Gingival fibromatosis: clinical, molecular and therapeutic issues

Abstract

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. In severe cases, the excess tissue may cover the crowns of the teeth, thus causing functional, esthetic, and periodontal problems, such as bone loss and bleeding, due to the presence of pseudopockets and plaque accumulation. It affects both genders equally. Hereditary, drug-induced, and idiopathic gingival overgrowth have been reported. Hereditary gingival fibromatosis can occur as an isolated condition or as part of a genetic syndrome. The pathologic manifestation of gingival fibromatosis comprises excessive accumulation of extracellular matrix proteins, of which collagen type I is the most prominent example. Mutation in the Son-of-Sevenless-1 gene has been suggested as one possible etiological cause of isolated (non-syndromic) hereditary gingival fibromatosis, but mutations in other genes are also likely to be involved, given the heterogeneity of this condition. The most attractive concept of mechanism for drug-induced gingival overgrowth is epithelial-to-mesenchymal transition, a process in which interactions between gingival cells and the extracellular matrix are weakened as epithelial cells transdifferentiate into fibrogenic fibroblast-like cells. The diagnosis is mainly made on the basis of the patient’s history and clinical features, and on histopathological evaluation of affected gingiva. Early diagnosis is important, mostly to exclude oral malignancy. Differential diagnosis comprises all pathologies in the mouth with excessive gingival overgrowth. Hereditary gingival fibromatosis may present as an autosomal-dominant or less commonly autosomal-recessive mode of inheritance. If a systemic disease or syndrome is suspected, the patient is directed to a geneticist for additional clinical examination and specialized diagnostic tests. Treatments vary according to the type of overgrowth and the extent of disease progression, thus, scaling of teeth is sufficient in mild cases, while in severe cases surgical intervention is required. Prognosis is precarious and the risk of recurrence exists.

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

“…or occurs as an apparent isolated trait as non-syndromic hereditary gingival fibromatosis (HGF). 1 GF may also develop from environmental exposure such as a side effect of medications including anticonvulsants (i.e., phenytoin), immunosuppressants (i.e., cyclosporine), or calcium channel blockers (i.e., nifedipine, diltiazem, and verapamil). 2,3 The initial differential diagnosis for GF also includes chronic hyperplastic gingivitis, leukemic infiltrate, and some systemic diseases such as Crohn disease (MIM: 266600), neurofibromatosis (MIM: 162200), primary amyloidosis (MIM: 204850), sarcoidosis (MIM: 181000), scurvy (MIM: 240400), and Wegener granulomatosis (MIM: 608710) that have been associated with gingival overgrowth.…”

“…7 The estimated frequency of HGF is 1:175,000, equally affecting males and females. 1 The surgical treatment, gingivectomy with gingivoplasty, can be applied to individuals with massive gingival enlargement in cases of aesthetic concern; nevertheless, the recurrence of hyperplasia is relatively high potentially because of the genetic predisposition especially in hereditary forms.…”

Gene expression profiling and bioinformatics analysis of hereditary gingival fibromatosis

“…GF may co-exist with various genetic syndromes, such as Rutherfurd syndrome, Cowden syndrome, Zimmerman-Laband syndrome, Murray-Puretic syndrome and hyaline fibromatosis syndrome, or occurs as an apparent isolated trait as non-syndromic hereditary GF (HGF) (1,(4)(5)(6). HGF, also known as hereditary gingival hyperplasia or idiopathic gingival fibromatosis, is the most common genetic form of GF that is typically transmitted as an autosomal-dominant trait (7,8).…”

“…HGF, also known as hereditary gingival hyperplasia or idiopathic gingival fibromatosis, is the most common genetic form of GF that is typically transmitted as an autosomal-dominant trait (7,8). HGF affects males and females equally at an estimated incidence of 1 per 175,000 of the population (1,9). As HGF is rare and benign, and due to an increase in the number of non-surgical treatments, it is difficult to collect large samples of HGF.…”

“…Gingival fibromatosis (GF) is a rare condition of gingival overgrowth, characterized by a slowly progressive, benign, localized or generalized fibrous enlargement of maxillary and mandibular keratinized gingiva (1)(2)(3). GF may co-exist with various genetic syndromes, such as Rutherfurd syndrome, Cowden syndrome, Zimmerman-Laband syndrome, Murray-Puretic syndrome and hyaline fibromatosis syndrome, or occurs as an apparent isolated trait as non-syndromic hereditary GF (HGF) (1,(4)(5)(6).…”