Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: A Clinical Guide to Diagnosis and Rehabilitation

For many clinicians, patients with chronic pain, fatigue, or unexplained joint instability can feel like diagnostic puzzles. Symptoms fluctuate, overlap multiple systems, and rarely fit neatly within one diagnosis. Yet for many, these patterns trace back to connective-tissue dysfunction—most notably, Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders (HSD).

Complex, often misunderstood, and frequently underdiagnosed, these conditions demand an integrated approach that blends medical insight with functional rehabilitation.

In this article, we’ll explore how to recognize, evaluate, and manage EDS and HSD—from diagnostic challenges to evidence-based strategies for improving movement, stability, and quality of life.

Ehlers-Danlos syndrome (EDS)

Ehlers-Danlos syndromes are a group of heritable connective-tissue disorders caused by genetic variations that weaken collagen and other extracellular-matrix proteins. These molecular changes reduce connective-tissue strength and elasticity, leading to musculoskeletal, cardiovascular, neurological, and gastrointestinal manifestations.¹

According to the 2017 International Classification of Ehlers-Danlos Syndromes, thirteen distinct subtypes are recognized, each defined by specific genetic, biochemical, and clinical features. Despite these differences, all share three hallmark characteristics:

• Joint hypermobility: May be generalized or localized, often causing instability, recurrent sprains, or chronic pain.

• Skin hyperextensibility: The skin stretches beyond normal limits and may appear soft or velvety.

• Tissue fragility: Leads to easy bruising, poor wound healing, and atrophic scarring.

Because connective tissue supports every organ system, EDS presents as a multisystem disorder—requiring clinicians to evaluate beyond joint symptoms and adopt a coordinated, team-based approach.

Hypermobility spectrum disorders (HSD)

Hypermobility spectrum disorders are connective-tissue conditions characterized by joint hypermobility that results in pain, instability, and recurrent injury. Although no genetic marker has yet been identified, individuals with HSD frequently present with musculoskeletal and systemic symptoms similar to those with EDS,¹ including:

• Headaches and fatigue: Often linked to autonomic dysfunction or postural challenges.

• Autonomic symptoms: Dizziness, tachycardia, or temperature intolerance.

• Gastrointestinal dysmotility: Bloating, reflux, constipation, or nausea.

• Generalized pain and proprioceptive deficits: Leading to reduced endurance and functional stability.

Connecting EDS and HSD: Moving toward a spectrum-based diagnosis

Until recently, Ehlers-Danlos syndrome and hypermobility spectrum disorders were viewed as separate conditions. However, growing evidence now suggests they exist along a shared clinical spectrum of connective-tissue and autonomic dysfunction rather than as distinct entities.¹

Central to this overlap is hypermobile Ehlers-Danlos syndrome (hEDS)—the most common subtype of EDS and the one most often confused with HSD in clinical practice.

This conceptual shift began in 2017, when the International EDS Consortium introduced the term hypermobility spectrum disorders to describe individuals with symptomatic hypermobility who did not meet the refined diagnostic criteria for hEDS. Subsequent studies have shown that individuals diagnosed with HSD and those with hEDS experience comparable levels of chronic pain, dysautonomia, mast-cell activation, and gastrointestinal involvement—challenging the notion that HSD represents a milder condition.¹

Today, clinicians recognize that hEDS and HSD fall along a continuum requiring individualized assessment, targeted rehabilitation, and multidisciplinary care.

Common EDS subtypes and diagnostic considerations

Understanding this continuum also helps clarify how clinicians recognize and diagnose these conditions in practice. While thirteen EDS subtypes have been identified, a few are far more common in rehabilitation settings—and understanding their distinguishing features can guide accurate evaluation and management.

• Hypermobile EDS (hEDS): The most common subtype, representing 80 to 90 percent of EDS cases (approximately 1 in 5,000 individuals).² Because its genetic basis remains unknown, diagnosis relies entirely on clinical criteria. Patients often present with joint instability, chronic pain, fatigue, and autonomic symptoms.

• Classical EDS (cEDS): The second most common subtype, occurring in roughly 1 in 20,000 individuals. It is characterized by skin fragility, atrophic scarring, and joint hypermobility—features that can significantly impact wound healing and daily function.³

• Vascular EDS (vEDS): The rarest but most life-threatening subtype. Caused by COL3A1 mutations, vEDS predisposes patients to arterial and organ rupture, with a median life expectancy of 46 years for males and 54 years for females.⁴

Clinical evaluation and diagnostic criteria

Diagnosing EDS and HSD requires balancing clinical judgment with objective criteria. Because symptom overlap is common, a structured, multidisciplinary approach helps ensure accuracy and early intervention.

When assessing patients with suspected EDS or HSD, you may rely on a combination of clinical judgment, physical examination, and genetic testing to guide evaluation. For 12 of the 13 EDS subtypes, molecular causes allow confirmation through genetic testing.¹ However, hypermobile EDS (hEDS) and HSD remain clinically defined, as no single gene has yet been identified.

The 2017 diagnostic framework for hEDS requires:

• Generalized joint hypermobility, measured using the Beighton score (age- and sex-adjusted).

