Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Animals ; Humans ; Mice ; Fibromatosis, Gingival/pathology* ; Gingiva ; Kinesins/genetics* ; Mutation/genetics* ; Phosphatidylinositol 3-Kinases/genetics*

Hereditary gingival fibromatosis (HGF) is a familial hereditary disease; while it is rare and usually benign, it is also characterized by the slow and progressive development of gingival tissue. This paper reports on the clinical examina-tion and history of HGF in a family of patients.
Fibromatosis, Gingival ; Gingiva ; Humans

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.
Amelogenesis Imperfecta* ; Amelogenesis* ; Cone-Beam Computed Tomography ; Dental Enamel Hypoplasia ; Dental Enamel* ; Dentists ; Fibromatosis, Gingival ; Humans ; Kidney Diseases ; Male ; Metabolic Diseases ; Nephrocalcinosis ; Nephrolithiasis* ; Phenotype ; Radiography ; Tooth ; Young Adult

Gingival fibromatosis is a rare disease, especially its syndromic form. Here, we review the literatures on gingival fibromatosis and briefly summarize some characters on clinical, etiological, genetic and histopathological aspects. We also present a rare case of gingival fibromatosis with multiple unusual findings in a 21-year-old man. And we differentiate it from some well-known syndromes including gingival fibromatosis. Maybe it implies a new syndrome within the spectrum of those including gingival fibromatosis.
Atrophy ; Bone Diseases, Developmental ; diagnosis ; Cataract ; congenital ; Cerebellum ; pathology ; Deafness ; diagnosis ; Diagnosis, Differential ; Fibromatosis, Gingival ; diagnosis ; Frontal Lobe ; pathology ; Gingival Overgrowth ; diagnosis ; Humans ; Male ; Maxillary Diseases ; diagnosis ; Young Adult

Hereditary gingival fibromatosis (HGF) is a rare hereditary condition characterized by a slow, progressive increase in the gingival tissue. A case of HGF was reported and relevant literature of HGF were reviewed.
Fibromatosis, Gingival ; Gingiva ; Humans ; Male

PURPOSE: It is well recognized that gingival enlargement is induced by unwanted effect associated with three major drugs/drug groups - phenytoin, cyclosporine, and the calcium channel blockers. The present case report describes the effect and limitation of non-surgical treatment in gingival enlargement cases. MATERIALS AND METHODS: Three cases included 2 drug-influenced gingival enlargement patients and a idiopathic gingival fibromatosis patient. For the drug-influenced gingival enlargement patients, the medication was replaced with other medication. And then, all the patients were treated non-surgically. RESULTS: Drug-influenced gingival enlargements had been reduced after non-surgical treatment and the results were well-maintained. In the idiopathic gingival fibromatosis case, non-surgical treatment resulted in only limited reduction of gingival enlargement, and surgical periodontal treatment was unavoidable. CONCLUSION: These case reports indicated that non-surgical periodontal treatment with change in medication was effective in the treatment of drug-influenced gingival enlargements. Non-surgical approach can be considered as the primary management to reduce the gingival enlargement. If non-surgical treatment encounters a limitation, surgical treatment should be considered
Calcium Channel Blockers ; Cyclosporine ; Fibromatosis, Gingival ; Humans ; Nifedipine ; Phenytoin

Fibromatosis, Gingival ; diagnosis ; Gingival Overgrowth ; diagnosis ; therapy ; Humans

OBJECTIVETo ascertain histology changes of hereditary gingival fibromatosis (HGF) and the location of HGF gene.

METHODSA pedigree analyses of HGF; and the ultrastructure of gingival overgrowth tissue was observed with electron microscopy. The overgrowth of the HGF gene was defined with microsatellite markers.

RESULTSThe connective tissue of HGF consisted of coarse collagen bundles and several kinds of cells arranged abnormally, such as: epithelial cells, smooth muscle cells and so on; the HGF locus had been mapped to chromosome 5q13-q22.

CONCLUSIONSThe gingival pathologic changes resemble "hamartoma"; the findings has implications for identification of the underlying genetic basis of HGF.

Child ; Chromosome Mapping ; Chromosomes, Human, Pair 5 ; genetics ; Family Health ; Female ; Fibromatosis, Gingival ; genetics ; pathology ; ultrastructure ; Genetic Predisposition to Disease ; genetics ; Gingiva ; metabolism ; pathology ; ultrastructure ; Humans ; Male ; Microsatellite Repeats ; Microscopy, Electron ; Pedigree

Idiopathic gingival fibromatosis is associated with other abnorma ities of which the most striking is hypertrichosis of variable degree. Gorlin and Pindborg described this condition as a distinct syndrome termed idiopathic gingival fibromatosis and hypertrichosis. We report a case of idiopathic gingival fibromatosis and hypertrichosis occuring in 34-year-old woman with enlarged gingival tissue, hypertrichosis, and enlargenment of the breasts, ears and nose. Laboratory tests including hormonal and chromosomal studies were all within normal limits. Histologically, the gingival hyperplastic tissue showed thick bundle of collagen fibers with few fibroblasts or capillaries and little or no inflammatory infiltrate.
Adult ; Breast ; Capillaries ; Collagen ; Ear ; Female ; Fibroblasts ; Fibromatosis, Gingival* ; Humans ; Hypertrichosis* ; Nose ; Strikes, Employee

Idiopathic gingival fibromatosis is associated with other abnorma ities of which the most striking is hypertrichosis of variable degree. Gorlin and Pindborg described this condition as a distinct syndrome termed idiopathic gingival fibromatosis and hypertrichosis. We report a case of idiopathic gingival fibromatosis and hypertrichosis occuring in 34-year-old woman with enlarged gingival tissue, hypertrichosis, and enlargenment of the breasts, ears and nose. Laboratory tests including hormonal and chromosomal studies were all within normal limits. Histologically, the gingival hyperplastic tissue showed thick bundle of collagen fibers with few fibroblasts or capillaries and little or no inflammatory infiltrate.
Adult ; Breast ; Capillaries ; Collagen ; Ear ; Female ; Fibroblasts ; Fibromatosis, Gingival* ; Humans ; Hypertrichosis* ; Nose ; Strikes, Employee