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Hereditary gingival fibromatosis (HGF) is a rare, benign disorder characterized by slowly progressive fibrous overgrowth of the gingiva. To date, two loci have been mapped in familial cases with autosomal dominant non-syndromic HGF: GINGF (MIM 135300) on chromosome 2p21-p22 and GINGF2 (MIM 605544) on chromosome 5q13-q22. Of the two loci, only SOS1 (son of sevenless one, MIM 182530) gene underlying GINGF locus has been identified. Ascertainment of a large Chinese family has allowed the mapping of a novel locus to 2p22.3-p23.3, GINGF3. Haplotype construction and analysis localized the new locus to an 11.4-cM interval between markers D2S2221 (telomeric) and D2S1788 (centromeric). The maximum two-point limit of detection (LOD) score of 3.45 (theta=0) and multipoint LOD score of 5.00 for marker D2S390 strongly supported linkage to this region. Thus, this genetic interval is distal to and does not overlap with the previously described locus, GINGF, on 2p21-p22.

WOS: 000230547700007, PubMed ID: 16080296, Gingival fibromatosis, short stature, border-line IQ. facial dysmorphism and hepatomegaly. Gingival fibromatosis is a rare and benign disorder. The enlarged gingivae are firm and may Interfere with speech, closure of the lips, and mastication. We report a thirteen years old girl, with gingival fibromatosis referred to the periodontics clinics. Full mouth gingivectomy and gingivoplasty were performed. Medical investigation showed short stature, low-borderline IQ, facial dysmorphism. and hepatomegaly. Histological analysis revealed hyperplasia In the epithelial area and fibrotic appearance of gingival connective tissue with dense collagen fibre clusters. Pedigree analysis confirmed that mode of inheritance is autosomal recessive. According to the combination of clinical findings, this case report may represent a previously unreported syndrome.

Gingival fibromatosis is frequently an isolated condition, but rarely associated with certain illnesses, or uncommon syndromes.This work describes a young patient presenting cherubism, with perturbed consciousness and very hyperplastic gingiva covering the major part of the dental crowns.We recall the characteristic clinical features of cherubism. Outcome is generally favorable with regression of the swelling. The combination with gingival fibromatosis is a particular manifestation.

Juvenile hyaline fibromatosis ( JHF ) is a rare autosomal recessive disease characterized by papulonodular skin lesions, gingival hyperplasia, joint contractures, and bone lesions. The skin lesions may consist of multiple large tumors, commonly on the scalp and around the neck, and small pearly, pink papules and plaques on the trunk, chin, ears, and around the nostrils. Here, we report a 2-year-old boy with characteristic stiffness of the knees and elbows and pink confluent papules on the paranasal folds, and periauricular and perianal regions. He also had hard nodules all over the scalp and around the mouth, and severe gingival hyperplasia. The lesions were totally excised and clinicopathological diagnosis was JHF.

Gingival overgrowth is the enlargement of the attached gingiva due to an increased number of cells. The most prevalent types of gingival overgrowth in children are drug-induced gingival overgrowth, hereditary gingival fibromatosis (HGF), and neurofibromatosis I (von Recklinghausen disease). Gingival overgrowth induced by drugs such as phenytoin, nifedipine, and cyclosporin develops due to an increase in the connective tissue extracellular matrix. According to epidemiologic studies, it is more prevalent in male children and adolescents. There is an additive effect of those drugs on the degree of gingival overgrowth. Genetic heterogeneity seems to play an important role in the development of the disease. Functional difficulties, disfigurement, increased caries, and delayed eruption of permanent teeth are the main complications of drug-induced gingival overgrowth. HGF is the most common syndromic gingival enlargement in children. This autosomal dominant disease usually appears at the time of eruption of permanent dentition. Histologically, it is characterized by highly collagenized connective tissue. The most important complications are drifting of teeth, prolonged retention of primary dentition, diastemata, and poor plaque control. Neurofibromatosis I is an autosomal dominant disease more common in mentally handicapped individuals. Gingival overgrowth is caused by the formation of plexiform neurofibromas in the connective tissue of the gingiva. Plexiform neurofibromas are pathognomonic of the disease and consist of hypertrophic nerves arranged as lobules in the connective tissue. Complications of the disease are multiple and severe due to neurofibromas and their occasional malignant transformation.

