Clinical presentation and management of hereditary gingival fibromatosis: Four case reports

Abstract

BACKGROUND

Hereditary gingival fibromatosis (HGF) is a rare disorder characterized by progressive gingival enlargement. We report two patients with non-syndromic HGF and two with syndromic HGF, detailing their clinical characteristics, diagnosis, multidisciplinary management, and long-term follow-up.

CASE SUMMARY

All patients presented with generalized gingival enlargement. Patient 1 (5 years old), patient 2 (26 years old) and patient 3 (25 years old) had positive family histories. Patient 3 also exhibited generalized hypertrichosis and macromastia, whereas patient 4 (11 years old) presented with facial hypertrichosis and clitoral hypertrophy. Patient 1 and patient 4 underwent gingivectomy and gingivoplasty under general anesthesia. Patient 2, who also had periodontitis, received initial periodontal therapy (oral hygiene instruction, scaling, and root planing) followed by periodontal surgery (gingivectomy and flap surgery). Patient 3 underwent a multidisciplinary approach that included tooth extraction, gingivectomy and gingivoplasty, dental implant placement, and orthodontic treatment. In all cases, gingival overgrowth was effectively managed and controlled.

CONCLUSION

Gingival hyperplasia in HGF demonstrates phenotypic variability. Diagnosis, whether non-syndromic or syndromic, relies on detailed clinical examination and family history. HGF can cause substantial aesthetic, functional, and psychological concerns; therefore, early intervention, multidisciplinary treatment, and long-term follow-up are crucial for optimal outcomes.

Key Words: Gingival hyperplasia; Hereditary gingival fibromatosis; Syndromes; Treatment; Case report

Core Tip: Periodontal surgery is effective for managing hereditary gingival fibromatosis (HGF) by exposing unerupted teeth and establishing an appropriate gingival contour. Early intervention, multidisciplinary treatment programs, and long-term follow-up are essential for achieving optimal outcomes in HGF.

INTRODUCTION

Hereditary gingival fibromatosis (HGF) is a rare, benign, and slowly progressive disorder characterized by fibrous enlargement of the free and attached gingiva and was first reported by Goddard[1] and Strzelec et al[2]. The prevalence is estimated at 1:175000 based on phenotype and 1:350000 based on genotype, with equal distribution between sexes. HGF commonly presents as an isolated condition [non-syndromic HGF, non-syndromic HGF (nsHGF)] or as part of a syndrome [syndromic HGF, syndromic HGF (sHGF)], including Cowden syndrome, Zimmermann-Laband syndrome, Cross syndrome, Rutherford syndrome, Ramon syndrome, Jones syndrome, Costello syndrome, and hyaline fibromatosis syndrome, among others[3,4]. The condition is often inherited in an autosomal dominant or recessive manner, and mutations in genes such as SOS1, REST and ZNF862 have recently been implicated in its pathogenesis[5-7]. Gingival enlargement can result in aesthetic, functional, and psychological challenges, including difficulties with speech, mastication, and occlusion, as well as altered facial features. In severe cases, HGF can delay or impede tooth eruption[8,9]. Here, we report four cases of HGF, including two nsHGF cases and two sHGF cases, all of which were treated and followed longitudinally. We discuss their clinical presentations, diagnostic pathways, multidisciplinary management, and long-term outcomes.

CASE PRESENTATION

Chief complaints

Case 1: A 5-year-old Chinese girl presented with her parents with a chief complaint of progressive, painless, full-mouth gingival enlargement for 3 years.

Case 2: A 26-year-old Chinese male presented with generalized gingival hyperplasia since age 6-7 years.

Case 3: A 25-year-old Chinese female reported chewing difficulty due to progressive gingival overgrowth for more than 20 years.

Case 4: An 11-year-old Chinese girl presented with her mother with a chief complaint of full-mouth gingival hyperplasia for 9 years.

History of present illness

Case 1: Gingival hyperplasia began with the eruption of the primary dentition and progressed rapidly, covering most teeth, resulting in aesthetic concerns and distress related to teasing by classmates.

Case 2: The patient reported slowly progressive, painless gingival enlargement since childhood. The gingiva was occasionally red, swollen, and bled during brushing. He reported no prior periodontal treatment.

Case 3: Progressive gingival hyperplasia over more than 20 years resulted in near-complete coverage of the mandibular teeth, markedly affecting appearance. She reported no history of periodontal treatment.

Case 4: Gingival enlargement since early childhood delayed eruption of the permanent dentition and contributed to dental crowding.

History of past illness

Cases 1 and 2: No significant past medical history was reported.

Case 3: The patient had generalized hypertrichosis affecting the face, limbs, and back, requiring regular hair removal. At age 15, she underwent bilateral breast reduction surgery for macromastia.

