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The diagnosis and treatment of gingival enlargement has raised many questions among clinicians and researchers for many years. Recently, the term "enlargement" was recommended in lieu of hyperplasia or overgrowth to define a broader clinical finding and to differentiate specific pathologic lesions from common signs of inflammatory changes at tissue level (eg, edema and hypervascularization).1 Gingival enlargement is defined as an overgrowth or increase in the size of the gingiva, is a common feature in gingival diseases, and may be caused by a variety of factors.2 Inflammation, medications, systemic diseases, and neoplastic tissue changes all can be classified as the etiologic features.
Based on the American Academy of Periodontology (AAP) 1999 Classification of Periodontal Diseases and Conditions, gingival enlargement can occur because of pregnancy-associated hormonal changes, various medications causing changes in extracellular matrix physiology, or genetic disorders. 3,4 Independent from inflammatory etiological factors, periodontal tumors and cysts also may present as localized gingival enlargements.1 The tissue enlargement may be localized or generalized, confined to the marginal gingiva or to the papillary tissue, and involve both the marginal and attached gingivae. 5 The degree of enlargement can be categorized as follows6:
- Grade 0: No gingival enlargement.
- Grade 1: Enlargement confined to interdental papilla.
- Grade 2: Enlargement involving papilla and marginal gingivae.
- Grade 3: Enlargement covering three quarters or more of the crown.
Hereditary gingival fibromatosis (HGF), also referred to as idiopathic gingival hyperplasia, is one type of gingival enlargement. It is a rare disease of the gingiva characterized by firm, enlarged gingival tissue that covers most of the anatomic tooth crowns.7 The onset of the disease is common during the eruption of the permanent incisors,7 but several reports also have mentioned involvement of the deciduous dentition.8-11 It is classified as a non-plaque-induced gingival lesion caused by various genetic disorders.1
HGF may occur as an isolated disorder, but it also has been reported to be associated with various syndromes and other abnormalities.12 Case reports have associated HGF with Zimmerman-Laband syndrome (ear, nose, bone, and nail defects), Murray-Puretic-Drescher syndrome (juvenile hyaline fibromatosis), Cowden syndrome (multiple hamartoma), Cross syndrome (microphthalmia, mental retardation, athetosis, hypopigmentation), Rutherford syndrome (corneal dystrophy), and Prune belly syndrome (absence of 1 or more layers of abdominal muscles). 13,14 In addition, there may be a relationship between a deficiency in growth-related hormones and gingival enlargement.6 Features found in association with HGF include mental retardation, epilepsy, progressive sensorineural hearing loss, and abnormalities of the toes and fingers, but hypertrichosis is the ancillary abnormality most commonly seen.6
This review focuses on the clinical differentiation of HGF from other types of gingival enlargements and on known regulatory mechanisms that may be important in the treatment outcome and control of the disease occurrence.
This review focuses on the clinical differentiation of HGF from other types of gingival enlargements and on known regulatory mechanisms that may be important in the treatment outcome and control of the disease occurrence.8
Clinical Presentation
HGF features an asymptomatic, nonhemorrhagic, nonexudative, and proliferative lesion of the gingival tissue. 13 Gingival tissue is generally pink and stippled, but itmay become red with superimposed inflammation because of plaque accumulation. The tissue is fibrotic and displays a nodular or minutely pebbled surface.15 Often an exaggerated stippling is present.16 The tissue can become so firm and fibrous that it feels like bone on palpation.17 This is in contrast to many other presentations of gingival enlargement (eg, those that are drug induced) where the tissue is somewhat moveable.18 Both free and attached gingival tissue are affected, but the enlargement does not extend beyond the mucogingival junction (Figures 1 and Figure 2)17
Two different types of HGF have been classified based on HGF clinical presentations. The nodular form is characterized by multiple focal enlargements in the dental papillae, and the symmetric form results in a more uniform enlargement of the gingival tissue. These clinical modalities can occur in conjunction with each other or as isolated lesions. The symmetric form is more common, and the maxilla and mandible are equally affected (Figures 1 and Figure 2).13,17 The localized form is generally seen in the maxillary tuberosity and molar area, predominately on the palatal aspect.17
HGF gingival enlargement can cover the coronal portion of a tooth, up to its occlusal surface. This overgrowth also may extend to the palate, which alters its contour. The resultant effect may include speech difficulty and painful mastication as food deflects onto the enlarged tissue. In severe cases, the jaws appear bulbous.15 Other common side effects are diastema, malocclusion, and prolonged retention of primary teeth.13 Perhaps most importantly, the enlarged tissue creates retention for plaque. Although Emerson reported no significant association between oral hygiene (the amount of calculus present) and the degree of enlargement, the inability to remove plaque from the teeth is well known to contribute to dental caries, the development of gingivitis, and periodontitis in individuals affected with HGF.18
Etiology and Histopathology of HGF
Evidence for Hereditary Involvement
HGF is inherited in both autosomal dominant and recessive modes. It is reported to have a phenotype frequency of 1:175,000 and a gene frequency of 1:350,000, assuming that the condition to be inherited is the result of an autosomal dominant gene.19 In a study by Rushton, 54 of the 109 total cases were the offspring of marriages of affected and unaffected persons.20 Weski documented 5 generations and 9 marriages between affected and unaffected subjects and reported that of the 38 offspring, 9 women and 5 men were affected.21 Barros and colleagues also reported that 50 of 96 affected persons were consistent with an autosomal dominant mode of inheritance with complete penetrance.22 Several reports of recessive transmission of the disorder also exist in the literature.10,23,24
Recently, researchers have identified 3 genetically separate loci.25-27 These loci are on chromosome 2p21- p22 (GINGF), 2p22.3-23.3 (GINGF3), and 5q13-q22 (GINGF2). Hart and colleagues identified a mutation in the Son of sevenless-1 (SOS1) gene, which results in a single nucleotide insertion mutation in codon 1083 of GINGF.28 This mutation appears as autosomal dominant. The exact method of transmission of expression for the recessive form of HGF is still being studied.