Based on our accumulated experience, the present study evaluates and discusses the indications, advantages and inconveniences of oral cavity epulis resection using the carbon dioxide laser (CO2) versus the Erbium:YAG laser (Er:YAG), diode laser and surgical scalpel.A retrospective study has been made of 120 patients involving the removal of 128 epulis lesions with the CO2 laser, Er:YAG laser, diode laser and surgical scalpel. Postoperative controls were carried out after 7, 15 and 30 days to evaluate healing and wound evolution, and after 3, 6 and 12 months to assess possible relapse.Two groups were defined, based on the clinical and etiopathogenic characteristics of the excised lesions: gingival hyperplastic lesions (77 cases) and fibromatous hyperplasia (51 cases). The lower jaw was the most frequent location of gingival hyperplasia (51.9%). Fibrous hyperplasia was the most common histological diagnosis (49 cases; 63.6%). Percentage relapse following removal was 9.1%, of which 5 cases corresponded to fibrous hyperplasia. Only one malignancy was identified, corresponding to infiltrating squamous cell carcinoma. On the other hand, of the 51 treated cases of fibromatous hyperplasia, 58.8% were located in the upper jaw. These were histologically confirmed to be fibrous hyperplasia, with relapse in 19.6% of the cases.Although the different surgical techniques used for removal of epulis of the oral cavity are appropriate, we consider the CO2 laser to be the treatment of choice, since it offers a number of both intra- and postoperative advantages. On the other hand, all oral lesions require histological study to establish a firm diagnosis.

Juvenile hyaline fibromatosis (JHF) is an extremely rare, genetic disease with unknown etiology. It is characterized by cutaneous nodules and flexural joint contractures, along with hypertrophy of the gingival and oral mucosa, which is probably the most striking and morbidity-related feature of the disease. An advanced case of JHF with prominent growth retardation, recurrent respiratory tract infections, and impending upper respiratory tract obstruction due to severe hypertrophy of the oral mucosa and gingiva is presented. Surgical excision of the hypertrophic oral mucosa and cutaneous nodules in the scalp was performed. No major recurrence of the mucosal lesions was observed at the first postoperative year.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease of the connective tissue. It is characterized by papulonodular skin lesions, soft tissue masses, gingival hypertrophy, osteolytic bone lesions and flexion contractures of the large joints. Here, we report a 14-year-old girl with characteristic clinical features of JHF with early fatal outcome. Dermatopathologic examination of the early lesions however constantly lacked the so-called hyalin changes in multiple skin biopsies. According to our experience; dermatopathological features of this entity is not often and always consists of classical hyalinisation. Only larger lesions with long duration should expected to be exhibiting those features. Therefore we suggest that; JHF may often present itself as Juvenile Non-Hyaline Fibromatosis: JHF without prominent hyaline changes. And thus this fact should not change the actual diagnosis and prognostic implications.

Juvenile hyaline fibromatosis is an extremely rare inherited condition, probably resulting from an inborn error of metabolism. It is characterized by cutaneous nodules, gingival hypertrophy and joint contractions. It affects children but usually it is not present at birth, and is microscopically characterized by a conspicuous hyalinization of the connective tissue.

Gingival fibromatosis is a progressive gingival enlargement caused by an over growth of the collagenous element of the gingival fibrous connective tissue. Pharmacologically induced, hereditary (familial) and idiopathic forms of gingival fibromatosis are recognized. This paper reports a case of idiopathic gingival fibromatosis in a 13 year old boy involving the right maxillary and mandibular arches who had also been treated 3 years back for a gingival enlargement involving the left maxillary and mandibular arches. The enlargement was quite sever and caused significant esthetic and functional problems on both occasions.

The response of gingival fibroblasts cultured from humans with gingival fibromatosis to phenytoin (PHT) and nifedipine (NIF) was investigated. PHT and NIF induced proliferation, and increased the expression of immunoreactive endothelin-1 (ET-1). ET-1 (0.1 nm-1 microm) itself also induced proliferation in a concentration-dependent manner. The proliferation was inhibited by BQ-123 (ETA receptor antagonist; 1 microm) and TAK044 (ETA/ETB receptor antagonist; 1 microm), but not by BQ-788 (ETB receptor antagonist; 1 microm). The proliferation induced by PHT (0.25 microm) and NIF (0.25 microm) was inhibited by BQ-123 (1 microm). In addition, the results of Western blot analysis indicated the presence of ETA and ETB receptors in/on the fibroblasts. These findings suggest that PHT- and NIF-induced gingival proliferation may be mediated by endogenously generated ET-1, possibly via ETA receptors.

Hereditary gingival fibromatosis and sensorineural hearing loss in a 42-year-old man with Jones syndrome: Gingival fibromatosis is a rare disease, which can be seen as an isolated condition or associated with some uncommon syndromes. This case report describes the evaluation and treatment of a 42-year-old male patient with hereditary gingival fibromatosis, sensorineural hearing loss, undescended testis and maxillary odontogenic cyst (Jones Syndrome). Six years follow up of the index patient after the surgery revealed no recurrence of the gingival fibromatosis. This report also describes the anamnestic data of the patient's family that showed progressive deafness and gingival enlargement in three generations.