Case 4: The patient had clitoral hypertrophy since birth, but chromosome analysis results were normal.

Personal and family history

Case 1: The patient’s mother (30 years of age) had a history of similar generalized gingival hyperplasia (Figure 1A).

Figure 1 Family pedigrees of patients with hereditary gingival fibromatosis (patient 1, 2, and 3). A: Patient 1 and her mother presented with similar generalized gingival hyperplasia (arrow); B: Patient 2: More than ten family members exhibited similar characteristics (arrow); C: Family members of patient 3, including her mother, grandfather, grandfather’s sister, and cousin, showed generalized gingival hyperplasia (arrow).

Case 2: Family history findings indicated more than 10 affected members across three generations, consistent with an autosomal dominant inheritance pattern (Figure 1B). Genetic testing identified a novel heterozygous missense mutation (c.2812G>A) in the ZNF862 gene[7].

Case 3: Family history findings demonstrated affected members across three generations with a similar triad of gingival hyperplasia, congenital hypertrichosis, and, in females, macromastia (Figure 1C).

Case 4: The patient had no significant family history of gingival enlargement or related syndromes.

Physical examination

Case 1: Severe, generalized, fibrotic gingival enlargement with a pink color was observed, covering almost the entire clinical crown of the deciduous dentition (Figure 2A).

Figure 2 Intraoral photographs of patient 1. A: Initial visit showing severe generalized gingival enlargement covering almost the entire deciduous dentition; B: Follow-up at 6 months after periodontal surgery, with primary dentition exposed.

Case 2: Oral hygiene was poor, with generalized plaque and calculus accumulation. The gingiva was dark red, edematous, and hyperplastic, particularly in the maxillary posterior region (Figure 3A). Periodontal probing revealed generalized bleeding on probing (BOP), clinical attachment loss (CAL), and probing depths (PD) of up to 9 mm (Figure 4A).

Figure 3 Intraoral photographs of patient 2. A: Initial visit showing poor oral hygiene with obvious supra- and subgingival calculus; the gingiva was slightly red and swollen, and hyperplastic gingiva covered approximately one-third of the clinical crowns; B: Three-year follow-up after periodontal surgery showing significant exposure of clinical crowns without recurrence of gingival enlargement.

Figure 4 Periodontal examination of patient 2. A: Initial periodontal examination revealing periodontal pockets and inflammation (red font indicates bleeding on probing); B: Periodontal examination at 3-year follow-up after periodontal surgery showing significant improvement in all periodontal parameters. B-REC: Buccal recession; B-PD: Buccal probing depth; P-PD: Palatal probing depth; P-REC: Palatal recession; L-REC: Lingual recession; L-PD: Lingual probing depth.

Case 3: Extraoral examination revealed bimaxillary protrusion, a gummy smile, and oligodontia. Intraorally, severe gingival overgrowth covered more than two-thirds of the clinical crowns. Tooth # 46 was in linguoversion and exhibited grade II mobility, a furcation lesion, and nonvital status. Occlusion was neutral, with a class III underbite and increased overjet (Figure 5A). Generalized hypertrichosis was noted on the face, trunk, and limbs.

Figure 5 Intraoral photographs of patient 3. A: Initial visit showing poor oral hygiene, sparse dentition, and gingival overgrowth covering more than half of the clinical crowns; tooth # 46 was in linguoversion, and occlusal assessment revealed a neutral relationship with class III underbite and increased overjet; B: Follow-up at 3 months after periodontal surgery, with reestablished gingival contours and exposed dental crowns; C: Follow-up at 2 years after orthodontic treatment showing improved occlusal relationship without recurrence of gingival hyperplasia.

Case 4: Intraoral examination revealed severe gingival overgrowth covering more than two-thirds of the crowns, most prominently in the maxillary anterior region. Several deciduous teeth (# 53-55, 63-65, 74, 75, 84, 85) were retained, and eruption of the permanent dentition was delayed (Figure 6A). The patient also had facial hypertrichosis.

Figure 6 Intraoral photographs of patient 4. A: Initial visit showing severe gingival hyperplasia covering most of the clinical crowns, with multiple caries in the mixed dentition; B: Follow-up at 1 month after periodontal surgery.

Laboratory examinations

Complete blood count, coagulation profile, and liver and renal function tests results were within normal limits for all patients.

Imaging examinations

Case 1: Orthopantomogram (OPG) showed complete primary dentition with all permanent tooth buds present and no alveolar bone loss (Figure 7A).

