Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders

Original Editor - Jess Bell Top Contributors - Jess Bell, Kim Jackson, Stacy Schiurring, Tarina van der Stockt, Naomi O'Reilly, Lucinda hampton, Vidya Acharya, Olajumoke Ogunleye and Ewa Jaraczewska

Introduction

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a heritable connective tissue disorder characterised by joint hypermobility, skin involvement, and widespread multisystem manifestations that significantly impact rehabilitation outcomes. The 2017 International EDS Consortium classification fundamentally transformed diagnostic practice by establishing strict criteria for hEDS diagnosis while simultaneously introducing Hypermobility Spectrum Disorders (HSD) for individuals with symptomatic hypermobility who do not meet the full hEDS criteria.

This reclassification replaced the previously used terms "Joint Hypermobility Syndrome (JHS)" and "Benign Joint Hypermobility Syndrome," recognising that these conditions exist on a clinical spectrum and are far from benign in their impact on patient function and quality of life.  The 2017 criteria emphasise the importance of comprehensive assessment beyond joint mobility alone, requiring rehabilitation professionals to adopt a holistic, multisystem approach to evaluation and management while recognising that these are research criteria still undergoing validation in clinical practice.

Epidemiology and Prevalence

Collectively, hEDS and HSD affect an estimated 1 in 300-500 individuals, making these conditions considerably more common than previously recognised and amongst the most prevalent connective tissue disorders encountered in clinical practice. Recent population-based studies suggest the combined diagnosed prevalence may be as high as 1 in 500 people, with expert consensus indicating that HSD is particularly common and likely underdiagnosed in many healthcare settings. These conditions demonstrate a pronounced female predominance, with 70% of individuals with hEDS being female and 30% male.  Women with these conditions are generally diagnosed nine years later than men.

Joint hypermobility itself follows a predictable age-related decline: with general population studies showing hypermobility prevalence of 64.6% in children aged 4–7, declining to 35.6% at age 10, and 9.4% in those aged 12–13 years.  While symptomatic hypermobility typically manifests differently across age groups and may be underrecognised in older adults whose historical hypermobility is no longer apparent on examination.

Ethnic variation is also significant, with higher rates of joint hypermobility documented in individuals of South Asian, African, and Middle Eastern heritage compared to Northern European populations, though comprehensive epidemiological data for hEDS and HSD across different ethnic groups remains limited.

The hEDS-HSD Spectrum: Understanding Diagnostic Boundaries

The relationship between hEDS and HSD represents a diagnostic spectrum rather than distinct clinical entities, with substantial overlap in presentation, symptoms, and functional impact that directly influences rehabilitation planning. It should be noted that asymptomatic hypermobility is not a pathology or medical diagnosis but rather a normal variation of mobility; patients who present with asymptomatic hypermobility benefit from skilled education on protective and preventive interventions to avoid future musculoskeletal injuries (e.g. musicians putting extra strain on their hands, or children who "W" sit). While the 2017 International Consortium created separate diagnostic categories to facilitate research and improve clinical precision, recent evidence confirms significant clinical similarities between the conditions, with cluster analysis demonstrating overlapping manifestations that challenge the notion of clear diagnostic boundaries. For rehabilitation professionals, this overlap is clinically relevant as both conditions present with comparable patterns of joint instability, chronic pain, fatigue, and exercise intolerance.

The following 4-minute optional video overviews the differences between hEDS and HSD.

The 2017 diagnostic criteria for hEDS require systematic evaluation across three domains. To establish a diagnosis, an individual must fulfil all three domains: demonstrating generalised joint hypermobility (Domain 1), meeting at least two of three specific criteria related to clinical features and family history (Domain 2), and excluding other heritable connective tissue disorders (Domain 3). This structured approach aims to improve diagnostic specificity while ensuring clinically relevant cases are identified.