Hereditary gingival fibromatosis is a rare, genetically inherited overgrowth condition that is clinically characterized by a benign fibrous enlargement of maxillary and mandibular keratinized gingiva. A syndromic association between gingival fibromatosis and a wide variety of other genetically inherited disorders has been described. However, its coexistence with aggressive periodontitis has not been reported.A 24-year-old African-American female, patient (proband X, [Px]) reported with a chief complaint of tooth mobility and gingival enlargement. Clinical examination revealed moderate to severe gingival overgrowth on both mandible and maxilla. Generalized attachment loss and mobility of the teeth were observed. Radiographic evaluation demonstrated severe alveolar bone loss. The patient was diagnosed with gingival fibromatosis and aggressive periodontitis based on the clinical and radiographic findings. Her brother (Bx) and her mother (Mx) were evaluated and diagnosed with gingival fibromatosis suggesting that this is a dominant trait in the family and gingival fibromatosis might be of hereditary origin. In addition, the brother also exhibited localized aggressive periodontitis. Medical history revealed no other systemic or local contributory factors associated with the oral findings in any of the subjects.Surgical therapy included internal bevel gingivectomy combined with open flap debridement procedures for Px and Bx. Only internal bevel gingivectomy was performed for Mx since there was mild bone resorption and no intrabony defects. At the time of surgery, gingival biopsies were obtained and fixed in 4% paraformaldehyde. Multiple serial sections were stained with hematoxylin and eosin. Microscopic evaluation of the gingival specimens revealed large parallel collagen bundles associated with scarce fibroblasts in the connective tissue. The collagen bundles reached into the subepithelial connective tissue where elongated rete-pegs were also observed. Following the completion of the treatment, no signs of recurrence or bone resorption were observed over 2-year follow-up.This is the first report of hereditary gingival fibromatosis associated with aggressive periodontitis. Combined treatment comprising removal of fibrotic gingival tissue and traditional flap surgery for the elimination of intrabony defects represents a unique treatment approach in periodontal therapy. Two-year follow-up revealed that both the gingival overgrowth and the destructive lesions were successfully treated.

Oikarinen et al in 1989 reported a syndrome associated with generalized gingival fibromatosis and growth hormone deficiency. This is a case report of a 15-year-old female patient who presented to the Government Dental College, Chennai with generalized gingival fibromatosis and growth hormone deficiency. Interestingly, the histopathology of the excised gingival overgrowth showed dense collagenous connective tissue in which were strewn calcified structures that resembled cementum. This syndrome is being reported for the second time after its first case report in 1989 by Oikarinen et al. We are herewith reporting this case for its rarity with a brief review of literature of syndromes associated with generalized gingival fibromatosis.

Hereditary gingival fibromatosis (HGF) is a fibrotic gingival enlargement. In previous work, HGF fibroblasts grew faster and produced more collagen and fibronectin (FN) than normal gingival (GN) fibroblasts. HGF FN and collagen production, but not proliferation, were under autocrine transforming growth factor (TGF)-beta control, suggesting other means of activation of HGF proliferation. Elevated/prolonged expression of the proto-oncogene c-myc is implicated in disregulation of cell growth. The objectives of this study were to: 1) determine if c-myc expression is abnormal in quiescent and serum-stimulated HGF and GN fibroblasts and 2) determine the relationship between c-myc expression and fibroblast proliferation using a c-myc antisense oligonucleotide (ODN).Proliferation was determined by enzyme-linked immunosorbent assay (ELISA), measuring incorporation of bromodeoxyuridine into DNA. Expression of c-myc was determined by quantitative polymerase chain reaction (PCR), using incorporation of fluorescent dCTP and detection via electrophoresis.Proliferation was minimal until 24 hours or more after serum stimulation, when HGF proliferation was greater than GN (Por = 0.02). All cells expressed c-myc mRNA at quiescence andor = 1 hour after serum stimulation. Expression of c-myc in quiescent HGF fibroblasts was elevated, and it peaked and remained higher after serum stimulation than in GN cells. Proliferation of an HGF cell line was inhibited by 4 microM c-myc antisense ODN (14% decrease; Por = 0.006) and 8 microM c-myc antisense ODN (approximately 80% decrease; Por = 0.0001), but generally not by c-myc sense ODN. This effect was reversed by hybridizing the c-myc antisense and sense ODNs (P = 0.007).Data suggest that elevated proliferation of an HGF fibroblast cell line is related to elevated c-myc expression.

An unusual case of Zimmermann-Laband syndrome in a young male child with an unreported association of bilateral developmental cataract is presented. The pathognomonic triad of gingival fibromatosis, aplastic or hypoplastic distal phalanges with absent nails, and enlargement of soft tissues of the face were obvious, besides the known moderate learning disability and mild hearing loss. The case is discussed in the light of relevant literature. To the best of our knowledge, this is the first report of early developmental cataracts in association with the Zimmermann-Laband syndrome. Besides detection and timely recognition of the syndrome to allow adequate dental care, ophthalmic screening at periodic intervals is merited to improve the overall quality of life for these patients.

