Fibromatosis hyaline juvenile M72.8

Very rare, congenital mutation in the anthrax toxin receptor 2 gene (also CMG2 gene = capillary morphogenesis factor 2 protein gene), which is localized on chromosome 4q21.21. The mutation manifests itself between the 2nd month of life and the 4th year of life and is probably autosomal recessive.

The disease presents as a systemic disease(hyalinosis) with multiple, very coarse, fibromatous tumors mainly on the head, often also periarticular, as well as gingival hypertrophy and joint contractures. Increased synthesis of chondroitin sulfate by fibroblasts has been demonstrated.

Rare; fewer than 150 cases have been described worldwide.

Mutation in the ANTXR2 gene (CMG2 gene). The function of this gene is not known. It encodes a protein that is an intergrin-like receptor for laminin and collagen IV. This plays an important role in cell-matrix interactions.

Numerous, partly ulcerating, coarse, different sized, slowly growing nodes, especially on the head. Gingival hyperplasia. Bone and joint destruction with osteolysis, formation of severe joint contractures. Scoliosis.

Tumor parenchyma consists of pale fibroblast-like cells with granulated cytoplasm in amorphous, eosinophilic, PAS-positive, hyaline basic substance.

Rahman et al (2002) reported on 2 Indian families in which 4 individuals had hyaline fibromatosis. The families were presumably unrelated but came from the same small village. The patients presented in early childhood with progressive development of multiple subcutaneous swellings and nodules on the scalp, face, extremities, and trunk. Large nodules on the hands and feet were nondisplaceable over the underlying articular cartilage. Other features included gingival hyperplasia, and progressive severe joint contractures; further osteopenia or osteolysis, and massive hyaline deposits in the dermis.

El-Kamah et al (2010) reported on 3 Egyptian siblings born to consanguineous parents who suffered from severe hyaline fibromatosis in infancy. The first child died of respiratory distress at 3 days of age. The second child had multiple nodular skin swellings, painful joint contractures, gingival hyperplasia, repeated pneumonias, and persistent diarrhea. It died of cardiac arrest at the age of 4 years. The third child had painful joint contractures and died of diarrhea at 2 years of age. Genetic analysis revealed a homozygous mutation in the ANTXR2 gene (1074delT; 608041.0008).

Denadai et al (2012) reported a sibling and three other unrelated patients, all of Brazilian origin, with childhood hyaline fibromatosis. The siblings developed pearly skin papules on the face and neck and cutaneous nodules on the ears, scalp, and fingers at 3 and 8 months of age, respectively. The girl suffered from recurrent diarrhea and failure to thrive during the first 2 years of life. Her brother developed numerous skin lesions all over the body, including some that confluent into plaques on the neck and buttocks; further gingival hyperplasia and joint contractures, severe failure to thrive, diarrhea, joint contractures.

The last patient was a 20-year-old male who was confined to a wheelchair due to postural deformities and severe contractures in several joints. He had perl-like and nodular skin lesions, gingival hyperplasia, and joint contractures since the first months of life. Patient radiographs showed osteolytic bone lesions. Duodenal biopsy of a patient with diarrhea showed deposits of hyalinized material. Histologic analysis of the skin lesions showed proliferation of spindle cells without atypical features that formed strands in a homogeneous and hyaline eosinophilic material within the dermis. The material was PAS-positive and resistant to diastasis. Some of the lesions were ulcerated.

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