Hereditary Gingival Fibromatosis

Hereditary gingival fibromatosis (HGF) is rare disease that is characterized by a benign, slowly progressive, fibrous enlargement of maxillary and mandibular keratinized gingiva. HGF is a genetically heterogeneous condition,the incidence and severity of the disease appear to depend on the penetrance and expressivity of the mutated gene. It can be divided into two types according to the clinical feature:the non-syndromic forms, which affect only gingiva,and the syndromic forms, which have rare systemic syndrome accompanied by gingival enlargement.The syndromic forms of HGF have been reported in Zimmerman-Laband syndrome,Rutherford syndrome,Cross syn- drome,Ramon syndrome,Cowden syndrome,Jones syndrome and so on. The non- syndromic forms are in association with hypertrichosis, and/or mental retardation, and/or epilepsy.The gingival enlargement usually begins at the time of eruption of the permanent dentition but can develop with the eruption of the primary dentition. It is rarely present at birth. Enlargement can affect the interdental papilla,marginal gingiva,attached gingiva and mucogingival junction.The Enlarged gingiva, which is non- haemorragic and asymptomatic, may be normal in color or erythematous and has a firm consistency with abundant stippling. Gingival excess results in pseudopocketing and periodontal problems, due to difficulties in daily oral hygiene. The gingival enlargement may cover part of the teeth or up to their occlusal surfaces. The most common effects related to the gingival lesions are diastemas, malpositioning of the teeth and prolonged retention of primary teeth, as well as delayed eruption of permanent or primary teeth, which has a bad effct on the function,speech and aesthetics.Histologically, the epithelium is dense, with elongated papillae and hyper- keratosis. The fibrous connective tissue presents bundles of coarse collagenous fibres with young fibroblasts and scarce blood vessels. Moreover, Small calcified particles,islands of osseous metaplasia,ulceration of the overlying mucosa,deposition of amyloid,islands of odontogenic epithelium and abundant neuro- vascular bundles have also been reported. HGF can affect only the gingiva, so the alveolar bone is intact and there are some impacted teeth in both arches on the radiographs.The main character of HGF is increasing synthesis and decreasing degradation of extracellular matrix (ECM), leading to accumulation of ECM. Myofibroblast,transforming growth factorβ(TGF-β),connective tissue growth factor(CTGF/CCN2),matrix metalloproteinase (MMPs) and sex hormone have relationship with the metabolism of ECM.When myofibroblast are activated, they can synthesize high-level extracellular matrix proteins, especially the collagen. TGF-β1,CTGF,and IFN-γcan influence the activation and transdifferentiation of myofibroblast. CCN2/CTGF is a matricellular factor associated with fibrosis that plays an important role in the production and maintenance of fibrotic lesions. CTGF/CCN2 is expressed both in the connective tissue stroma and in gingival epithelial cells in vivo in fibrotic tissues. TGF-βis a multifunctional cytokine known to be important in both wound healing and fibrotic process. The change of isoforms disturbs the balance of them, which can promote the synthesis of the ECM. Most TGF-βis produced in a latent form, so the mechanisms that activate TGF-βmay also play a key role in HGF. MMPs play an important role in degradation of ECM. Its activation and inhibition can be induced by TIMPs. TGF-β1 can regulate gene expression of MMPs and TIMPs. Dihydrotestosterone is a potent metabolite resulting from metabolism of testosterone. It can downregulate the production of interleukin-6 (IL-6) and increase the synthesis of TGF-β1.They promote the proliferation of fibroblast, increase the synthesis of ECM and decrease the degradation, which contribute to the gingival overgrowth.To date, Three loci have been mapped in familial cases with non- syndromic HGF: 2p21-p22,5q13-q22,2p22.3-p23.3;The gene loci related to syndromic HGF are 17q11.2,11p13.3,4q21,2p13-p21,7q and so on. SOS1 has been identified and cloned as etiologic factor for non-syndromic HGF, Whose mutation is related to increasing of fibroblast and the changing of ECM. The mutational SOS1 protein has enhanced activity and function.The mechanism of SOS1's mutation leading to the gingival enlargement is related to SOS1-Ras-ERK1/2 pathway.besides, the region at 5q13-q22 encompasses the calcium/ calmodulin- dependent protein kinase IV (CaMKIV) gene that is expressed in gingival. Genes for sodium/calcium exchanger (NCX1) and calmodulin-2 reside within the chromosome 2p21 interval that co-segregates with HGF. Some scholar presumed that abnormal Ca2+ signaling is involved in gingival overgrowth.The diagnosis of HGF is based on Hart's standard. The suggested treatments vary according to the degree of severity. When the enlargement is minimal, good scaling of teeth and home care may be sufficient to maintain good oral health. As the excess tissue increases, gingivectomy and gingivoplasty is necessary. According to the study of HGF's pathogenesis,some medicine which can interrupt the pathogenesis in the molecular level, such as IFN-γ,BMP-7 and HGF, can have an effect on HGF's therapy.There is no consensus regarding the timing for surgery.Some clinicians have suggested that the best time to perform surgery is when all the permanent teeth have erupted, others think that surgery should be performed at the early stage. Recurrence is related to the oral hygiene. Because of the inscrutability of the recurrence, the patient should recheck regularly after surgery. Treatment of such cases involves close collaboration between the practitioners of several dental specialties.Case report: case history: Generalized gingival swelling started at the time of eruption of the permanent dentition, and it has slowly progressed for 13 years. There was no family history of such a disorder. She was healthy without systemic history and denied taking any medication. Clinical examination: She didn't have any problem about intelligence.The hair and eyebrows were dense with beard and hypertrichosis of face and limbs. The centre of the palm and foot plate were soft,Whose dermal ridge were more and deeper.She had difficulty in closing his lips because of the severely enlarged gingival tissues. The labial,lingual and palatal gingiva of maxilla and mandible enlarged, which affected the interdental papilla,marginal gingiva,attached gingiva and mucogingival junction. The gingival enlargement may cover part of the anterior teeth and up to the occlusal surfaces of the posterior teeth in both arches.The enlarged gingiva, which was non-haemorragic, was normal in color and had a firm consistency with abundant stippling. On the radiographs, alveolar bone was intact and the teeth were almostly normal in both arches, in which there were no missing teeth, and #22 didn't reach the occlusal surface. Diagnosis: Based on the noncontributory medical and family history, the absence of medication and the clinical findings, the patient was diagnosed as hereditary gingival fibromatosis.Therapy: after initial therapy, gingivectomy and gingivoplasty were carried out under local anaesthesia. After surgery, the healing was good, and the colour and form of gingiva were almost normal. Histological examination: The epithelium was dense, with elongated papillae and parakeratinization. The fibrous connective tissue presented bundles of coarse collagenous fibres with lots of inflammatory cell and scarce blood vessels. Sequester and bone tissue can be seen.