This report describes a rare case of hypoplastic primary incisor in which the pulp was exposed at the crown portion and covered by the gingiva in a 1-year-11-month-old boy. The patient was referred to us due to swelling of his labial cervical gingiva of the maxillary right primary central incisor, and on examination, extended to the hypoplastic labial surface. Radiographically, there was a round radiolucent area on the crown including the edge. Surgical removal of the swollen gingiva revealed a large defect of the labial aspect of the incisor, showing pulpal tissue inside. The tooth was treated by vital pulpotomy. Histopathologically, the removed gingival tissue contained many pieces of dysplastic tooth elements in the lamina propria portion which should have been connected to the exposed pulp. The findings suggested that pulp exposure resulted from focal dental hypoplasia not from resorption of the tooth.

Hereditary gingival fibromatosis (HGF) is a fibrotic enlargement of the gingiva. The mechanism that leads to the accumulation of abnormal amounts of gingival tissue in HGF is still unknown. The aim of this report was to present the clinical and histopathologic characteristics of a patient with gingival fibromatosis and to evaluate the proliferation of HGF fibroblasts.We examined the proliferation rate of fibroblasts in this case by using Ki-67 immunohistochemical staining and compared the rate to fibroblasts of non-fibromatosis gingival tissues from 5 healthy patients serving as controls.There were no Ki-67-positive cells in the lesional tissue, and the control gingiva revealed no immunostaining. The number of Ki-67 antigen-positive epithelial cell nuclei was observed to be low in the basal cell layers of hyperplastic gingival epithelia, similar to the control group.In the present case, there was no increase in the proliferation rate of lesional fibroblasts observed by Ki-67 immunohistochemical staining as a proliferation marker; only the epithelium was stained. It seems likely that the underlying mechanism of HGF may be an increase in the biosynthesis of collagen and glycosaminoglycans rather than cell proliferation.

Three cases of a relatively common but rarely reported intraoral condition are described. Clinically, this condition appears as an asymptomatic, tumor-like nodule or nodules along the labial anterior mucogingival line and are characterized histologically by an accumulation of dense collagenous tissue. This entity represents a developmental condition and should be distinguished from reactive and neoplastic lesions. No treatment is necessary.

There are many reasons for gingival hyperplasia. Mostly, proper oral hygiene is sufficient to achieve normal healthy gingiva. In some situations, however, gingival hyperplasia is drug-induced or can be a manifestation of a genetic disorder. In the latter, it may exist as an isolated abnormality or as part of a syndrome. If orthodontic treatment is needed in patients with gingival hyperplasia, both orthodontic and periodontal aspects need to be considered. Extreme hereditary gingival fibromatosis was periodontally treated, by removal of all gingival excess using flaps and gingivectomies. After a follow-up period, the orthodontic treatment started with fixed appliances. Monthly periodontal check-ups (scaling and polishing) were scheduled to control the gingival inflammation. After the orthodontic treatment, permanent retention was applied, once more followed by a complete gingivectomy in both maxilla and mandible. One of the most important keys to successful treatment of hyperplasia patients is the cooperation between the periodontist and the orthodontist.

Zimmermann-Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, abnormalities of the nose and/or ears, and absence or hypoplasia of nails or terminal phalanges of hands and feet. Other more variable features include hyperextensibility of joints, hepatosplenomegaly, mild hirsutism, and mental retardation. The genetic basis of ZLS is unknown; autosomal dominant inheritance has been suggested. We report an apparently balanced chromosomal aberration, 46,XX, t(3;8)(p13-p21.2;q24.1-q24.3), in a family with an affected mother and daughter. Using fluorescence in situ hybridization with BAC clones, we refined the breakpoints to 3p21.2 and 8q24.3 and, thereby, narrowed down both breakpoint regions to approximately 1.5 Mb. Our data provide additional support to the assumption that ZLS follows autosomal dominant inheritance. The 3;8 translocation described here represents a powerful resource to identify the causative gene for ZLS that maps most likely to one of the breakpoints.

Hereditary gingival fibromatosis is characterized by various degrees of attached gingival overgrowth. It usually develops as an isolated disorder but can be one feature of a syndrome. A case of a 38-year-old female is reported who presented a generalized severe gingival overgrowth, involving the maxillary and mandibular arches and covering almost all teeth. The clinical differential diagnosis included drug-induced overgrowth as well as idiopathic gingival fibromatosis.Excess gingival tissue was removed by conventional gingivectomy. As the gingival enlargement was generalized to all quadrants, on both sides, the surgery was carried out under general anaesthesia. The postoperative course was uneventful and the patient's appearance improved considerably. Post-surgical follow-up after 20 months demonstrated a slight recurrenceHereditary gingival fibromatosis is a rare disorder characterized by the proliferative fibrous overgrowth of the gingival tissue. Resective surgery of the excess tissue is the treatment available. However, recurrence is a common feature.

To ascertain histology changes of hereditary gingival fibromatosis (HGF) and the location of HGF gene.A 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.The 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.The gingival pathologic changes resemble "hamartoma"; the findings has implications for identification of the underlying genetic basis of HGF.

