Clinics and genetic background of hereditary gingival fibromatosis

Background Hereditary gingival fibromatosis (HGF) is a rare condition characterized by slowly progressive overgrowth of the gingiva. The severity of overgrowth may differ from mild causing phonetic and masticatory issues, to severe resulting in diastemas or malposition of teeth. Both, autosomal-dominant and autosomal-recessive forms of HGF are described. The aim of this review is a clinical overview, as well as a summary and discussion of the involvement of candidate chromosomal regions, pathogenic variants of genes, and candidate genes in the pathogenesis of HGF. The loci related to non-syndromic HGF have been identified on chromosome 2 (GINGF, GINGF3), chromosome 5 (GINGF2), chromosome 11 (GINGF4), and 4 (GINGF5). Of these loci, pathogenic variants of the SOS-1 and REST genes inducing HGF have been identified in the GINGF and the GINGF5, respectively. Furthermore, among the top 10 clusters of genes ranked by enrichment score, ATP binding, and fibronectin encoding genes were proposed as related to HGF. Conclusion The analysis of clinical reports as well as translational genetic studies published since the late’90s indicate the clinical and genetic heterogeneity of non-syndromic HGF and point out the importance of genetic studies and bioinformatics of more numerous unrelated families to identify novel pathogenic variants potentially inducing HGF. This strategy will help to unravel the molecular mechanisms as well as uncover specific targets for novel and less invasive therapies of this rare, orphan condition.

Idiopathic pigmented gingival fibromatosis: A case report

Gingival fibromatosis is a rare and heterogeneous group of disorders that develop as slowly progressive, local or diffuse enlargements within marginal and attached gingiva or interdental papilla. Gingival fibromatosis is a condition that can occur as an isolated disease or as a part of a syndrome or chromosomal abnormality. Here, we present the case of a 28-year-old male with pigmented gum enlargement in the maxilla and mandible. The clinical, radiographic, and histopathological features have been described in detail.

Pathogenesis of Enamel-Renal Syndrome Associated Gingival Fibromatosis: A Proteomic Approach

The enamel renal syndrome (ERS) is a rare disorder featured by amelogenesis imperfecta, gingival fibromatosis and nephrocalcinosis. ERS is caused by bi-allelic mutations in the secretory pathway pseudokinase FAM20A. How mutations in FAM20A may modify the gingival connective tissue homeostasis and cause fibromatosis is currently unknown. We here analyzed conditioned media of gingival fibroblasts (GFs) obtained from four unrelated ERS patients carrying distinct mutations and control subjects. Secretomic analysis identified 109 dysregulated proteins whose abundance had increased (69 proteins) or decreased (40 proteins) at least 1.5-fold compared to control GFs. Proteins over-represented were mainly involved in extracellular matrix organization, collagen fibril assembly, and biomineralization whereas those under-represented were extracellular matrix-associated proteins. More specifically, transforming growth factor-beta 2, a member of the TGFβ family involved in both mineralization and fibrosis was strongly increased in samples from GFs of ERS patients and so were various known targets of the TGFβ signaling pathway including Collagens, Matrix metallopeptidase 2 and Fibronectin. For the over-expressed proteins quantitative RT-PCR analysis showed increased transcript levels, suggesting increased synthesis and this was further confirmed at the tissue level. Additional immunohistochemical and western blot analyses showed activation and nuclear localization of the classical TGFβ effector phospho-Smad3 in both ERS gingival tissue and ERS GFs. Exposure of the mutant cells to TGFB1 further upregulated the expression of TGFβ targets suggesting that this pathway could be a central player in the pathogenesis of the ERS gingival fibromatosis.In conclusion our data strongly suggest that TGFβ -induced modifications of the extracellular matrix contribute to the pathogenesis of ERS. To our knowledge this is the first proteomic-based analysis of FAM20A-associated modifications.

Case Report: A Case of Hereditary Gingival Fibromatosis With a High Level of Human β Defensins in Gingival Epithelium

Hereditary gingival fibromatosis [HGF, (MIM 135300)], a rare benign oral condition, has several adverse consequences such as aesthetic changes, malocclusion, speech impediments, and abnormal dentition. However, relatively few studies have addressed the beneficial effects of thick gingival tissues in resisting external stimuli. In this report, we present a unique case of a family affected by HGF that manifests as a ‘healthy’ gingiva. Human β-defensins (hBDs) are known to play a pivotal role in the clearance and killing of various microbes, and contribute to maintaining a healthy oral environment, which is currently emerging research area. However, the expression pattern and localisation of hBDs in patients with HGF have not yet been reported. hBD-2 and hBD-3 in the pedigree we collected had relatively elevated expression. High hBD levels in the gingival tissue of patients from the family may be beneficial in protecting oral tissue from external stimuli and promoting periodontal regeneration, but their role and the mechanisms underlying HGF need to be clarified.

