Biomarkers for Ehlers-Danlos Syndromes: There Is a Role?

Laura Caliogna,Alice Maria Brancato,Viviana Guerrieri,Mario Mosconi,Alberto Castelli,Gianluigi Pasta,Valentina Bina,Federico Alberto Grassi,Eugenio Jannelli,Salvatore Annunziata,Alessandro Ivone

doi:10.3390/ijms221810149

Abstract

Ehlers-Danlos syndromes (EDS) are an inherited heterogeneous group of connective tissue disorders characterized by an abnormal collagen synthesis affecting skin, ligaments, joints, blood vessels, and other organs. It is one of the oldest known causes of bruising and bleeding, and it was described first by Hippocrates in 400 BC. In the last years, multiple gene variants involved in the pathogenesis of specific EDS subtypes have been identified; moreover, new clinical diagnostic criteria have been established. New classification models have also been studied in order to differentiate overlapping conditions. Moreover, EDS shares many characteristics with other similar disorders. Although distinguishing between these seemingly identical conditions is difficult, it is essential in ensuring proper patient care. Currently, there are many genetic and molecular studies underway to clarify the etiology of some variants of EDS. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. In this review, we focused on the study of two of the most common forms of EDS—classic and hypermobile—by trying to identify possible biomarkers that could be of great help to confirm patients’ diagnosis and their follow up.

Highlights

Ehlers-Danlos syndromes (EDS), are a group of heritable connective tissue disorders (HCTDs) characterized by a variable degree of skin hyperextensibility, joint hypermobility, and tissue fragility, that were firstly described by Hippocrates in 400 BC [1]
In this review we evaluated the potential diagnostic use of some biomarkers associated with the clinical picture of EDS diseases, which could be used in the future for a more accurate diagnosis, prognosis, and follow up of EDS patients
Many genes were studied to identify hypermobile type of EDS (hEDS)’s causal factors, but little was found, showing the heterogeneous origin of these conditions. These variants have only been found in a small percentage of hEDS patients, leaving most cases without a genetic diagnosis

Summary

Introduction

Ehlers-Danlos syndromes (EDS), are a group of heritable connective tissue disorders (HCTDs) characterized by a variable degree of skin hyperextensibility, joint hypermobility, and tissue fragility, that were firstly described by Hippocrates in 400 BC [1]. The incidence of EDS is best estimated to be between 1 in 25,000 and 1 in 5000, varying greatly between the various types of EDS. The most common EDS type seems to be the hypermobile (hEDS), with an incidence ranging between 1 in 10,000 and 1 in 15000, followed by classic. EDS (cEDS), which is estimated to affect 1 per 10,000 to 1 per 20,000 people [2]. Both vascular EDS (vEDS) and kyphoscoliotic EDS have a smaller incidence, ranging between 1/50,000 and 1/200,000 [3]. 13 types with 19 different causal genes mainly involved in collagen and extracellular matrix (ECM) synthesis and maintenance. The main cause of classical and vascular

Methods

Results

Discussion

Conclusion