A case of a 9-year-old child with hereditary gingival fibromatosis, supernumerary tooth, chest deformities, auricular cartilage deformation, joint laxity and undescended testes is described. The exact mode of inheritance is unclear; a new mutation pattern is possible. These features resemble but differ from the previously reported Laband syndrome. The dental treatment consisted of surgical removal of the fibrous tissue and conservative restorative treatment under general anesthesia. The dental practitioner should be alert for developmental abnormalities such as supernumerary teeth and delayed tooth eruption. A comprehensive medical history and physical systemic evaluation is essential to rule out other systemic abnormalities. Genetic consultation is mandatory for future family planing.

Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxilla and mandible. In vitro, HGF fibroblasts demonstrate a proliferative index significantly higher than fibroblasts from normal gingiva (NG). The objective of this study was to determine the effect of dihydrotestosterone on the proliferation of gingival fibroblasts derived from patients with HGF (n = 4) and from four healthy individuals. Additionally, we analyzed the effect of dihydrotestosterone on interleukin-6 (IL-6) production and determined the expression levels of androgen receptors in NG and HGF fibroblasts. Gingival fibroblasts from NG and HGF were incubated with increasing concentrations of dihydrotestosterone with or without androgen blockers, and cultured for 24 h, and the proliferation index was determined by automated cell counter. IL-6 production, in this system, was quantified using a "capture" enzyme-linked immunosorbent assay (ELISA). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of androgen receptors. The results indicated that dihydrotestosterone simultaneously downregulates the production of IL-6 and upregulates the cell proliferation. Finasteride and cyprosterone acetate, two anti-androgens, partially reversed these effects. Androgen receptor mRNA expression was identified in both NG and HGF fibroblasts; however, the levels in NG were higher than those observed in HGF. These results show that testosterone coordinates the proliferation and production of IL-6 of normal and HGF fibroblasts.

This report addresses the complex nature of oral diagnosis, treatment and long-term case management in the hereditary form of recurrent gingival fibromatosis. Case management is discussed in relation to a 13-year-old girl who presented with recurrent, progressive gingival enlargement requiring consecutive periodontal and orthodontic treatment. The initial course of treatment included 4-quadrant gingivectomy with reverse bevel incisions, followed by orthodontics. Microscopic examination of the gingivectomy specimens supported the clinical diagnosis. Three years later, recurrence of the condition was observed in all quadrants. To facilitate orthodontic tooth movement and to achieve optimal esthetics, another full-mouth gingivectomy was performed. There was no recurrence of the condition a year later. It is recommended that patients with this condition be monitored closely after gingivectomy, so that the treatment requirements of localized areas can be addressed as needed.

Gingival fibromatosis is usually seen as an isolated finding or occasionally in association with other features as part of a syndrome. The combination of gingival enlargement, hypertrichosis, epilepsy and mental retardation is also a commonly reported syndrome that features gingival fibromatosis. The following report is about a mentally retarded patient who has shown no sign of hypertrichosis, but has been taking phenobarbital as a long-term therapy drug for anti-convulsion. Long-term management of this patient has been carried out from the age of one-and-a-half years to 14 years old. The patient's clinical features, treatment received, histopathologic presentation of gingival fibromatosis and proper management of the condition are discussed.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease with onset in infancy or early childhood. It is characterized by papulonodular skin lesions, soft tissue masses, gingival hypertrophy, and flexion contractures of the large joints. The light and electron microscopic features are very distinctive. Here we report an 8-month-old boy with characteristic stiffness of the knees and elbows and pink confluent papules on the paranasal folds, and periauricular and perianal regions. He also had hard nodules all over the scalp and around the mouth, and severe gingival hypertrophy. Histologic and ultrastructural features were typical of JHF. Clinical features, pathology, and physiology are discussed.

Objective To describe two patients with hereditary gingival fibromatosis (HGF) and growth hormone deficiency and to review the literature on HGF and related endocrine abnormalities. Methods We present case reports of two patients (first cousins)—an 8-year-old girl and a 13-year-old boy—with an existing diagnosis of HGF, who were assessed because of presumed growth failure. Both patients underwent growth hormone stimulation testing and more in-depth endocrine evaluation, including measurement of morning cortisol, adrenocorticotropic hormone (ACTH), and prolactin levels as well as thyroid function tests. An ACTH stimulation test was also performed. Radiologic evaluation included assessment of bone age and magnetic resonance imaging of the brain. Results In addition to HGF, both patients had short stature, subnormal growth velocity, and delayed bone age but no abnormalities on magnetic resonance imaging of the brain. Serum prolactin levels and results of thyroid function tests were normal. Subnormal growth hormone response was noted during hypoglycemia and pharmacologic stimuli with clonidine and levodopa. The female patient, who also had recurrent hypoglycemic episodes, had a suboptimal cortisol and ACTH response during hypoglycemia. On the ACTH stimulation test, she showed an inadequate cortisol response at 30 minutes but a normal response at 60 minutes. The male patient had normal morning cortisol and ACTH levels plus a normal response to ACTH stimulation. Both patients are responding well to treatment with growth hormone. The girl is also receiving cortisol replacement and has had no further episodes of hypoglycemia. Conclusion Although HGF has been described as an isolated finding, it can occur as part of a syndrome, including infrequent endocrine abnormalities such as growth hormone insufficiency. The cause of the growth hormone deficiency remains unclear in these two patients. We believe that patients with HGF should be monitored carefully for a prolonged period for growth as well as other endocrine abnormalities. (Endocr Pract. 2001;7:383- 387)

