What Is Ehlers-Danlos Syndrome?

Ehlers-Danlos Syndrome (EDS) is a group of heritable connective tissue disorders characterised by defects in the synthesis or structure of collagen and associated extracellular matrix proteins. Collagen is the primary structural protein of connective tissue, forming the scaffold of skin, tendons, ligaments, blood vessel walls, and organ capsules. When collagen is structurally abnormal or produced in insufficient quantity, the mechanical integrity of all collagen-dependent tissues is compromised — explaining why EDS presents with a clinically heterogeneous picture spanning skin fragility, joint hypermobility, vascular fragility, and systemic symptoms.

The 2017 International Classification recognises 13 subtypes of EDS, each associated with specific genetic mutations and clinical profiles. The most prevalent by a considerable margin is hypermobile EDS (hEDS), which accounts for the majority of presentations encountered in manual therapy practice. hEDS remains the only subtype without an identified causative genetic mutation, diagnosed on clinical criteria alone. The rarest but most dangerous subtype is vascular EDS (vEDS), caused by mutations in COL3A1 and associated with life-threatening arterial, intestinal, and uterine rupture.

Hypermobile EDS: The Most Common Presentation

hEDS is characterised by generalised joint hypermobility, recurring joint instability (subluxations and dislocations), musculoskeletal pain, and often significant fatigue. Accompanying features commonly include autonomic dysfunction — particularly postural orthostatic tachycardia syndrome (POTS), which produces dizziness, tachycardia, and pre-syncope on standing — mast cell activation syndrome (MCAS), and functional gastrointestinal disorders. The co-occurrence of these conditions is thought to reflect the broad role of connective tissue in vascular, neural, and gastrointestinal function rather than coincidental comorbidity.

Musculoskeletal pain in hEDS is multifactorial. Joint instability produces recurrent microtrauma to periarticular structures. Compensatory muscle hypertonicity — developed to substitute for lax passive restraints — produces widespread muscular fatigue and trigger point formation. The accumulation of repeated subluxation events can produce osteoarthritic joint changes disproportionate to the patient's age. Central sensitisation is common, partly as a consequence of the high volume of nociceptive input from repeatedly unstable joints, and partly due to the overlapping neurobiological vulnerabilities that characterise the condition.

Manual Therapy in EDS: Special Considerations

EDS — particularly hEDS — is one of the most clinically nuanced presentations that manual therapists encounter. The tissue laxity that defines the condition simultaneously makes patients more vulnerable to certain interventions and more likely to benefit from targeted soft tissue work. Several principles guide effective clinical reasoning in this population.

Joint hypermobility is not protective — it is a source of injury. The clinical reflex to "mobilise" restricted movement must be abandoned in favour of a stability-focused framework. The primary therapeutic objective is reducing excessive motion through strengthening the muscular and proprioceptive systems that compensate for ligamentous laxity. High-velocity manipulative techniques are generally contraindicated.

Pressure tolerances are highly variable and often lower than typical. EDS patients frequently have heightened sensory sensitivity and lower pain thresholds — partly due to central sensitisation, partly due to the genuine mechanical vulnerability of hypermobile tissue. Treatment intensity should begin conservatively and be titrated based on post-treatment response.

Fatigue is a significant complicating factor. EDS-related fatigue is physiological rather than motivational, reflecting the substantial energy cost of constant neuromuscular compensation for joint instability. Exercise prescription and treatment intensity should account for this, prioritising consistency and load management over progressive overload in the acute phases.

Clinical note: Any EDS patient presenting with sudden severe abdominal pain, thoracic pain, or unexplained haemodynamic instability requires emergency assessment to exclude vascular EDS-associated arterial rupture — a rare but potentially fatal complication.

Exercise and Rehabilitation

Low-load, proprioceptively demanding exercise is the cornerstone of long-term management. The goal is to develop neuromuscular control and muscular endurance sufficient to provide dynamic joint stability across the range of daily activities. Evidence supports Pilates-based exercise, hydrotherapy, and progressive resistance training (beginning with machine-based exercises that provide external joint support before progressing to free-weight activities that demand greater intrinsic stability).

Proprioceptive training — balance board work, single-leg stance progressions, perturbation training — directly addresses the proprioceptive deficit that accompanies ligamentous laxity and contributes significantly to the injury and subluxation cycle. Orthotics, bracing, and splinting may provide useful adjunctive stability support, particularly during activity transitions or high-demand periods.

References & Further Reading

  1. Malfait F, et al. The 2017 International Classification of the Ehlers-Danlos Syndromes. Am J Med Genet C. 2017;175(1):8–26.
  2. Castori M, et al. Management of pain and fatigue in the joint hypermobility syndrome (a.k.a. Ehlers-Danlos syndrome, hypermobility type). Orphanet J Rare Dis. 2012;7(1):48.
  3. Russek LN, et al. Presentation and physical therapy management of upper extremity hypermobility in patients with generalized joint hypermobility. J Hand Ther. 2016;29(2):175–188.
  4. Palmer S, et al. Exercise therapy for the management of musculoskeletal conditions in joint hypermobility syndrome. BMC Musculoskelet Disord. 2014;15(1):34.