Ultrastructural Collagen Markers in Ehlers Danlos Syndromes

Study Overview
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Brief Summary
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Establishing the diagnosis of Ehlers Danlos Syndromes (EDS)/generalized hypermobility spectrum disorders (G-HSD) is often problematic for patients. The absence of a precise unifying diagnosis in patients results in a significant emotional burden on the patient and caregivers, not to mention the hidden costs, including multiple recurring visits to several medical specialists and associated social and economic costs. To date, while collagen ultra-scale morphological heterogeneity has been used to comment on an EDS diagnosis, the mechanical properties of the collagen remain mostly unexplored. From a biophysical point of view, collagen affected with hEDS can be described as biomechanically deficient. In the case of EDS, the skin's abnormal elasticity can be directly related to the organization of the collagen network within the dermis. Quantitative Nanohistology (QNH) is a newer method to evaluate both the structural and mechanical properties of collagen in-situ histological sections. Therefore, the aim of this study is to define histo-biophysical markers of two most common types of EDS i.e. classical EDS (cEDS) & hypermobile EDS (hEDS) at the single collagen fibrils level and matrix and to further explore the origin of collagen fibril properties deficiency in hEDS and cEDS.

Official Title
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Decrypting the Ultrastructural Collagen Markers Using Quantitative Nano Histology: A Quest for Newer Diagnostic Test in Hypermobile Ehlers-Danlos Syndrome

Conditions
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Ehlers-Danlos Syndrome, Classical Ehlers-Danlos Syndrome, Hypermobile EDS (hEDS)

Intervention / Treatment
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* Other: Skin Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged between 18 and 60 years who can provide informed consent in English Able to read, speak, and comprehend English without the assistance of a translator Have been diagnosed with hypermobile EDS as per the 2017 EDS criteria; or with genetically confirmed classical EDS (age and sex-matched). This diagnosis is carried out by the UHN GoodHope EDS clinic routinely for all patients on the basis of clinical exam and genetic testing, if indicated. Exclusion Criteria: Subjects under the age of 18 Unable to speak, read and comprehend English Unable to provide consent (cognitive impairment) Pregnant women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals with hypermobile EDS<br>Skin biopsy collection | Other: Skin Biopsy<br>* Skin biopsy specimens will be collected for both groups and subjected to quantitative nano histology using atomic force microscopy to assess for structural profile of a single collagen fibril<br>|
| Individuals with classical EDS<br>Skin biopsy collection | Other: Skin Biopsy<br>* Skin biopsy specimens will be collected for both groups and subjected to quantitative nano histology using atomic force microscopy to assess for structural profile of a single collagen fibril<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to analyze percentage prevalence of abnormal morphological markers of single collagen fibril using atomic force microscopy | systemic nanoscale imaging to investigate the presence of morphological markers associated with each EDS type and compared to the normative data from the Bozec-lab obtained from healthy volunteers. These markers include fibrils D-banding periodicity, unwinding of the fibrils, variation in fibrils registration, and finally, cylindrical homogeneity (of the fibril | 3 months |