Table 1.0: The 2017 diagnostic criteria for hED according to the International EDS Consortium classification

Criterion	Requirements
Criterion 1:generalised joint hypermobility	Assessed using the Beighton score (score ≥5 for pubertal adults up to age 50) Passive dorsiflexion of fifth metacarpophalangeal (MCP) joint ≥90° (1 point per hand) Passive apposition of thumb to flexor aspect of forearm (1 point per hand) Hyperextension of elbow ≥10° (1 point per arm) Hyperextension of knee ≥10° (1 point per leg) Forward flexion of trunk with knees extended and palms flat on floor (1 point)
Criterion 2:two or more of features A, B, or C must be present	Feature A: Systemic manifestations of a generalised connective tissue disorder (≥5 must be present) Unusually soft or velvety skin Mild skin hyperextensibility Unexplained striae distensae or rubrae (stretch marks) at back, groins, thighs, breasts, and/or abdomen in adolescents, men, or pre-pubertal women without a history of significant gain or loss of body fat or weight Bilateral piezogenic papules of the heel Recurrent or multiple abdominal hernias (umbilical, inguinal, or crural) Atrophic scarring involving at least two sites and without the formation of truly papyraceous and/or haemosideric scars Pelvic floor, rectal, and/or uterine prolapse in children, men, or nulliparous women without morbid obesity or other known predisposing medical condition Dental crowding and high or narrow palate Arachnodactyly (positive Steinberg/Walker-Murdoch wrist and thumb signs) Arm span-to-height ratio ≥1.05 Mitral valve prolapse (MVP) mild or greater based on echocardiographic criteria Aortic root dilatation with Z-score >+2 Feature B: Positive family history One or more first-degree relatives independently meeting the current diagnostic criteria for hEDS Feature C: Musculoskeletal complications (≥1 must be present) Musculoskeletal pain in two or more limbs, recurring daily for at least 3 months Chronic, widespread pain for ≥3 months Recurrent joint dislocations or frank joint instability, in the absence of trauma (≥3 atraumatic dislocations in the same joint or ≥2 atraumatic dislocations in two different joints occurring at different times) Three or more atraumatic dislocations in the same joint or two or more atraumatic dislocations in two different joints occurring at different times Medical confirmation of joint instability at two or more sites not related to trauma
CRITERION 3: all prerequisites must be met	Absence of unusual skin fragility - this should be a clear prerequisite that distinguishes hEDS from other EDS types Exclusion of other heritable and acquired connective tissue disorders, including: Other types of Ehlers-Danlos syndrome Loeys-Dietz syndrome Marfan syndrome Other collagenopathies Autoimmune rheumatological conditions (e.g., lupus, rheumatoid arthritis) Other conditions that could explain the symptoms

Link to a diagnostic checklist of hEDS

Table 2.0: Signs and symptoms of Hypermobile Ehlers-Danlos Syndrome versus Hypermobility Spectrum Disorders

Feature	hEDS	HSD	Practical Clinical Indicators
Joint Hypermobility	Beighton Score ≥6/9 (≤50 years) or ≥5/9 (>50 years)	May have Beighton Score <6/9 but with symptomatic hypermobility	Historical photos showing extreme flexibility; ability to perform 'party tricks' in youth Joint stiffness following periods of inactivity suggesting compensation for instability
Systemic Features	≥5/12 systemic manifestations required (skin hyperextensibility, atrophic scarring, piezogenic papules, recurrent hernias, dental crowding, high palate, etc.)	May have some systemic features but <5/12	Examine: skin texture on forearms; dental alignment; presence of unexplained scars Ask about hernias, pelvic organ prolapse, frequent dental work
Family History	First-degree relative meeting hEDS criteria	May have family history of hypermobility	Family members with 'double-jointedness'; unexplained chronic pain; early arthritis; frequent injuries; similar systemic symptoms
Musculoskeletal Complications	Specific complications: ≥3 recurrent dislocations same joint OR ≥2 dislocations different joints chronic widespread pain with structural abnormalities confirmed ligamentous laxity	Joint pain and minor trauma without major structural complications	Assess: frequency and pattern of dislocations; imaging findings; pain distribution; response to standard treatments; subluxation versus true dislocation history
Skin Features	Soft, velvety skin texture mild hyperextensibility (>1.5cm forearm skin lift) atrophic scarring	Variable skin features, may be soft but not meeting specific hEDS criteria	Test: Skin texture comparison with examiner's skin; measure forearm skin lift; examine scars for width and texture; assess bruising patterns
Functional Impact	Significant disability affecting multiple life domains frequent medical consultations work/education limitations	Moderate functional impact may be episodic generally maintains major life activities	Evaluate: Time off work/study; healthcare utilisation; ADL modifications; exercise tolerance; social participation changes
Pain Characteristics	Chronic, widespread, often neuropathic quality may be disproportionate to visible pathology	Localised or regional pain typically mechanical in nature proportionate response to activity	Document: Pain distribution maps; quality descriptors (burning, shooting vs aching); triggers and relief factors; sleep disruption patterns
Diagnostic Certainty	Meets all three 2017 criteria definitively	Does not meet full hEDS criteria but has symptomatic hypermobility requiring management	Clinical reasoning: Document which criteria are/aren't met; consider alternative diagnoses; plan for diagnostic review over time

It is important to note that symptom severity and functional impairment do not necessarily correlate with the diagnostic category; patients with HSD may experience equally debilitating symptoms as those with hEDS. Therefore it is important that rehabilitation professionals focus on functional assessment and symptom management rather than diagnostic labels, as treatment approaches for both conditions emphasise similar principles (e.g. joint protection, graduated strengthening, proprioceptive training, and multisystem symptom management).

