo e progressivo do tecido gengival. O crescimento gengival severo causa comprometimento estético/funcional, tendo como sinais clínicos comuns diastemas, mau posicionamento dentário e proeminência labial. Este relato de caso descreve o tratamento cirúrgico em duas etapas de um paciente que se apresentou à Universidade de São Paulo (FOUSP) queixando-se do aspecto antiestético ao sorrir, devido ao aumento gengival. A primeira etapa consistiu em um retalho parcial com excisão de margem gengival (remoção de altura/espessura do tecido conjuntivo). Na segunda etapa, foi realizado um retalho total associado à excisão de margem, para obter acesso ao tecido ósseo e melhorar o contorno da margem gengival. O pós-operatório mostrou uma reparação satisfatória, com um padrão da margem gengival e da crista-óssea compatível com a saúde periodontal e de acordo com as expectativas estéticas do paciente. A avaliação histológica das biópsias gengivais confirmou o diagnóstico clínico de FGH. Considerando as limitações de um relato de caso, coloca-se uma alternativa viável para demonstrar que a associação dessas técnicas, desde que bem indicadas, é uma possível abordagem cirúrgica para o restabelecimento estético/funcional dos pacientes com FGH.
Hereditary gingival fibromatosis (HGF) is a rare buccal condition, characterized by a continuous and progressive enlargement of the maxilary and mandibular gingiva. The severe gingival overgrowth causes functional and aesthetic problems with common clinical aspects as diastemas, irregular dental positioning and labial prominence. This article describes the surgical treatment in 2 stages of a man who presented himself at the University of São Paulo (FOUSP) complaining of unfavorable smile sapect due to the gingival overgrowth. First stage consisted of a partial flap with internal bevel incision to remove height/thickness of the connective tissue. In the second stage mucoperiostal flaps with internal bevel incision were made to access the bone and to improve the contour of the gingival tissue. The postoperative course showed a satisfatory healing with a compatible relation between gingival tissue/bone crest, periodontal health and the aesthetic expectations of the patient. Histological examination of gingival specimens supported the clinical diagnosis of HGF. Considering the limitations of a case report, na alternative is presented to demonstrate the association of surgical techniques if well indicated and a possible surgical approach for functional and aesthetic reestablishment of the patients with HGF.
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Humanos , Masculino , Adulto , Fibromatose Gengival/cirurgia , Hiperplasia Gengival , Gengivectomia , Diastema , Estética Dentária , Procedimentos Cirúrgicos BucaisRESUMO
A Fibromatose Gengival Hereditária (FGH) é descrita como uma condição bucal rara, clinicamente manifestada por um crescimento lento, progressivo, difuso e benigno dos tecidos gengivais. Alguns autores defendem a hipótese de o aumento gengival ser transmitido por um gene autossômico dominante, porém outros mostram que a FGH parece ser transmitida por um gene autossômico recessivo, em que pessoas não afetadas transmitemessa anormalidade a seus descendentes. O modo de transmissão hereditária parece ser autossômicodominante, relacionado ao cromossomo 2p21. A FGH pode se manifestar, de um modo geral, em duas situações diferentes: a primeira, quando o crescimento exagerado da gengiva constitui a única alteração patológica clinicamente observável, e a segunda, quando a fibromatose gengival é uma das alterações que se manifesta associada a outras patologias sistêmicas, como o retardo mental, a epilepsia, a hipertricose e a surdez progressiva. Através de uma revisão da literatura, este trabalho buscou elucidar todas as suas características, objetivando facilitar sua identificação, tratamento e controle
Hereditary gingival fibromatosis (HGF) is described as a rare oral condition, clinically manifested by a slow, progressive and benign enlargement of gingival tissues. Some authors support the hypothesis that HGF is transmitted by an autosomal dominant gene, while others think that HGF seems to be transmitted by an autosomal recessive gene, when non-affected subjects transmit this abnormality to their descendants. Thehereditary transmission mode seems to be an autosomal dominant inheritance related to the chromosome 2p21. In general, HGF can be observed in two different clinical situations: the first, when the exaggerated growth of the gingiva constitutes the only clinical pathological alteration observable and the second, when gingival fibromatosis associates with other systemic conditions, such as mental retardation, epilepsy, hypertrichosis and gradual deafness. The aim of this study was to review the literature on hereditary gingival fibromatosis and describe its characteristics to enable the diagnosis, treatment and control of this disease
