Fibromatosis Hyalinica Multiplex Juvenilis, Hyaline Membrane Disease, Hyalinosis, Juvenile Hyaline Fibromatosis, Skin and Connective Tissue Diseases
Conditions
Keywords
Hyaline Fibromatosis Syndrome, Biomarker
Brief summary
Development of a new MS-based biomarker for the early and sensitive diagnosis of Hyaline fibromatosis syndrome from the blood
Detailed description
Hyaline fibromatosis syndrome (HFS) is rare autosomal recessive disease characterized by the deposition of amorphous hyaline material in skin and visceral organs. It represents a disease spectrum with infantile systemic hyalinosis (ISH) being the severe form and juvenile hyaline fibromatosis (JHF) being the mild form. Dermatologic manifestations include thickened skin, perianal nodules, and facial papules, gingival hyperplasia, large subcutaneous tumors on the scalp, hyperpigmented plaques over the metacarpophalangeal joints and malleoli, and joint contractures. ISH shows a severe visceral involvement, recurrent infections, and early death. The lesions appear as pearly papules or fleshy nodules. The severity is variable. Some individuals present in infancy and have additional visceral or systemic involvement, which can lead to early death. These patients may show intractable diarrhea and increased susceptibility to infection. Other patients have later onset of a milder disorder affecting only the face and digits. Additional features include gingival hypertrophy, progressive joint contractures resulting in severe limitation of mobility, osteopenia, and osteoporosis. Histologic analysis of skin lesions shows proliferation of spindle-shaped cells forming strands in a homogeneous and hyaline eosinophilic extracellular material in the dermis. New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.
Interventions
None listed
Sponsors
CENTOGENE GmbH Rostock
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent will be obtained from the parents before any study related procedures. * Patients of both gender older than 2 months * The patient has a diagnosis of Hyaline fibromatosis syndrome or a high-grade suspicion for Hyaline fibromatosis syndrome High-grade suspicion present, if one or more inclusion criteria are valid: * Positive family anamnesis for Hyaline fibromatosis syndrome * Coarse facies * Subcutaneous nodule * Gingival fibromatosis * Skeletal muscle atrophy * Progressive flexion contractures
Exclusion criteria
* No Informed consent from the parents before any study related procedures. * Patients of both gender younger than 2 months * No diagnosis of Hyaline fibromatosis syndrome or no valid criteria for profound suspicion of Hyaline fibromatosis syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sequencing of the Hyaline Fibromatosis Syndrome related gene | 4 weeks | Next-Generation Sequencing (NGS) of the ANTXR2 gene will be performed. The mutation will be confirmed by Sanger sequencing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Hyaline Fibromatosis Syndrome specific biomarker candidates finding | 24 months | The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker. |
Countries
Germany, India, Sri Lanka
Outcome results
None listed