Hereditary gingival fibromatosis

There may or may not be any evidence of history of HGF in the family nor any usage of taking long-term medicines for any particular disease when it comes to diagnosing HGF. There also may or may not be any signs of medical and/or family history of mental retardation, hypertrichosis, nor clinical symptoms that can be associated with gingival enlargement. Although, enlargement of gingiva, interdental papilla, hindered speech, and secondary inflammatory changes taking place in the mouth commonly at the marginal gingiva are all very indicative of this condition. Commonly the patient will have mandibular and maxilliary inflammation and overgrowth as opposed to the traditional pink, firm, and fleshy consistency of healthy gingiva. The patient's jaw may also appear distorted because of the gingiva enlargements. Overgrowth of the gingiva can range from slightly covering the surface of teeth or it can even completely cover the surrounding teeth. The patient can also experience damage or loss of teeth.[1][2][3][4][5][6][7][8][9][10][11][12]

Though much more research needs to be done, researchers have mostly agreed that a mutation in SOS1, son-of-sevenless gene, is responsible for this disease.[1][4][5][6] SOS1 is a guanine nucleotide-exchange factor that functions in the transduction of signals that control cell growth and differentiation. A mutation in the SOS1 gene results in a single nucleotide insertion.[6] Specific linkage studies have localized the mutation for isolated, nonsyndromic autosomal dominant forms of gingival fibromatosis to chromosomes 2 and 5, more specifically 2p21-p22 and 5q13-q22.[1]

Genetic linkage studies are among the most popular methods of study to look at the mechanism of this HGF. Genetic linkage studies have found to localize genetic loci for autosomal dominant forms of HGF to chromosome 2p21-p22 (indicative of HGF1) and chromosome 5q13-q22 (indicative of HGF2). Chromosome 2p21-p22 has been refined to an interval of ~2.3 Mb to construct an integrated physical and genetic map of the 16 genes interval. Here, a mutation is found in sequencing these 16 genes.[2]

There is an insertion of a cytosine between nucleotides 126,142 and 126,143 in codon 1083 of the SOS1 gene, meaning there is a mutation in SOS1. This causes a problem because SOS1 introduces a frameshift mutation and creates a premature stop codon. Also, it can segregate over generations, most commonly four. Once it causes a premature stop codon, the chromosome loses four important proline-rich SH-3 binding domains in the carboxyl-terminal region of the SOS1 protein. As a result, the N-terminal amino acids for SOS1 is fused into a 22–amino acid carboxyl terminus.[2] Researchers claim that this mutation in the SOS1 gene is a probable primary cause of this disease but limited information supports the mechanism of this claim.

There are very few ways to test a patient for HGF. Currently, the most common way to diagnose a patient is by means of a physical evaluation. The physician can make a physical evaluation of the patient and send them to a dentist or better yet a specialist like a periodontist to evaluate signs of gingival overgrowth, quality of gingiva, inflammation, mechanical difficulties of the mouth, tooth conditions, and any sort of discomfort.[3]

Aside from obvious physical symptoms seen in a physical evaluation, molecular tests can be run to check if there is a mutation in the SOS1 gene to confirm the diagnosis. If there is indeed a mutation in this gene coupled with the typical physical symptoms, then it is quite probable that a patient suffers from this disease. Also, looking at family history is also becoming more prominent in aiding to diagnose the patient. Otherwise, researchers are working to find new and better ways to test for the presence of HGF.[1][2][9]

Since this condition is generally agreed upon to be hereditary, nothing can be done to prevent HGF. However, in some cases where it can develop as a result of rare multi-system syndromes, such as: Zimmerman-Laband, Jones, Ramon Syndrome, Rutherford Syndrome, Juvenile Hyaline Fibromatosis, Systemic Infantile Hyalinosis, and Mannosidosis, it is best for one to simply monitors the possible progression for HGF with regular dental check-ups.[8]

If the patient's disease is treated by means of surgery, it is recommended that the patient undergoes post-surgical therapies for maintenance and periodic monitoring of gums for the sake of the possibility of re-occurrence of HGF.[8]

This disease has not been shown to be life-threatening or the cause of death in patients. However, treatment is necessary to maintain a healthy lifestyle.

Some researchers suggest that HGF is transmitted as a Mendelian trait since both autosomal dominant and autosomal recessive transmission has been reported since the early 1970s. (SOURCE 1) In more recent scientific literature, there is evidence in which pedigree analyses confirm autosomal dominant, autosomal recessive or even as X-linked inherited cases of the HGF trait.[11][12]

In 2002, researchers described the SOS1 gene and proved for the first time that a single-nucleotide–insertion mutation of the SOS1 gene on codon 1083 is the preliminary cause of HGF1 in humans. (Source 1) Later on in 2010, there was a case study done on a 16-year-old male with severe gingival overgrowth, almost covering all teeth. Researchers approached this issue with periodontics - a partial gingivectomy and flap surgery. This case study concluded that surgery followed by regular follow-ups is a good way to treat HGF despite the fact that the risks of re-occurrence of the condition remain high.[8]

Even more recently, a study was done in 2013 on a family that showed history of autosomal recessive inheritance of HGF. The study did not dismiss the return of HGF after treatment but did claim that general surgical intervention after scaling and root planning of teeth supplemented with good oral hygiene is good enough to prevent the re-occurrence of HGF. This case study also acknowledged how HGF can be part of a multi-system syndrome associated with disorders such as Zimmermann Laband syndrome (ear, nose, bone, and nail defects with hepatosplenomegaly), Rutherford syndrome (microphthalmia, mental retardation, athetosis, and hypopigmentation), Murray-Puretic Drescher syndrome and Ramon syndrome.[1]

• Chronic periodontitis
• Epidemiology of periodontal diseases
• Gingivitis
• Gum graft
• Periodontist
• Tooth loss
• Gingival recession

• American Academy of Periodontology Home Page
• Periodontal Disease as a Specific, albeit Chronic, Infection: Diagnosis and Treatment