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disease. It is clinically a very variable disorder. Hamartomas can develop in many different organs, including the skin, kidneys, heart and brain. Diagnosis of patients with minimal expression of the disease can be very difficult. The dentist can contribute to the (early) diagnosis of the disease.

Drug therapy and hereditary factors are two of the main causes of gingival overgrowth (GO). Both of these forms of GO are associated with increased extracellular matrix production by fibroblasts. Transforming growth factor beta (TGF-beta) is an important mediator of wound healing and tissue regeneration, which stimulates fibroblasts to produce extracellular matrix materials. The aim of this immunohistochemical study was to determine whether there is any altered expression of TGF-beta isoforms or its receptors in tissue from patients with drug-induced GO (DIGO; n=10) and hereditary gingival fibromatosis (n=10) when compared to non-overgrowth tissue (n=10). Compared to control tissues, significantly more fibroblasts expressed TGF-beta1 in both DIGO and hereditary gingival fibromatosis tissues (P0.03). Cells expressing TGF-beta2 were present at control levels in DIGO but were significantly reduced in hereditary gingival fibromatosis (P0.02). By contrast, the number of TGF-beta3-positive cells was the same in overgrowth tissues and controls. However, because of differences in total fibroblast densities between groups, there was a proportional increase in TGF-beta3 as well as TGF-beta1 expressing cells within both overgrowth populations (P0.0001). Furthermore, representation of the TGF-beta2-positive phenotype was reduced in hereditary gingival fibromatosis (P0.01) but increased in DIGO (P0.005) compared to controls. Absorbance measurements of the positive cell populations showed that the level of expression was significantly higher for TGF-beta1 in hereditary gingival fibromatosis (P0.002) and significantly lower for TGF-beta3 in DIGO (P0.03). No significant differences in the numbers of TGF-betaRI- or RII-positive cells were detected between overgrowth tissues and controls. However, there were increases in the proportion of receptor-positive cells in the total cell population analysed in overgrowth tissues (P0.0001). These results indicate qualitative and quantitative differences in TGF-beta isoform and receptor expression by fibroblasts in gingival overgrowth that may contribute to disease pathogenesis.

Three cases of generalized and severe HGF in young patients of the same family without other features are reported. The purpose of this article is to present documented cases and discuss the identification, treatment, and control of the disease. The histopathological characteristics of HGF are emphasized.

In this paper, we describe two siblings with Juvenile Hyaline Fibromatosis (JHF) who were diagnosed at the age of 34 and 29 years respectively. JHF is a very congenital disease, mainly diagnosed in the first few years of life, with less than 40 published cases in literature. All the main clinical features of this syndrome, which may be summarised as multiple subcutaneous tumours, marked gingival hypertrophy, flexion contractures and osteolytic lesions were present in both of these cases. Clinical, radiological and histological differential diagnosis of JHF were made. Recent information about histopathology, treatment and prognosis of JHF was also reviewed.

Hereditary Gingival Fibromatosis (HGF) is the most common genetic form of gingival fibromatosis. The condition is most frequently reported to be transmitted as an autosomal-dominant trait, but autosomal-recessive inheritance has also been reported. The clinical presentation of HGF is variable, both in the distribution (number of teeth involved) and in the degree (severity) of expression. It is unknown if the variable clinical expression of HGF in different families is due to variable expression of a common gene mutation, allelic mutations, or non-allelic mutations. The apparently different modes of Mendelian inheritance of HGF suggest genetic heterogeneity. A gene locus for HGF has been localized to a 37-cM genetic interval on chromosome 2p21-p22 (D2S1352, Zmax = 5.10, θ = 0.00) flanked by D2S1788 and D2S441. To evaluate the generality of this linkage, we tested linkage with 9 markers from this candidate region in another large family, segregating for an autosomal-dominant form of generalized HGF, and found no support for linkage with any of these markers. Furthermore, statistical tests of this apparent heterogeneity were highly significant. Analysis of these data provides direct evidence that at least two genetically distinct loci are responsible for autosomal-dominant hereditary gingival fibromatosis.