Figure 7 Imaging findings. A: Orthopantomogram (OPG) of patient 1 showing all permanent tooth buds present without alveolar bone loss; B: OPG of patient 2 showing extensive alveolar bone resorption, particularly in the maxillary anterior region; C: OPG and cone-beam computed tomography of patient 3 showing # 46 in linguoclination with severe alveolar bone resorption; D: OPG of patient 4 showing mixed dentition without alveolar bone loss; permanent teeth # 12-22, 32-42, 16, 26, 36, and 46 had erupted, while deciduous teeth # 53-55, 63-65, 74, 75, 84 and 85 were still present; E: OPG of patient 2 at 3-year follow-up after periodontal surgery showing no further alveolar bone loss.

Case 2: OPG revealed generalized alveolar bone loss, most pronounced in the anterior region (Figure 7B).

Case 3: OPG and cone-beam computed tomography showed no significant bone loss except for tooth # 46, which exhibited severe alveolar bone loss and furcation involvement (Figure 7C).

Case 4: OPG revealed a mixed dentition without alveolar bone loss. Several permanent teeth (# 12-22, 32-42, 16, 26, 36, and 46) had erupted, whereas multiple deciduous teeth (# 53-55, 63-65, 74, 75, 84, and 85) were retained (Figure 7D).

FINAL DIAGNOSIS

Case 1

Based on family history and clinical findings, the patient was diagnosed with nsHGF. The diagnosis was subsequently confirmed by histopathological examination of gingival tissue obtained during periodontal surgery, which revealed epithelium hyperplasia with elongated rete ridges extending into the underlying connective tissue. The connective tissue consisted of thick collagen fiber bundles with relatively few fibroblasts and blood vessels.

Case 2

Based on family history and clinical and radiographic findings, the patient was diagnosed with nsHGF and generalized periodontitis (stage III, grade B)[10]. The diagnosis was confirmed by genetic testing, which identified a novel ZNF862 mutation[8]. Histopathological examination of the excised gingival lesions was consistent with HGF.

Case 3

Based on family history and clinical findings, the patient was diagnosed with sHGF, presenting with the triad of gingival fibromatosis, congenital hypertrichosis, and macromastia. This rare syndromic combination has been reported only sporadically in the literature[11]. Additional diagnoses included chronic gingivitis, a periodontal-endodontic lesion at tooth # 46, and malocclusion. Whole-exome sequencing (WES) was performed on family members; however, the analysis revealed no mutations in known HGF-related genes, suggesting a novel pathogenic mutation. Histopathological findings of the gingival lesions were consistent with HGF.

Case 4

Based on clinical findings, the patient was diagnosed with sHGF, Zimmermann-Laband syndrome was initially suspected due to the presence of gingival enlargement, hypertrichosis, and clitoral hypertrophy[12]. However, WES did not identify any pathogenic mutations in genes associated with known syndromes. Further orthopedic consultation was recommended. Histological features of the excised gingival tissue were consistent with the diagnosis of HGF.

TREATMENT

Case 1

Due to functional impairment in mastication and speech, the patient underwent gingivectomy and gingivoplasty under general anesthesia to expose the teeth and establish a normal gingival contour.

Case 2

Initial therapy included oral hygiene instruction, scaling, and root planing. Due to persistent gingival enlargement and inflammation, quadrant-wise periodontal surgery (gingivectomy and flap surgery) was performed under local anesthesia. Supportive periodontal therapy was provided every 6 months.

Case 3

A multidisciplinary approach was implemented, including: (1) Extraction of hopeless tooth # 46; (2) Initial periodontal therapy; (3) Periodontal flap surgery, gingivectomy, and gingivoplasty under local anesthesia; (4) Dental implant placement in the #46 region; (5) Orthodontic treatment; and (6) Periodontal maintenance.

Case 4

A multidisciplinary approach was recommended, including: (1) Initial periodontal therapy; (2) Periodontal surgery, including flap surgery, gingivectomy, and gingivoplasty; (3) Extraction of teeth # 53, 54, 63, 64, 74, 84, and 85; (4) Restorative treatment for teeth # 55, 65, 75, and 24; and (5) Orthodontic treatment. However, patient 4 ultimately received only initial periodontal therapy followed by periodontal surgery under general anesthesia.

OUTCOME AND FOLLOW-UP

Case 1

At the 1-month and 6-month postoperative follow-up visits, favorable outcomes were observed, with successful exposure of the teeth. The patient and her parents reported high satisfaction. The patient remains on regular follow-up every 6 months (Figure 2B).

Case 2

Gingival enlargement was substantially reduced, with no recurrence at the 3-year follow-up (Figure 3B). Periodontal parameters (PD, CAL, BOP) were markedly improved (Figure 4B), and OPG showed no further bone loss (Figure 7E).

