Juvenile hyaline fibromatosis and infantile systemic hyalinosis: a unifying term and a proposed grading system.

BACKGROUND: It has been suggested that juvenile hyaline fibromatosis and infantile systemic hyalinosis represent different severities of the same disease. OBJECTIVE: We sought to redefine these disorders clearly to establish a common inclusive terminology. PATIENTS: The study included two children with early onset of similar pink papulonodular skin lesions and marked gingival hyperplasia. The first case was characterized by flexion contractures of the large joints, fractures, persistent diarrhea, recurrent chest infections, and retarded physical growth. The second patient had large swellings on the scalp and knees without systemic involvement. RESULTS: Radiologic examination revealed fractures and osteolytic bone lesions in the first case, and soft tissue masses in the second case. Laboratory tests showed anemia in both cases, and hypogammaglobulinemia, hypoalbuminemia, and electrolyte imbalance in the first case. Histopathological and ultrastructural evaluation demonstrated hyalinized fibrous tissue in the dermis in both cases. LIMITATIONS: Genetic studies were unavailable. CONCLUSION: Juvenile hyaline fibromatosis and infantile systemic hyalinosis share many common features that strongly support consideration of these conditions as different expressions of the same disorder. We propose a common term, "hyaline fibromatosis syndrome," which can be divided into mild, moderate, and severe subtypes.

Clinical and histomorphometric characteristics of three different families with hereditary gingival fibromatosis.

OBJECTIVE: To examine the histomorphologic and histomorphometric features of tissue from 3 unrelated families with hereditary gingival fibromatosis (HGF). STUDY DESIGN: Twelve affected individuals from 3 HGF families and 3 control subjects were evaluated. Gingival samples were fixed in formalin and embedded in paraffin for hematoxylin and eosin stain to count the number of fibroblast and inflammatory cells. Sirius red staining was performed to quantitate the amount of collagen present. RESULTS: Histomorphologic analysis of HGF showed extension of epithelial rete ridges into the underlying lamina propria and the presence of collagen bundles in the connective tissue. Analysis of the mean area fraction of collagen showed that there were significant increases in the collagen fraction for all HGF types compared with control subjects (P < .05). There were significant increases in the number of fibroblasts for HGFa and HGFb compared with control subjects (P < .05). The number of fibroblasts for HGFc were similar to that for control subjects. CONCLUSIONS: The collagen fraction was significantly greater in all HGF types compared with controls. The number of fibroblasts was significantly increased in 2 of the 3 HGF types compared with controls. These data indicate that different mechanisms may be responsible for tissue enlargement in different forms of HGF.

Fibromatosis gingival hereditaria: reporte de un caso familiar de cuatro miembros / Hereditary fibromatosis gingival: report of family case of four members

La presencia de deformidades mucogingivales generalmente tiene un impacto en cuanto se refiere a la estética y función, la variedad de presentaciones de estas deformidades impide hacer una única definición. Las deformidades mucogingivales como se define aqui, puede ser congénita, del desarrollo o por inducción farmacológica. Estas pueden ocurrir alrededor de piezas dentarias naturales o de implantes, pueden localizarse en tejidos blandos o ser asociados con defectos de la estructura ósea. Pueden también mostrar diferentes grados de severidad o extensión. Cualquier clasificación de deformidades mucogingivales deberán incluir un método de identificación de las diferentes condiciones que incluyan un buen diagnóstico, identificación etiológica, investigación y el tratamiento adecuado además de su evolución posterior. Este es el reporte de un caso familiar de cuatro hermanas que presentaron y presentan la enfermedad, cuyas evidencias clínicas y la historia de la enfermedad familiar hacen pensar en una fibromatosis gingival hereditaria, asociadas a la no erupción de piezas dentarias, especialmente premolares superiores e inferiores que han provocado la formación de quistes dentigeros, además de un probable hirsutismo.

A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1.

