Hypermobility spectrum disorders: A review

Abstract

It remains a clinical challenge identifying when joint hypermobility (JH) is responsible for pain. Previous nomenclature utilized terms such as (benign) joint hypermobility syndrome (JHS) but this was updated in 2017 as advances in genetics provide a basis for nearly all variants of Ehlers-Danlos syndrome (EDS) with the exception of hypermobile EDS (hEDS). New terminology describes hypermobility spectrum disorders (HSDs) as the updated term for JHS. Diagnosis of a subtype of HSDs should be considered in patients who have JH coupled with the presence of secondary musculo-skeletal manifestations (trauma, chronic pain, disturbed proprioception, and other manifestations) and at the exclusion of hEDS. Extra-articular manifestations are common. Treatment relies on management strategies for other chronic pain syndromes with a multidisciplinary approach likely optimal. Lifestyle modifications focus on weight loss and exercise. Physical therapy helps strengthen periarticular muscles, improving mobility. Pharmacologic therapies focus on judicious use of non-steroidal anti-inflammatory drugs and acetaminophen. Serotonin and norepinephrine reuptake inhibitor may help widespread pain. Avoidance of opioids remains prudent. The purpose of this review is to provide clinicians the rationale for the update in nomenclature, understand the musculoskeletal and extra-articular manifestations of the subtypes of HSDs, considerations when making the diagnosis, and treatment.

Joint Hypermobility Syndrome and Membrane Proteins: A Comprehensive Review

“…EDS constitutes a cluster of genetic disorders characterized by joint hypermobility, skin hyperextensibility, and other connective tissue anomalies. EDS arises from mutations in genes responsible for collagen or other connective tissue protein synthesis and maintenance [26]. The various EDS subtypes exhibit distinct clinical features and genetic mutations.…”

“…Diagnostic criteria for BJHS necessitate hypermobility in at least four joints without any concurrent medical condition, as indicated by a review article in Pediatric Rheumatology [26]. Despite its prevalence, current diagnostic criteria for JHS lack specificity, posing challenges in differentiating it from familial articular hypermobility and EDS.…”

“…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].…”

Correlation between benign joint hypermobility syndrome and headache in children and adolescents

“…A positive family history of hypermobility is common. BJHS is a condition that affects the joints, causing them to move beyond their normal range of motion [ 2 , 3 ].…”