Histopathology
HGF causes enlargement of the attached gingival tissue because of an increase in the amount of connective tissue. This fibrosis is characterized by densely arranged collagen bundles, numerous fibroblasts, and connective tissue that is relatively avascular.29,30 Thickened and acanthotic epithelium also is present with elongated rete pegs (Figure 3).5 Small calcified particles, islands of osseous metaplasia, ulceration of the overlying mucosa, and inflammation can be occasionally observed.30
Barros and colleagues found that the organization of the collagen fibers in connective tissue obtained from HGF lesions carried fibrils with an irregular outline, sometimes in loops, interspersed throughout normal fibrils. 22 This was attributed to the increased number of matrix substances and filaments in a branching network. They also observed that oxytalan fibers were common, but the number of elastic fibers was diminished. Similar degenerative changes of elastic fibers, coupled with the increase of fine fibrils, interspersed among defective collagen fibrils have been commonly reported in diseases in which there are close pathogenic relationships between elastic fiber alteration and collagen fiber alteration.31
Two morphologically different fibroblast types exist in HGF gingiva.29 One phenotype exhibits relatively little cytoplasm and is considered inactive, and the other phenotype has fully developed Golgi apparatus and rough endoplasmic reticulum, suggesting a highly active phenotype. 29,32,33 The concurrent development of HGF with tooth eruption suggests that a particular cell selection or activation of certain fibroblast clones by physical trauma or mononuclear cell products may participate in HGF pathogenesis.20,34 Thus, the HGF fibroblasts appear to be phenotypically activated during tooth development.
There are controversial reports on fibroblast growth rate and the amount of collagen production by fibroblasts isolated from gingiva of HGF patients. Johnson and colleagues and Shirasuma and colleagues reported that HGF fibroblasts grew more slowly than or equal to normal gingival fibroblast growth,32,34 but a more recent study by Tipton and colleagues found HGF fibroblasts to have an increased proliferative rate.35 Similarly, there is a disagreement regarding the amount of collagen production. According to Tipton and colleagues, HGF fibroblasts produce up to twice the amount of type I collagen as normal fibroblasts, which contributes to the enlargement and fibrosis of the gingiva.35 In contrast, Johnson and colleagues reported that HGF fibroblasts synthesized 50% of the amount of collagen than what is released from the normal gingival fibroblasts.32 These disparities appear to rest on the poorly understood role of the heterogeneous phenotypic expression of the fibroblast.
The possible disturbance in the homeostatic equilibrium between synthesis and degradation of extracellular matrix molecules also has been recently studied.36 Matrix metalloproteinases (MMPs) are a family of enzymes involved in degrading various components of the extracellular matrix. It has been reported that MMP- 1 and MMP-2 expression and production are lower in fibroblasts from HGF patients.37 It has been postulated that enhanced transforming growth factor-beta 1 (TGF- b1) and interleukin-6 (IL-6) production increases the synthesis and reduces the proteolytic activities of fibroblasts from patients with HGF, which may favor observed accumulation of the extracellular matrix.36,37
Treatment
Historically, clinicians have reported several approaches to alleviate gingival enlargement. Treatment modalities have ranged from conservative and surgical procedures to extraction of all teeth and reduction of the alveolar bone to prevent recurrence.24,38 Most of these reports discuss a necessity for repeated surgical excision of the tissue to restore the gingival contours because of the high recurrence of the condition.7 Factors to consider in treatment planning include esthetic and functional needs, as well as the onset of puberty because recurrence is predominately observed in children and teenagers rather than in adults.8 In addition, active orthodontic treatment may play a role in inducing gingival enlargement in these patients.14
Currently available surgical methods for the excision of large quantities of tissue include conventional gingivectomy with a scalpel, electrocautery, and laser surgery (Figure 4). Restoration of physiological contours of the gingiva and maintaining good postoperative care to minimize recurrence are important for a successful treatment outcome.18 Some reports suggested that laser use is more advantageous than alternative surgical protocol because it has the ability to coagulate and seal blood vessels, vaporize the tissue, make accurate incisions, and improve healing because of its antimicrobial properties.39 However, there are not enough scientific evidence and clinical findings to prove these advantages.40
There is disagreement among clinical reports for the timing of surgical treatment, how many surgeries should be performed, and how far apart the treatments should be. Nevertheless, postoperative care protocol generally includes chlorhexidine mouthrinse and periodontal dressing with or without hemostatic reagents. Recurrence of the lesion, in which the gingiva returns to the original state, may occur within 1 to 2 years depending on the initiation age of the HGF symptoms (Figure 5).23,38
Conclusion
Although there are similarities in the clinical presentation, recent studies reveal that etiology and pathogenesis of HGF are distinct from other types of gingival enlargements. Treatment planning, the actual treatment, and evaluation of the treatment outcome should include various modalities. This review gives an update on recent investigations and the clinical relevance of this information.
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About the Authors
Samuel DeAngelo, DDS, MS
Private Practice
Apex, North Carolina
James Murphy, DDS, MS
Clinical Assistant Professor
Section of Periodontology
Lewis Claman, DDS, MS
Associate Professor
Director of Predoctoral Periodontology Program
John Kalmar, DMD, PhD
Clinical Associate Professor
Graduate Program Director of the Oral and Maxillofacial Pathology
Binnaz Leblebicioglu, DDS, MS, PhD
Assistant Professor
Section of Periodontology
The Ohio State University, College of Dentistry
Columbus, Ohio