Signs and Symptoms

The clinical presentation of hEDS and HSD encompasses a complex constellation of musculoskeletal, multisystem, and functional manifestations that significantly impact rehabilitation planning and outcomes.

The primary features include generalised joint hypermobility, joint instability, pain, soft and hyperextensible skin with atrophic scars and easy bruising, dental crowding, abdominal hernias, pelvic organ prolapse, marfanoid body habitus, mitral valve prolapse, and aortic root dilatation.

Joint-related symptoms are particularly relevant for rehabilitation professionals, with subluxations, dislocations, and soft tissue injuries occurring commonly, either spontaneously or with minimal trauma, and often being acutely painful. Chronic pain represents one of the most debilitating aspects of these conditions, distinct from acute injury-related pain and often requiring specialised pain management approaches alongside rehabilitation interventions.

Beyond musculoskeletal symptoms, patients frequently present with significant multisystem manifestations that profoundly influence exercise tolerance and rehabilitation capacity. Functional gastrointestinal disorders, Postural Orthostatic Tachycardia Syndrome (POTS), chronic pelvic pain, and psychological dysfunction are not only frequently observed in hEDS but often constitute the main reason patients pursue evaluation. Dysautonomia, particularly POTS, affects a substantial proportion of patients and presents with symptoms such as hypotension, orthostasis, dizziness, palpitations, exercise intolerance, and memory/concentration problems. This leads to not enough blood returning to the brain, which can be felt as lightheadedness, brain fog and fatigue, creating significant challenges for traditional exercise-based rehabilitation approaches.

Additional systemic features that rehabilitation professionals should recognise include skin fragility and hyperextensibility, hernias, varicose veins, dental crowding, and various ocular manifestations. Fatigue is a pervasive symptom that often limits functional capacity more than joint hypermobility itself, while sleep disturbances, temperature regulation difficulties, and gastrointestinal dysfunction can all impact rehabilitation tolerance and progress. .

Diagnosis

The Beighton Score and Five-Part Questionnaire on Hypermobility serve different but complementary purposes. The Five-Part Questionnaire on Hypermobility is valuable as an initial screening tool, particularly when clinical examination is impractical, while the Beighton Score provides objective confirmation and quantification of current joint hypermobility.  Current hEDS diagnostic criteria incorporate both tools: the Beighton Score assesses present hypermobility (Domain 1), while the Five-Part Questionnaire on Hypermobility can provide historical evidence when physical examination is compromised or when scores fall 1 point below the Beighton cut-off.

The Beighton Score of Hypermobility

The Beighton Score is a clinical assessment tool that objectively measures joint mobility at specific anatomical sites through standardised physical examination:

Components, scored bilaterally where applicable, include:

• Passive dorsiflexion of fifth metacarpophalangeal joint ≥90° (2 points)
• Passive apposition of thumb to flexor aspect of forearm (2 points)
• Passive hyperextension of elbow ≥10° (2 points)
• Passive hyperextension of knee ≥10° (2 points)
• Forward flexion of trunk with knees straight, palms flat on floor (1 point)

Scoring: Total range 0-9 points. Current diagnostic criteria for hypermobile Ehlers-Danlos syndrome use age-dependent cut-offs: ≥5/9 for adults aged 18-50 years; ≥4/9 for adults >50 years.

Link to the Beighton Score of Hypermobility assessment

Figure 1. Beighton Scale of Hypermobility

The scoring criteria changes based on age as people become stiffer over time:

1. Pre-pubertal girls and boys - a score of six or more is considered positive for joint hypermobility
2. Pubertal men and women up until the age of 50 years - a score of five or more is considered positive
3. Adults aged over 50 - a score over four is considered positive

It is important to remember when using this measure that the Beighton Score refers to pain associated with hypermobility - not hypermobility alone.