Case 3

Three months after periodontal surgery, gingival contours were reestablished (Figure 5B). Two years after completion of orthodontic treatment, gingival enlargement had resolved, and the facial profile and occlusion were markedly improved (Figure 5C).

Case 4

At the 1-month follow-up visit, significant improvement was observed, with successfully exposure of the crowns (Figure 6B). However, the patient was subsequently lost to follow-up.

DISCUSSION

Gingival enlargement, also known as gingival overgrowth, is a common clinical finding characterized by increased gingival volume[13]. However, the wide variability in clinical presentation can make a definitive diagnosis challenging. The differential diagnosis of generalized gingival hyperplasia is broad and includes inflammatory enlargement, drug-induced enlargement, enlargement associated with mouth breathing, genetic disorders, and systemic conditions such as leukemia, Wegener’s granulomatosis, Crohn's disease, and sarcoidosis[14]. Diagnosis of HGF is primarily based on clinical findings. Key features include generalized, severe gingival overgrowth in the absence of a history of medication known to cause gingival enlargement. A positive family history can further support early diagnosis[15]. In HGF, overgrowth typically involves the attached gingiva, gingival margin, and interdental papillae, most commonly affecting the facial and lingual surfaces of the permanent teeth. Enlarged gingiva is typically firm and smooth, may be nodular, and shows minimal or no inflammation and is normal or pale in color. The maxillary arch is often more severely affected. In some cases, overgrowth is extensive enough to impede tooth eruption or nearly cover the clinical crowns.

The variability in presentation was evident across the four cases. Patient 1 and patient 2 represented classic nsHGF, with gingival enlargement as the sole manifestation; however, patient 2 also developed severe periodontitis, a common complication associated with pseudo-pocket formation. In contrast, patient 3 and patient 4 exhibited sHGF with extraoral features. The triad of gingival fibromatosis, congenital hypertrichosis, and macromastia observed in patient 3 is exceptionally rare, with only three sporadic cases reported previously. Identification of this phenotype across multiple generations within a single family suggests a potentially novel inherited syndrome. Patient 4’s presentation with hypertrichosis and clitoral hypertrophy suggested Zimmermann-Laband syndrome, although genetic confirmation was lacking[16]. Collectively, these cases highlight that a considerable proportion of sHGF cases may be attributable to as-yet-unidentified genetic mutations.

In addition, closer examination of each case revealed unique clinical features and individualized management considerations.

Patient 1, at 5 years of age, presented with near-complete coverage of the deciduous dentition, resulting in a “toothless” appearance and substantial psychosocial distress. Although recurrence rates are higher in children[17], gingivectomy was performed to expose the teeth and address esthetic concerns. At the 1-month follow-up, the patient and her family reported high satisfaction, highlighting the importance of considering quality of life in treatment decisions for young children.

Patient 2 presented with a distinctive combination of nsHGF and severe periodontitis. Gingival enlargement created deep pseudo-pockets, facilitating plaque accumulation and secondary inflammatory destruction. Although deep pockets persisted at the 2-year follow-up despite surgical therapy (data not shown), periodontal parameters improved significantly by the 3-year follow-up. This delayed response highlights the need for long-term supportive care in patients with HGF and periodontitis, as tissue remodeling may require an extended period.

Patients 3 and 4 illustrate the complex complications associated with syndromic HGF, including delayed tooth eruption, malalignment, and caries related to compromised oral hygiene. Patient 3, who presented with the rare triad of gingival fibromatosis, hypertrichosis, and macromastia, underwent multidisciplinary management. Although orthognathic surgery was recommended, the patient declined, and orthodontic treatment alone achieved substantial improvement in occlusion and facial profile at the 2-year follow-up. Patient 4, despite a comprehensive treatment plan, received only periodontal surgery and was subsequently lost to follow-up, highlighting challenges in maintaining long-term adherence in pediatric populations.

Taken together, these four cases illustrate the broad clinical spectrum of HGF and highlight the need for individualized management based on the patient age, disease severity, syndromic involvement, and long-term to care. This report has several limitations. Loss of patient 4 to follow-up limited assessment of long-term outcomes in that case. In addition, the absence of a genetic diagnosis in patients 3 and 4 highlights ongoing challenges in elucidating the full genetic landscape of syndromic HGF.

CONCLUSION

In summary, this report highlights that HGF encompasses a broad clinical spectrum, ranging from isolated gingival involvement to complex syndromic manifestations. Diagnosis requires careful evaluation of family history and thorough assessment for associated extraoral features. Given the functional, aesthetic, and psychological impact of the condition, management should be early, multidisciplinary, and individualized. Long-term follow-up is essential to monitor for recurrence and maintain periodontal health.