Hereditary gingival fibromatosis (HGF) is a rare, autosomal dominant form of gingival overgrowth. Affected individuals have a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of the oral masticatory mucosa. Genetic loci for autosomal dominant forms of HGF have been localized to chromosome 2p21-p22 (HGF1) and chromosome 5q13-q22 (HGF2). To identify the gene responsible for HGF1, we extended genetic linkage studies to refine the chromosome 2p21-p22 candidate interval to approximately 2.3 Mb. Development of an integrated physical and genetic map of the interval identified 16 genes. Sequencing of these genes, in affected and unaffected HGF1 family members, identified a mutation in the Son of sevenless-1 (SOS1) gene in affected individuals. In this report, we describe the genomic structure of the SOS1 gene and present evidence that insertion of a cytosine between nucleotides 126,142 and 126,143 in codon 1083 of the SOS1 gene is responsible for HGF1. This insertion mutation, which segregates in a dominant manner over four generations, introduces a frameshift and creates a premature stop codon, abolishing four functionally important proline-rich SH3 binding domains normally present in the carboxyl-terminal region of the SOS1 protein. The resultant protein chimera contains the wild-type SOS1 protein for the N-terminal amino acids 1-1083 fused to a novel 22-amino acid carboxyl terminus. Similar SOS1 deletion constructs are functional in animal models, and a transgenic mouse construct with a comparable SOS1 chimera produces a phenotype with skin hypertrophy. Clarification of the functional role of this SOS1 mutant has implications for understanding other forms of gingival fibromatosis and corrective gingival-tissue management.

Ultrastructural aspects of connective tissue in hereditary gingival fibromatosis.

OBJECTIVE: The purpose of this study was to analyze the ultrastructure of gingival connective tissue from patients in one family affected by hereditary gingival fibromatosis (HGF). STUDY DESIGN: Electron microscopic examination was performed with gingival tissue from 10 patients from a Brazilian family with 132 members. Fifty of 96 persons at risk for this disorder were affected, which is consistent with an autosomal dominant pattern of inheritance. RESULTS: The extracellular matrix showed flocculent material and collagen fibrils with structural abnormalities and variation in diameter. Increased numbers of oxytalan fibers were identified; however, elastic fibers were rare in the analyzed areas. CONCLUSIONS: The structural alterations found in HGF appear similar to those described in certain other heritable collagen disorders, suggesting that HGF should be included in the group of hereditary diseases in which connective tissue alterations have a distinct pattern, in contrast to reactive fibrotic gingival enlargements with no genetic component.

Gingival fibromatosis.

Presented in this paper is a clinico-pathological report of 11 cases of gingival fibromatosis. Of the 11 patients in our series, 2 cases (18.2%) with family history began to have symptom from age of 3, which is manifested by the involvement of whole gum. 9 patients (81.8%), for which the etiology was unknown, had onset of the disease at the periods of deciduous dentition, mixed dentition or permanent dentition, with localized or overall involvement of gingiva. The disease is characterized by diffuse or localized proliferation of gum. Microscopically, the proliferating gum tissue revealed well-developed fibrotic structure with few cells; and the fibers were densely arranged without clear boundary. The fibrotic tissues showed a diminishing of blood vessels and the infiltration of inflammatory cells is not conspicuous.

[Hereditary gingival fibromatosis].

Fibromatosis may be defined as diffuse poorly circumscribed overgrowth of the fibrous tissue that infiltrates adjacent normal tissues. They are difficult to eradicate surgically, and recur but not metastasize. Gingival fibromatosis is generally regarded as a disease that leads to an extensively diffuse and remarkable hyperplasia of the maxillo-mandibular gingiva. Occasionally, this lesion covers all teeth. The histogenesis of the fibromatosis remains unexplained. Trauma, endocrine, idiopathic factors and genetic factors have been implicated, but it is uncertain whether any of then play a major role in the development of the disease. Occasional cases with familial history have been reported. The treatment of choice would appear to been block resection of the tumor and surrounding normal structures. Although, this lesion has a high recurrent rate. For this reason, in many of the case reports, that it has been recommended that the follow up period is considerably less than three years.

Hypertrichosis universalis congenita: a separate entity, or the same disease as gingival fibromatosis?

Hypertrichosis universalis congenita is an extremely rare disorder characterized by generalized hypertrichosis. It is generally accepted as being inherited as an autosomal dominant trait with varying expression. Many aspects of this disease are still unknown. Several reports associating hypertrichosis and gingival fibromatosis raise the question of whether they are separate entities or the same disease with different expressions of the underlying process. Hypertrichosis universalis congenita occurred in a 6-year-old girl without known family history. Her facial features were simian-like and her gingiva was moderately hyperplastic. We pose the question of whether or not these phenomena are related.

Heterogeneity in gingival fibromatosis.

A review of cases indicated that gingival fibromatosis occurs in a variety of genetic entities. High risk for epilepsy and oligophrenia is associated if hypertrichosis is present. Other entities are symmetrical gingival fibromatosis; Zimmermann-Laband syndrome with bone, ear, nose and nail defects and hepatosplenomegaly; Murray syndrome with multiple hyaline dermal tumors; Rutherfurd syndrome with corneal dystrophy; Cowden syndrome with hypertrichosis, oligophrenia and giant fibroadenomatosis of breasts and Cross syndrome of hypopigmentation, oligophrenia and athetosis.