Biomarker for Hyaline Fibromatosis Syndrome (BioHFS) (BioHFS)

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

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

Study Overview

• Status: Withdrawn
• Conditions: Skin and Connective Tissue Diseases; Hyaline Membrane Disease; Hyalinosis; Juvenile Hyaline Fibromatosis; Fibromatosis Hyalinica Multiplex Juvenilis

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 Type: Observational

Contacts and Locations

Study Locations

• Germany
  • Rostock, Germany, 18055
    • Centogene AG
• India
  • Mumbai, India, 400705
    • NIRMAN Navi Mumbai Institute of Research In Mental And Neurological Handicap/Pediatric Geneticist
• Sri Lanka
  • Colombo 8, Sri Lanka, 00800c
    • Lady Ridgeway Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Hyaline fibromatosis syndrome or high-grade suspicion for Hyaline fibromatosis syndrome

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observation; Patients with Hyaline fibromatosis syndrome or high-grade suspicion for Hyaline fibromatosis syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: CENTOGENE GmbH Rostock

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2018
• Primary Completion (ACTUAL): February 28, 2021
• Study Completion (ACTUAL): February 28, 2021

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Hyaline Fibromatosis Syndrome
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Neoplasms, Connective Tissue; Infant, Premature, Diseases; Neoplasms, Fibrous Tissue; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome; Connective Tissue Diseases; Fibroma; Hyaline Membrane Disease; Hyalinosis, Systemic
• Other Study ID Numbers: BHFS 06-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No