Hereditary gingival fibromatosis (HGF, MIM 135300; approved gene symbol GINGF) is an oral disease characterized by enlargement of gingiva. Recently, a locus for autosomal dominant HGF has been mapped to an 11-cM region on chromosome 2p21. In the current investigation, we genotyped four Chinese HGF families using polymorphic microsatellite markers on 2p21. The HOMOG test provided evidence for genetic homogeneity, with evidence for linkage in four families (heterogeneity versus homogeneity test HOMOG, χ2 = 0.00). A cumulative maximum two-point lod score of 5.04 was produced with marker D2S390 at a recombination frequency of θ = 0 in the four linked families. Haplotype analysis localized the hereditary gingival fibromatosis locus within the region defined by D2S352 and D2S2163. This region overlaps by 3.8 cM with the previously reported HGF region. Single-strand conformation polymorphism and sequence analysis of the coding region of cytochrome P450 1B1 (CYP1B1) excluded it as a likely candidate gene.

Fibromatose gengival hereditária (FGH) é uma condição bucal rara clinicamente manifestada por um aumento gengival generalizado e fibrótico, podendo apresentar-se de forma isolada ou associada a outras alterações, como parte de síndromes. Os mecanismos biológicos envolvidos na FGH são desconhecidos, e os resultados de estudos de cultura celulares são controversos. Para elucidar as características fenotípicas dos fibroblastos de FGH, nós isolamos quatro linhagens celulares de fibroblastos de FGH de indivíduos de uma mesma família e comparamos as características morfológicas e proliferativas com fibroblastos provenientes de pacientes com gengiva clinicamente normal (GN). Fibroblastos de GN e FGH em condições de subconfluência celular apresentaram típicas características morfológicas, como formato fusiforme, núcleo central e longos prolongamentos citoplasmáticos, mas em condições de saturação da densidade celular, os fibroblastos de FGH apresentaram dimensões menores que as células controle. A relação núcleo/citoplasma foi sempre menor para todas as linhagens celulares de fibroblastos de FGH, sugerindo que a redução celular, é proveniente de uma redução ou compactação citoplasmática e não nuclear. A capacidade proliferativa de fibroblastos de FGH foi maior que a de fibroblastos de GN. Estes resultados sugerem que diferenças morfológicas e proliferativas dos fibroblastos de FGH podem estar associadas aos eventos biológicos envolvidos na etiopatogenia do aumento gengival observado em pacientes com FGH. Hereditary gingival fibromatosis (HGF) is a rare oral condition, clinically manifested through a generalized and fibrotic enlargement of the gingiva, which may present as an isolated clinical finding or in association with other features, as part of a syndrome. The biological mechanisms involved in HGF are unknown, and the results of cell-culture studies are controversial. To elucidate the phenotypic and proliferative characteristics of HGF fibroblasts, we isolated 4 cell lines of gingival fibroblasts from members of the same family with HGF, and compared with gingival fibroblasts from 4 healthy patients (NG). HGF and NG fibroblasts, in subconfluent culture densities, showed typical morphological characteristics, such as spindle form with a central spherical nucleus and long cytoplasmatic prolongations, but in saturation density, HGF cells were shorter than control cells. The nucleus/cytoplasm relation was always smaller in all HGF cell lines, suggesting that the cellular reduction is derived from reduction or compaction of the cytoplasm and not of the nucleus. The proliferation rate was higher in fibroblasts from HGF than in the ones from NG. These results suggest that differences in the morphology and proliferation of HGF fibroblasts may be associated with the biological events involved in the pathogenesis of gingival overgrowth in HGF patients.

Hereditary gingival fibromatosis is frequently an isolated condition of little consequence apart from a cosmetic problem and occasional associations with hypertrichosis and/or epilepsy. There are, however, several uncommon or rare eponymous syndromes described in which gingival fibromatosis can be a feature: these include the Zimmermann-Laband, Murray-Puretic-Drescher, Rutherfurd, Cowden and Cross syndromes. This paper describes two siblings with features of the rare Zimmermann-Laband syndrome and discusses the major aspects of this and other eponymous syndromes that may be associated with hereditary gingival fibromatosis.

Gingival fibromatosis (GF) occurs in several genetic forms as a simple Mendelian trait, in malformation syndromes, and in some chromosomal disorders. Specific genes responsible for GF have not been identified. An autosomal dominant form of hereditary gingival fibromatosis (HGF, MIM 135300) was recently mapped to chromosome 2p21 in a large Brazilian family and there was an earlier report of GF in a boy with a cytogenetic duplication involving 2p13→p21. We thus hypothesised that a common gene locus may be responsible for GF in both the Brazilian family and the boy with the chromosome 2p duplication. We performed additional genetic linkage studies on the Brazilian family and molecular cytogenetic studies on the patient with the cytogenetic duplication to correlate more precisely the genetic interval of the HGF phenotype with the duplicated 2p interval. Additional linkage analysis of new family members resulted in refinement of the candidate region for HGF to an 8 Mb region. Molecular cytogenetic analysis of the 2p13→p21 duplication associated with GF showed that the duplicated region was proximal to the candidate interval for HGF. Thus, our results support the presence of two different gene loci on chromosome 2p that are involved in GF. Keywords: gingival fibromatosis; chromosome duplication; chromosome 2