Five-Part Questionnaire on Hypermobility (5PQ)

The Five-Part Questionnaire on Hypermobility is a self-reported screening tool designed to identify generalised joint hypermobility through retrospective and current assessment of joint mobility. It comprises five yes/no questions addressing both present and historical hypermobility features:

1. Can you now (or could you ever) place your hands flat on the floor without bending your knees?
2. Can you now (or could you ever) bend your thumb to touch your forearm?
3. As a child, did you amuse your friends by contorting your body into strange shapes or could you do the splits?
4. As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?
5. Do you consider yourself double-jointed?

Scoring: Each positive response scores 1 point (total range 0-5). A score of ≥2 indicates probable generalised joint hypermobility.

Performance: The 5PQ demonstrates moderate correlation with clinical assessment (Beighton Score). Validation studies report sensitivity of 72-91% and specificity of 61-78%, with substantial to almost perfect test-retest reliability. Notably, the tool shows high negative predictive value (97-99%), making it particularly effective for ruling out individuals without generalised joint hypermobility, but lower positive predictive value (13-42%), resulting in a higher false-positive rate.

Link to the Five Part Questionnaire on Hypermobility

Differential Diagnoses

hEDS shares numerous clinical features with other conditions, making careful differential diagnosis essential for appropriate management. Among primary connective tissue disorders, classical EDS is distinguished by significant skin hyperextensibility and characteristic atrophic scarring, while vascular EDS presents with arterial fragility and distinctive facial features that differ from the hEDS phenotype. Marfan syndrome can be differentiated through the presence of aortic root dilatation, lens dislocation, and specific skeletal features outlined in the revised Ghent criteria. Loeys-Dietz syndrome typically presents with arterial tortuosity, bifid uvula, and hypertelorism that are not characteristic of hEDS.

Secondary hypermobility conditions also require consideration during the diagnostic process. Benign Joint Hypermobility Syndrome, while historically recognised as a separate entity, is now generally considered part of the hEDS spectrum. Down syndrome frequently presents with associated hypermobility but includes a characteristic phenotype that readily distinguishes it from hEDS. Osteogenesis imperfecta can be differentiated by the presence of bone fragility, blue sclerae, and hearing loss.

Several musculoskeletal conditions may present with overlapping symptoms that complicate diagnosis. Fibromyalgia typically presents with widespread pain but without the generalised joint hypermobility that characterises hEDS. Chronic fatigue syndrome predominantly features debilitating fatigue with minimal joint involvement, though fatigue is also common in hEDS patients. Postural orthostatic tachycardia syndrome (POTS) may coexist with hEDS, making differentiation particularly challenging and potentially requiring recognition of both conditions simultaneously.

Medical Treatment Options

Medical management plays a crucial supportive role in hEDS, primarily focusing on symptom control and managing comorbidities rather than addressing the underlying connective tissue disorder. While there is no cure for hEDS, appropriate medical interventions can significantly improve quality of life and functional capacity, creating a foundation for effective rehabilitation. Understanding these interventions helps rehabilitation professionals coordinate care, recognise when medical review is warranted, and optimise treatment timing and approaches.

Medical management in hEDS typically requires a multidisciplinary approach. Rehabilitation professionals should maintain communication with medical teams to optimise treatment outcomes and identify when medical review is necessary.

Table 3.0 Overview of Medical Interventions in hEDS

System	Common Manifestations	Medical Management	Rehabilitation Considerations
Cardiovascular	Orthostatic intolerance POTS Mitral valve prolapse	Fludrocortisone (volume expansion) Midodrine (vascular tone) Beta-blockers (heart rate control) Increased fluids/salt intake Compression garments Regular echocardiography monitoring	Monitor for exercise intolerance, postural symptoms, and cardiovascular response to activity
Gastrointestinal	Gastroparesis Chronic constipation Gastrooesophageal reflux	Prokinetic agents (domperidone, metoclopramide) Osmotic laxatives Dietary fibre modification Proton pump inhibitors/H2 antagonists	Consider timing of exercise relative to meals Abdominal/pelvic floor exercises may influence GI symptom
Pain	Neuropathic pain Musculoskeletal pain Chronic widespread pain	Gabapentin/pregabalin or tricyclic antidepressants (neuropathic) Topical NSAIDs (musculoskeletal) Multimodal approach Opioid avoidance where possible	Multimodal pain management supports active rehabilitation Be aware of medication side effects (drowsiness, dizziness)
Dermatological	Skin fragility Slow wound healing Excessive bruising	Protective dressings Gentle adhesives Nutritional support Specialised wound care protocols Assessment for bleeding disorders	Use caution with taping, orthoses, and manual techniques Monitor skin integrity during interventions

Rehabilitation Treatment Options

Rehabilitation management of hEDS requires careful consideration of the underlying tissue fragility and joint instability that characterise the condition. A multidisciplinary approach emphasising graded exercise, joint protection, and functional adaptation forms the cornerstone of effective management. Understanding the evidence base helps rehabilitation professionals deliver optimal care while recognising the limitations of current research in this evolving field.

