Looking back and beyond the 2017 diagnostic criteria for hypermobile Ehlers‐Danlos syndrome: A retrospective cross‐sectional study from an Italian reference center

Abstract

The most common conditions with symptomatic joint hypermobility are hypermobile Ehlers‐Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). Diagnosing these overlapping connective tissue disorders remains challenging due to the lack of established causes and reliable diagnostic tests. hEDS is diagnosed applying the 2017 diagnostic criteria, and patients with symptomatic joint hypermobility but not fulfilling these criteria are labeled as HSD, which is not officially recognized by all healthcare systems. The 2017 criteria were introduced to improve diagnostic specificity but have faced criticism for being too stringent and failing to adequately capture the multisystemic involvement of hEDS. Herein, we retrospectively evaluated 327 patients from 213 families with a prior diagnosis of hypermobility type EDS or joint hypermobility syndrome based on Villefranche and Brighton criteria, to assess the effectiveness of the 2017 criteria in distinguishing between hEDS and HSD and document the frequencies of extra‐articular manifestations. Based on our findings, we propose that the 2017 criteria should be made less stringent to include a greater number of patients who are currently encompassed within the HSD category. This will lead to improved diagnostic accuracy and enhanced patient care by properly capturing the diverse range of symptoms and manifestations present within the hEDS/HSD spectrum.

Phenotypic Clusters and Multimorbidity in Hypermobile Ehlers-Danlos Syndrome

“…Although these conditions have previously been linked to hEDS, our study provides valuable prevalence data, offering insights into their impact on a broader population with hEDS. 17 It should be noted that comorbid conditions, such as MCAS and POTS are likely underdiagnosed in the population with hEDS, and therefore, our data represent a conservative estimate.…”

Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review

“…Mutations occurring in collagen genes, notably types III and V, are significant contributors to the development of Ehlers-Danlos syndrome (EDS). Furthermore, the functions of other ECM constituents, such as tenascin XB (TNXB), vitronectin (VTN), and proteoglycans and glycosaminoglycans (GAGs), are explored within the context of regulating connective tissue equilibrium and understanding pathogenesis [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. Acquiring insights into these mechanisms is imperative for the advancement of targeted therapeutic interventions and enhancing the clinical management of connective tissue disorders [37][38][39][40].…”

“…Several mutations in type V collagen have been discovered in JHS/EDS-HT, including COL5A1 and COL5A2 (Figure 1). In addition to mutations in types I and III collagen (COL1A1, COL1A2, and COL3A1), these mutations exhibit an autosomal dominant inheritance pattern in JHS/EDS-HT [23][24][25][26]. Approximately fifty percent of point mutations are observed within the glycine residues of the G-X-Y tripeptide unit, constituting the repetitive sequence of the triple helix [41,42].…”

“…Besides these points, nowadays, attempts to diagnose this syndrome are based on the 2017 diagnostic criteria [8,19,20], since no instrumental, histopathological, structural, or molecular information is currently available to be used as a specific biomarker [21,22]. However, some patients whose signs and symptoms do not fit completely with the 2017 diagnostic criteria are not officially recognized by all healthcare systems and are categorized only as having hypermobility syndrome disorder (HSD) [23,24].…”