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Hyaline fibromatosis syndrome in Adult
Other Resources UpToDate PubMed

Hyaline fibromatosis syndrome in Adult

Contributors: Edward Li PhD, Mari M. Batta DO, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Hyaline fibromatosis syndrome (HFS) is a family of rare genetic syndromes characterized by dysfunctional deposition of hyaline extracellular matrix materials in various tissues, resulting in papulonodular cutaneous lesions, gingival hypertrophy, joint contractures, and osteolytic lesions in infancy or early childhood. In very severe cases, there may be hyaline deposition in a variety of organ systems as well, such as the gastrointestinal tract.

HFS is extremely rare, with fewer than 100 cases reported worldwide, and affects both females and males with equal frequencies. Most of the reported cases have been in people with Turkish, Indian, and Moroccan ethnicity, but the true distribution is unknown.

HFS is the unifying designation that includes juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). Both disorders are caused by distinct deleterious mutations in the gene encoding for capillary morphogenesis protein 2 (CMG2; also known as anthrax toxin receptor 2 or ANTXR2) and are inherited in an autosomal recessive manner. CMG2 is a transmembrane protein that interacts with proteins in the extracellular matrix, such as collagen VI. It is hypothesized that CMG2 mediates lysosomal transport of collagen VI for degradation, and so mutations in CMG2 lead to the aberrant deposition and accumulation of collagen VI-containing extracellular hyaline material in various tissues.

The clinical presentation of ISH is similar to JHF but is more severe and occurs earlier, in infancy rather than childhood. It has been hypothesized that ISH mutations in CMG2 tend to cause protein truncations whereas JHF mutations tend to be missense mutations that might only mildly impact the function of the resulting protein.

The characteristic cutaneous lesions of HFS are asymptomatic and slow growing, commonly presenting as pink papules around the nose or nodules on the head, back, and knees. Gingival hypertrophy may be severe enough to interfere with feeding, leading to malnutrition and recurrent infections in infancy. The most debilitating disease features are the progressively painful joint contractures that limit mobility, often of the knees, elbows, fingers, and hip joints. Nodules can also form in internal organs and cause end-organ dysfunction. When this occurs in the intestines, affected individuals can present with severe diarrhea and a protein-losing enteropathy with associated failure to thrive.

HFS is frequently progressive and disabling, causing most adolescents and adults to become bedridden or wheelchair dependent. While individuals with JHF and mild disease manifestation can live into adulthood, those with severe disease often do not survive beyond childhood. The most severe cases of ISH can cause early life-threatening complications such as intractable diarrhea, recurrent infections, and multiorgan system failure and can result in death in early infancy.

A grading system for HFS has been proposed that classifies HFS into grade 1 (mild; limited to skin and gingival involvement), grade 2 (moderate; grade 1 + joint involvement), grade 3 (severe; grade 2 + signs of internal organ involvement), and grade 4 (lethal; grade 3 + signs of clinical decompensation).

For more information, see OMIM.

Codes

ICD10CM:
M72.8 – Other fibroblastic disorders

SNOMEDCT:
238861002 – Juvenile hyaline fibromatosis

Look For

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Gingival fibromatosis – Limited to gingiva.
  • Congenital generalized fibromatosis – Visceral involvement and death shortly after birth.
  • Winchester syndrome – Short stature, osteopenia, corneal opacities; skin lesions are not common.
  • Neurofibromatosis – Older children; look for café-au-lait macules, axillary or inguinal freckling, Lisch nodules, and neurofibromas.

Best Tests

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Management Pearls

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Therapy

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References

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Last Reviewed:03/18/2020
Last Updated:03/18/2020
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Hyaline fibromatosis syndrome in Adult
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Hyaline fibromatosis syndrome : Flexural distribution, Gingival hypertrophy, Joint contractures, Lytic bone lesions, Trunk, Hyperpigmented patches, Firm papules, Firm nodules
Clinical image of Hyaline fibromatosis syndrome
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