Seven-year follow-up of a patient with hereditary gingival fibromatosis treated with a multidisciplinary approach: case report

Background Hereditary gingival fibromatosis (HGF) is rare in clinical practice, and the long-term results of the combined orthodontic-periodontal treatment of HGF are rarely reported. Case presentation This study reports for the first time the results of seven years of follow-up in a seven-year-old girl with HGF. The diagnosis was confirmed by clinical signs, family history and histopathological examination. First, periodontal scaling and oral hygiene reinforcement were performed regularly in the mixed dentition stage. Next, gingivoplasty was performed on the permanent dentition. Two months after the surgery, treatment with fixed orthodontic appliances was conducted. The teeth were polished on a monthly basis, and oral hygiene was reinforced to control gingival enlargement. Gingival hypertrophy recurred slightly, and gingivectomies were performed in the months following the start of orthodontic treatment. Follow-up was performed for 24 months with orthodontic retention, and gingival enlargement remained stable after the combined treatment. Conclusions The risk of gingival hyperplasia recurrence during and after orthodontic treatment is high, but satisfying long-term outcomes can be achieved with gingivectomy, malocclusion correction, and regular follow-up maintenance.

Hereditary gingival fibromatosis: A Case Report.

Introduction: Hereditary gingival fibromatosis is a rare disorder with a genetic component that may appear during tooth replacement. This condition can cause functional and aesthetic pro-blems such as malocclusions, diastemas, pain when chewing, dental caries, periodontal disease, delayed eruption, among others. Objective: To report the multidisciplinary treatment provided to a patient with hereditary gingival fibromatosis. Case Report: This report describes the treatment carried out in a thirteen-year-old male patient presenting generalized increase in gingival volume associated with functional and aesthetic compromise and delayed eruption of permanent teeth. After diagnosis, a multidisciplinary intervention was proposed, involving perio-dontal and pediatric dentistry procedures, which improved the quality of life of the patient both functionally and aesthetically. Conclusion: Hereditary gingival fibromatosis not only affects the dental eruption process, but also causes aesthetic and emotional alterations in the patient. The periodontal procedures significantly im-proved the appearance, function, and the psychological state of the patient.

Unique Clinical Features of Hereditary Gingival Fibromatosis Withelevated Expression of Human β-Defensin-2 and -3 in Gingival Epithelia

Background: Hereditary gingival fibromatosis (HGF), a rare benign oral condition, has several adverse consequences such as aesthetic changes, malocclusion, speech impediments, and abnormal dentition . H owever, relatively few studies have addressed the beneficial effects of thick gingival tissues on resisting external stimuli. Patients with HGF commonly manifest a ‘healthy’ gingiva , and the aetiology and pathogenesis of this condition remain unclear. H uman β-defensins (hBDs) are known to play a pivotal role in the clearance and killing of various microbes and contribute to maintaining a harmonious oral environment, which is currently an emerg ing research focus. We previously performed an immunohistochemi cal analysis of gingival tissues from a multigenerational family with non-syndromic HGFs (NHGF) . However , the expression pattern and localisation of hBD-2 and - 3 in patients with NHGF has not been reported. Methods: Gingival tissue was paraffin embedding, sectioned, and then the expression and localisation of hBD-2 and -3 in the gingival epithelium of patients with HGF and normal individuals were compared using immunohistochemistry (IHC) with descriptive and quantitative analysis. Results: The immunohistochemical staining showed a statistically significant increase in hBD-2 and 3 in gingiva l tissue derived from patients with HGF. Conclusion: Our current findings provide evidence to support the novel hypothesis that certain gene mutations of the HGF lead to relatively elevated expression levels of hBDs, which may be beneficial in protect ing oral tissue from external stimuli and promot ing periodontal regeneration.

Periodontal Disease Associated with Genetic Disorders

The object of this chapter was to provide an overview including relevant research progress of some genetic disorders with periodontal manifestations. A number of genetic disorders increase patient susceptibility to periodontal disease, with the latter exhibit rather rapid and aggressive presentations. Periodontal disease, perhaps could be the first detectable sign of an undiagnosed genetic disorder. It is therefore important for dental practitioners to be familiar with genetic disorders and their impact on the periodontal tissues. This chapter reviews several genetic disorders that exhibit periodontal manifestations, including hereditary gingival fibromatosis, Papillon-Lefèvre syndrome, cyclic neutropenia, Ehlers-Danlos syndrome and hypophosphatasia.