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Crescimento Excessivo da Gengiva , Fibromatose Gengival , Fibromatose Gengival/diagnóstico , Fibromatose Gengival/terapia , Gengiva/anormalidades , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/terapiaRESUMO
O objetivo do presente trabalho é analisar os componentes celulares e de fibras do tecido conjuntivo nas hiperplasias inflamatórias (HI), nos fibromas (F) e na fibromatose gengival hereditária (FGH), além de investigar a imunocompetência e efetuar análises moleculares de pacientes com FGH. Para atingir os objetivos foram desenvolvidos 4 artigos, com diferentes metodologias e universos amostrais. No 1° artigo, pretendeu-se estabelecer critérios microscópicos validos para diferenciar F e HI. Foram avaliadas em microscópio óptico 136 lesões coradas pela Hematoxilina-eosina (HE) e pelo Tricrômico de Masson quanta às características microscópicas. Os resultados mostraram que uma área central de fibras colágenas dispostas de forma enovelada e mais densa, circundada por uma camada de fibras dispostas de forma paralela são características dos F, enquanto a presença de hiperplasia epitelial, infiltrado inflamatório e fibras colágenas organizadas de forma paralela são características das HI. Tais resultados motivaram o 2° artigo, no qual estudamos 18 lesões de F e 13 de HI, que foram preparadas histologicamente e coradas pelo picrosírius red e pelo direct blue para avaliação quantitativa das fibras colágenas e de fibras do sistema elástico, respectivamente, em microscopia a laser confocal. Os resultados confirmaram a disposição estrutural das fibras colágenas observada no 1° artigo, além de apontarem diferenças nas áreas ocupadas pelas fibras colágenas em todas as regiões estudadas. A fim de proceder a uma avaliação dos componentes fibroso e celular das 3 lesões fibrosas, foi desenvolvido o 3° artigo. Especimes das 3 lesões foram estudados em microscopia ótica, a fim de avaliar suas populações de fibroblastos e de células inflamatórias e os seguintes componentes fibrosos do tecido conjuntivo...
The objective of this study was to analyze the cellular and fibrous components of connective tissue in inflammatory hyperplasia (IH), oral fibroma (OF) and hereditary gingival fibromatosis (HGF), and to investigate the immuno competence and to perform molecular analysis in HGF patients. To achieve the goals were developed 4 articles, with different methodologies and sample universes. In the 1st article, we intended to establish microscopic criteria to differentiate F and IH. The microscopic characteristics of the lesions (n=136) stained by hematoxylin-eosin (HE) and Masson trichrome were evaluated in an optical microscope. The results showed that a central area of wound collagen fibers and arranged in a higher density, surrounded by a layer of parallel fibers are characteristic of F, while the presence of epithelial hyperplasia, inflammatory infiltrate and parallel collagen fibers are characteristics of HI. These results led the 2nd article, which studied 18 F and 13 and IH, histologically prepared and stained by picrosirius red and direct blue for the direct quantitative assessment of collagen fibers and elastic fibers of the system, respectively, in the confocal laser microscope. The results confirmed the structural arrangement of collagen fibers found in Article 1, and indicate differences in the areas of collagen fibers in all regions studied. In order to evaluate the cellular and fibrous components of the 3 fibrous lesions, was developed the 3rd article. Specimens of the 3 lesions were studied in optical microscopy, to assess their populations of fibroblasts and inflammatory cells and the following components of fibrous connective tissue: collagen fibers, elastic fiber system, reticular fibers and oxytalan fibers. The results showed different arrangement and concentration of collagen fibers in the 3 lesions and a higher concentration of reticular fibers in HGF. The analysis of...