Biomarker for Hyaline Fibromatosis Syndrome (BioHFS)

Skin and Connective Tissue Diseases Clinical Trial

— BioHFS  

Official title:

Biomarker for Hyaline Fibromatosis Syndrome - An International, Multicenter, Epidemiological Protocol

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03196115
• Other study ID #: BHFS 06-2018
• Status: Withdrawn
• Start date: August 20, 2018
• Est. completion date: February 28, 2021

Study information

• Verified date: February 2023
• Source: CENTOGENE GmbH Rostock
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Development of a new MS-based biomarker for the early and sensitive diagnosis of Hyaline fibromatosis syndrome from the blood

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 28, 2021
• Est. primary completion date: February 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Connective Tissue Diseases
• Fibroma
• Fibromatosis Hyalinica Multiplex Juvenilis
• Hyaline Membrane Disease
• Hyalinosis
• Juvenile Hyaline Fibromatosis
• Skin and Connective Tissue Diseases

Locations

Country	Name	City	State
Germany	Centogene AG	Rostock
India	NIRMAN Navi Mumbai Institute of Research In Mental And Neurological Handicap/Pediatric Geneticist	Mumbai
Sri Lanka	Lady Ridgeway Hospital for Children	Colombo 8

Sponsors (1)

Lead Sponsor	Collaborator
CENTOGENE GmbH Rostock

Countries where clinical trial is conducted

Germany,  India,  Sri Lanka, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sequencing of the Hyaline Fibromatosis Syndrome related gene	Next-Generation Sequencing (NGS) of the ANTXR2 gene will be performed. The mutation will be confirmed by Sanger sequencing.	4 weeks
Secondary	The Hyaline Fibromatosis Syndrome specific biomarker candidates finding	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.	24 months

External Links

•   Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests.