Hereditary gingival fibromatosis (HGF) is an uncommon slow-growing fibrous overgrowth characterized by connective tissue accumulation. It presents as an isolated feature or as a manifestation of any syndrome. Various syndromes associated with HGF are inherited by autosomal dominant/recessive/X-linked traits. Zimmermann-Laband syndrome (ZLS) is a rare, autosomal dominant inherited disease manifested with gingival fibromatosis (GF), nose and ears abnormalities, and hypoplastic/dysplastic nails or terminal phalanges of hand and feet. Although the pattern of inheritance was found to be both autosomal dominant and recessive traits, the molecular basis is still unclear. This report presents a possible case of ZLS-associated HGF in a 25-year-old female patient who presents with GF, hypertrichosis, and other syndrome-related features. Her father was similarly affected whereas her mother and sibling were asymptomatic. The patient and her family members were explained about the condition and surgical periodontal therapy was carried out for the patient to improve esthetics and was followed up regularly. Esthetics was significantly improved and no recurrence was noted at the end of 6 months.

OBJECTIVE: The objective of this study was to detect the undiscovered bioinformatics information about hereditary gingival fibromatosis and find focuses from published datasets.
METHODS: Two published datasets containing gingival tissue expression profiles of HGF and healthy groups were collected from GEO database. GSE4250 was utilized for cardinality analysis, including the differentially expressed gene analysis, enrichment analyses, hierarchical clustering analysis, and protein-protein interaction network. Key genes were obtained from the protein interaction network plot. GSE58482 was utilized for validation.
RESULTS: Analysis of the expression profiling by array, there were 785 genes (380 upregulated genes, 405 downregulated genes) expressed differentially between HGF gingival tissue and healthy gingival tissue. KEGG and GO enrichment analyses obtained candidate pathways. Differentially expressed genes were associated with activated pathways like skin barrier pathway and cornified envelope pathway. Repressed pathways included ion homeostasis pathway, receptor ligand activity pathway, and cell population proliferation pathway. Key genes such as F2R, TGM7, and MMP13 were confirmed with differential expression by external validation.
CONCLUSIONS: By bioinformatics approaches, we found new discoveries including several pathways and key genes. These discoveries deserve attention and research in the future.

Hereditary gingival fibromatosis (HGF) is an uncommon condition characterized by a benign, local, or diffuse gingival overgrowth. It may cover the teeth partially or totally, causing essential aesthetic, phonetic, and masticatory disorders. In this report, we discuss a case of an 11-year-old boy who presented with severe gingival enlargement. The diagnosis of HGF was made based on clinical examination and family history, with two of the patient\'s brothers and his paternal aunt being affected with the same disease. The patient was managed with electrosurgery under general anesthesia.

BACKGROUND: Hereditary gingival fibromatosis (HGF) is a rare condition characterized by slowly progressive overgrowth of the gingiva. The severity of overgrowth may differ from mild causing phonetic and masticatory issues, to severe resulting in diastemas or malposition of teeth. Both, autosomal-dominant and autosomal-recessive forms of HGF are described. The aim of this review is a clinical overview, as well as a summary and discussion of the involvement of candidate chromosomal regions, pathogenic variants of genes, and candidate genes in the pathogenesis of HGF. The loci related to non-syndromic HGF have been identified on chromosome 2 (GINGF, GINGF3), chromosome 5 (GINGF2), chromosome 11 (GINGF4), and 4 (GINGF5). Of these loci, pathogenic variants of the SOS-1 and REST genes inducing HGF have been identified in the GINGF and the GINGF5, respectively. Furthermore, among the top 10 clusters of genes ranked by enrichment score, ATP binding, and fibronectin encoding genes were proposed as related to HGF.
CONCLUSIONS: The analysis of clinical reports as well as translational genetic studies published since the late\'90s indicate the clinical and genetic heterogeneity of non-syndromic HGF and point out the importance of genetic studies and bioinformatics of more numerous unrelated families to identify novel pathogenic variants potentially inducing HGF. This strategy will help to unravel the molecular  mechanisms as well as uncover specific targets for novel and less invasive therapies of this rare, orphan condition.

Hereditary gingival fibromatosis (HGF) is a proliferative fibrous lesion causing severe gingival enlargement, affecting the esthetics, as well as posing various periodontal problems. This case report addresses the diagnosis and treatment of one such rare case of HGF where the patient presented with generalized diffuse gingival enlargement involving the maxillary and mandibular arches extending on the buccal and lingual/palatal surfaces and covering the incisal/occlusal third of the tooth, resulting in altered esthetics, difficulty in speech, and mastication. Gingivectomy was carried out in all the four quadrants using diode laser. The healing was uneventful; the patient was satisfied with her esthetics and was able to resume her oral hygiene practices. Even though recurrence cannot be predicted, the risk of recurrence can be outweighed with the psychological and functional benefits. Long-term follow-up will be required to evaluate the predictability of the different surgical techniques.