Therapeutic exercise and motor function training have demonstrated efficacy in hEDS management, with improvements in pain and proprioception observed in programmes of 4-8 weeks duration. A knowledgeable therapist is essential, as some interventions may worsen symptoms if inappropriately implemented.

Table 4.0. Overview of Rehabilitation Interventions in hEDS

Intervention Area	Key Components	Evidence-Based Approaches	Clinical Considerations
Exercise Therapy	Strengthening Proprioceptive training Cardiovascular conditioning Core stabilisation Biomechanical correction Hydrotherapy (aquatic therapy)	Isometric strengthening as foundation Cautious progression to isotonic exercises Joint protection education: avoid end-range joint positions Low-impact activities preferred Balance and joint position sense training Deep stabilising muscle activation Graded exercise programmes (4-8 weeks minimum) Temperature-controlled aquatic therapy	Pain and proprioception show significant improvements with structured programmes Proprioceptive deficits are well-documented in hEDS, training improves joint stability and reduces injury risk Avoid ballistic or high-impact activities Monitor for post-exertional symptom exacerbation Hydrotherapy reduces gravitational loading
Occupational Therapy	Joint protection Assistive technology Workplace adaptation ADL training	Energy conservation techniques Activity modification strategies Orthotic and adaptive equipment prescription Ergonomic assessment Fatigue management and pacing	Focus on maintaining independence whilst minimising symptom exacerbation Workplace modifications can improve work sustainability
Orthotic Management	Ankle-foot orthoses (AFO) Knee bracing Spinal support Hand/wrist splints	Functional support during activities Enhanced proprioceptive feedback Activity-specific protection Night-time positioning Weaning protocols to prevent dependency	Careful selection required to balance stability with mobility Temporary use during acute episodes Prevent muscle weakening through over-reliance
Pain Management	Cognitive- behavioural approaches Pacing and energy conservation strategies Multimodal pain relief	Pain psychology services Activity grading Self-management strategies Integration with pharmacological management	Address both physical and psychological aspects Chronic pain is common and often neuropathic in nature Multidisciplinary approach essential
Nutritional Support	Gastrointestinal management Nutritional optimisation	Dietetic assessment Address malnutrition and deficiencies GI symptom management support	GI complications are common and can significantly impact rehabilitation outcomes if not addressed

Clinical Pearls: Key Principles for Exercise Prescription

Safe Progression:

• Start with isometric exercises in mid-range positions
• Progress gradually to controlled isotonic movements
• Avoid end-range loading and ballistic movements
• Regular monitoring of joint stability and symptom response
• Individualised progression based on tolerance

Exercise Cautions:

• Avoid high-impact and ballistic activities
• Monitor for delayed post-exertional symptom exacerbation
• Maintain careful joint position awareness
• Regular reassessment of exercise tolerance
• Consider cardiovascular autonomic dysfunction when prescribing aerobic exercise

Additional Resources

Clinical Resources:

The Ehlers-Danlos syndromes (EDS) GP Toolkit

The following resources include various games and exercises that may be useful for children with BJHS:

• PhysiFun Physical Fundamentals
• Hypermobility Exercises from Ashford and St Peter's Hospitals, NHS Foundation Trust
• Hypermobility exercises for under 5’s from the Royal Berkshire NHS Foundation Trust

Optional Additional Reading:

• Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M. The 2017 international classification of the Ehlers–Danlos syndromes. InAmerican Journal of Medical Genetics Part C: Seminars in Medical Genetics 2017 Mar (Vol. 175, No. 1, pp. 8-26).
• Ritelli M, Chiarelli N, Cinquina V, Vezzoli M, Venturini M, Colombi M. Looking back and beyond the 2017 diagnostic criteria for hypermobile Ehlers‐Danlos syndrome: A retrospective cross‐sectional study from an Italian reference center. American Journal of Medical Genetics Part A. 2024 Feb;194(2):174-94.