Biomarker for Hyaline Fibromatosis Syndrome (BioHFS)

Sponsor

CENTOGENE GmbH Rostock (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03196115

Collaborator

(none)

1,000

Enrollment

Locations

33.4

Anticipated Duration (Months)

333.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hyalinosis Hyaline Membrane Disease Juvenile Hyaline Fibromatosis Fibromatosis Hyalinica Multiplex Juvenilis Skin and Connective Tissue Diseases

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Aug 20, 2018

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Observation Patients with Hyaline fibromatosis syndrome or high-grade suspicion for Hyaline fibromatosis syndrome

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centogene AG	Rostock	Germany	18055
2	NIRMAN Navi Mumbai Institute of Research In Mental And Neurological Handicap/Pediatric Geneticist	Mumbai	India	400705
3	Lady Ridgeway Hospital for Children	Colombo 8	Sri Lanka	00800c