Hereditary gingival fibromatosis (HGF) is a rare condition affecting the gingiva and may or may not be a clinical feature of other syndromes. It has been classified as a nondental biofilm-induced gingival disease. The pathogenesis of this condition has been poorly understood till date. Although different genetic mutations have been implicated to play a role, there is considerable interest on an addition mutation of Son of Sevenless-1 (SOS-1) gene. We report a case of a 27-year-old male patient who came to us with the complaint of enlarged gums of several years\' duration. There were other members in his family who were similarly affected. After the clinical diagnosis of HGF was confirmed, the patient and his available family members were subjected to a genetic analysis for identification of mutation in SOS-1 gene, which turned out to be negative. The patient was treated with nonsurgical periodontal therapy and is under regular follow-up. To the best of our knowledge, this is the first study to assess SOS-1 mutation in an Indian family.

Our aim is to describe a family with a nonsyndromic form of hereditary gingival fibromatosis (HGF) and discuss genetic characteristics of this rare disease by reviewing reported cases. A mother and three descendants were diagnosed with HGF. There was marked variable expressivity: from severe generalized gingival overgrowth in a 16-year-old boy (the proband) to minimal manifestations in the mother. The proband was submitted to gingivectomy and gingivoplasty. In younger siblings, the disease remained stable for 5 years, suggesting that clinical surveillance is a good option. The diagnosis was supported by histopathological examination. Analysis of this family and literature-reported cases supports that HGF most frequently shows an autosomal dominant inheritance with high penetrance and variable expressivity. Neomutations and gonadal mosaicism do not seem to be a rare event. Although five loci have been mapped by linkage analysis, only two genes, SOS1 and REST, were identified in four families.

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.
遗传性牙龈纤维瘤病是一种罕见的家族遗传性疾病，以牙龈组织缓慢、渐进性增生为主要特征。本文对1例遗传性牙龈纤维瘤病家族进行报道及文献回顾。.

OBJECTIVE: Hereditary gingival fibromatosis (HGF) is a rare oral disease characterized by either localized or generalized gradual, benign, non-hemorrhagic enlargement of gingivae. Although several genetic causes of HGF are known, the genetic etiology of HGF as a non-syndromic and idiopathic entity remains uncertain.
METHODS: We performed exome and RNA-seq of idiopathic HGF patients and controls, and then devised a computational framework that specifies exomic/transcriptomic alterations interconnected by a regulatory network to unravel genetic etiology of HGF. Moreover, given the lack of animal model or large-scale cohort data of HGF, we developed a strategy to cross-check their clinical relevance through in silico gene-phenotype mapping with biomedical literature mining and semantic analysis of disease phenotype similarities.
RESULTS: Exomic variants and differentially expressed genes of HGF were connected by members of TGF-β/SMAD signaling pathway and craniofacial development processes, accounting for the molecular mechanism of fibroblast overgrowth mimicking HGF. Our cross-check supports that genes derived from the regulatory network analysis have pathogenic roles in fibromatosis-related diseases.
CONCLUSIONS: The computational approach of connecting exomic and transcriptomic alterations through regulatory networks is applicable in the clinical interpretation of genetic variants in HGF patients.

Hereditary gingival fibromatosis (HGF) is an uncommon gingival disease of attached gingiva, which is manifested as localized or generalized form. The HGF inheritance is transmitted through both autosomal dominant and recessive modes. Here, we are discussing a rare case report of an 8-year-old child with gingival fibromatosis in mixed dentition, which caused damage to his speech, mastication, and esthetics and led to significant change in his facial profile. The patient noticed that the gingival enlargement was simultaneous with deciduous dentition eruption and gradually covered entire dentition. Gingival enlargement covered all teeth anteriorly and posteriorly and only occlusal surfaces were visible. The enlarged tissue was resected by the external bevel gingivectomy under general anesthesia arch wise. The postoperative healing was satisfactory, uneventful, and there was significant change in patient\'s esthetics. Patient has been kept on regular recall visits. How to cite this article: Gandhi M, Tandon S, Sharma M, Vijay A. Nonsyndromic Gingival Fibromatosis: A Rare Case Report. Int J Clin Pediatr Dent 2018;11(3):250-253.