Gingival fibromatosis is frequently an isolated condition, but rarely associated with some uncommon syndromes. This paper describes an 11-year-old patient with pronounced gingival enlargement, cherubic facial appearance, and psychomotor retardation and discusses the major aspects of the case. The most striking finding orally was the presence of grossly hyperplastic gingiva, which completely covered all teeth except the occlusal surfaces of some teeth. The swelling in the lower part of the face and the appearance of sclera beneath the iris suggest cherubism. The diagnosis was confirmed by the detection of giant cell regenerative granuloma and perivascular eosinophilic particles and osteoclasts after biopsy of the mandible. In this case, surgery was the only effective way to treat the patient. A full-mouth gingivectomy procedure was performed under general anesthesia in 2 stages. The case was followed for 12 months and no recurrence was seen. An appropriate oral hygiene regimen was established.

Hereditary gingival fibromatosis (HGF) is an oral condition characterized by the enlargement of the gingiva of both the maxilla and mandible. To study the cell proliferation index of fibroblasts from HGF and normal gingiva (NG), cell cultures from 4 members of the same family with HGF and from 4 healthy patients were established. Our results obtained from 6 different cell proliferation assays clearly showed that the cell proliferation rate was significantly higher in fibroblasts from HGF than from normal gingiva. HGF and control fibroblasts in subconfluent culture densities were typically spindle, but in saturation density HGF cells were shorter than control cells. These data suggest that the higher proliferative index of HGF fibroblasts possibly has a role in the pathogenesis of gingival outgrowth in HGF patients.

A case of Laband syndrome in an 8-yr-old girl is presented. The case is sporadic. The patient manifests enlargement of the soft tissue of the hard palate and the gingiva, which partly or completely covers the crowns of the teeth and macroglossia. The cartilagenous part of the nose and the ears is large and soft. She has synophrys and thick, straight hair. The nails of the fingures and toes are dysplastic. The girl exhibits no other abnormality, except an IQ of 61.

Juvenile hyaline fibromatosis is a rare autosomal recessive interstitial disease characterized by nodes and tumours of skin and soft tissues as well as by gingival hyperplasia. The authors described a case of 28-year-old male based on histopathological diagnosis. The patient was admitted to the hospital thrice in his life with the diagnosis of arthrogryphosis. Last time he presented with extensive secondary impetigo in extremities and pachydermia, polymalformation syndrome, multiple subcutaneous tumours, gingival hypertrophy, contractures, osteolytic lesions and positive family history. In histology, tumoriform lesions showed a structureless hyaline matrix often with chondroosseous metaplasia and calcium salts. More or less numerous cells in the matrix had a fibroblastoid appearance with eosinophilic cytoplasm, oval nuclei and frequently pericytoplasmic halo. Electron microscopy revealed dilated cisterns of rough endoplasmic reticulum and a hypertrophied Golgi apparatus. Particles representing calcium salts according to their density were rare. Immunohistochemistry of tumour cells showed vimentin, alpha-1-antichymotrypsin and alpha-1-antitrypsin. The findings concurred with the literature in which, nevertheless, the immunohistochemical picture were not mentioned.

Juvenile hyaline fibromatosis (JHF) is rare disease of autosomal recessive inheritance.A 14-year old boy, born to consanguineous parents was admitted because he suffered from multiple tumors since the age of 5 years. These tumors were mobile, painful varying in size, located mainly on the head, the back, and extremities; they were associated with gingival overgrowth. Bone X-rays showed osteolytic lesions. The cognitive development was normal. Biopsy of tumors showed cords of spindle-shaped cells embedded in homogeneous eosinophilic matrix. The child was progressively disabled due to articular changes. Two of his brothers presented the same features.This new case of JHF confirms the severity of prognosis of such a fibromatosis presently considered as a hereditary disorder of collagen metabolism.

Human gingival fibroblasts derived from tissue explants of two patients with dilantin-induced gingival hyperplasia (DGH) and one patient with idiopathic gingival fibromatosis (GF) were studied with respect to the effect of epidermal growth factor (EGF) on the proliferative characteristics of these cells. Immunohistochemical staining showed that there were more EGF receptor-positive cells among DGH fibroblasts than among either normal gingival fibroblasts (NG) or GF cells. Furthermore, EGF binding studies showed that, in spite of there being no disparity in binding affinity among all these cells, DGH fibroblasts possessed approximately two-fold more EGF receptors than either NG or GF cells. In addition, the growth-promoting effect of exogenously added EGF was concentration-dependent in DGH fibroblasts but was not in either NG or GF cells. All of the above findings clearly demonstrate that DGH and GF fibroblasts exhibit distinct disparity in proliferative responsiveness to EGF and suggest that different mechanisms may be involved in the pathogenesis of these two forms of gingival hyperplasia. These observations also suggest a possible therapeutic approach for blocking EGF-induced cell proliferation in DGH.