• Systemic features or family history, such as soft or velvety skin, mild hyperextensibility, hernias, or pelvic-floor prolapse.

• Exclusion of other connective-tissue disorders, such as Marfan syndrome, Loeys–Dietz syndrome, or autoimmune disease.⁵

While the Beighton score objectively measures joint laxity, diagnostic delays are common, averaging 11 to 12 years before confirmation.¹

Common co-occurring conditions

Because connective tissue is present throughout the body, EDS and HSD often involve the autonomic, immune, and gastrointestinal systems. Among the most common coexisting conditions are postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS), both of which contribute to fatigue, pain, and reduced function.

Postural orthostatic tachycardia syndrome (POTS)

POTS is an autonomic nervous system dysfunction affecting blood flow regulation and is among the most frequent comorbidities seen in patients with hEDS or HSD.¹

When moving from lying to standing, patients experience an excessive heart rate increase (typically more than 30 beats per minute within 10 minutes) without a significant drop in blood pressure. This leads to hallmark symptoms such as:¹

• Orthostatic intolerance (dizziness, lightheadedness, or fainting)

• Cognitive changes (“brain fog,” poor concentration, fatigue)

• Cardiovascular responses (tachycardia, palpitations)

• Sleep disturbance or exercise intolerance

Patients reporting dizziness, fatigue, or faintness during positional changes should be screened for orthostatic intolerance. Compression garments, hydration, and graded exercise can reduce symptoms.

Mast cell activation syndrome (MCAS)

MCAS is an immune-regulation disorder characterized by inappropriate release of mast-cell mediators such as histamine, prostaglandins, and cytokines.¹

Symptoms can be multisystemic and unpredictable:⁶

• Dermatologic (flushing, itching, hives)

• Cardiovascular (hypotension, tachycardia, lightheadedness)

• Neurological (headache, anxiety, cognitive fog)

• Gastrointestinal (bloating, reflux, abdominal pain, nausea, altered bowel habits)

Because MCAS often presents with vague, fluctuating symptoms, clinicians should look for triggers such as stress, temperature, or food sensitivities and consider collaboration with allergy, immunology, or gastrointestinal specialists for management.

Rehabilitation strategies and clinical management

While there is no cure for EDS or HSD, evidence-based rehabilitation can help improve function, stability, and quality of life. In your practice, you can emphasize gradual, low-load progressions that build control and body awareness rather than aggressive strengthening or stretching. This patient-centered approach supports sustainable improvements and reduces the risk of flare-ups.

1. Foundational principles of care

Effective management begins with conservative, team-based intervention tailored to each patient’s presentation.

• Prioritize conservative treatment: Because of tissue fragility and delayed wound healing, all nonsurgical options should be exhausted before surgery.¹

• Address systemic contributors: Optimal outcomes depend on managing coexisting conditions such as neurological inflammation, dysautonomia, or MCAS.⁷

• Educate and support: Provide instruction on posture, body mechanics, and pacing. Bracing should match activity level and begin at the feet and pelvis to promote alignment; limit hard cervical collars to prevent weakness.⁸

Clinical insight: Empowering patients through education—especially around pacing, breathing, and gentle stabilization—often leads to more sustainable gains than external supports alone.

2. Movement retraining and biomechanical stabilization

For patients with EDS and HSD, movement retraining begins with restoring alignment and stability. Because joint laxity and muscle compensation often disrupt postural control, early rehabilitation focuses on rebuilding foundational mechanics.

Finding Functional Foundations model 

The Finding Functional Foundations (FFF) model provides a structured framework for retraining alignment, proprioception, and neuromuscular control through low-load, neuroplasticity-based exercise.

Core concepts of the FFF model include:⁸

• Distal-to-local strategy: For highly irritable patients or those with upper-cervical instability (UCI), begin at the core and pelvis to establish foundational postural control.

• Core and pelvic stability: Teach patients to find and maintain a neutral pelvis, often described as the “level-bucket” position, using pressure biofeedback and diaphragmatic breathing.

• Progressive integration: Once alignment is established, retraining expands to the trunk, shoulder girdle, and cervical region for full kinetic-chain coordination.

Diaphragmatic and respiratory correction

Dysfunctional breathing can impair pressure regulation and postural stability. Corrective strategies enhance deep-core activation and spinal alignment.

Common techniques include:⁹

• 90-90 diaphragmatic breathing: In hook-lying (hips and knees at 90°), engages hamstrings and diaphragm while reducing rib flare.

• 90-90 breathing with hip adduction/internal rotation: Coordinates pelvic-floor, diaphragm, and transverse-abdominis activation.

• Resisted-exhale breathing: Exhaling slowly through a straw or kazoo improves glottic control and pressure regulation.

Proprioceptive and alignment training

Because ligamentous laxity impairs joint position sense, proprioceptive retraining enhances motor control and confidence in movement.

Effective strategies include:

• Head laser training: Biofeedback is used to maintain neutral head alignment during trunk or limb movement.⁸

• “Drawing with the nose”: Controlled head-tracing movements to strengthen deep cervical stabilizers and improve fine motor precision.¹⁰

• Targeted alignment exercises: Supine Hamstring Inhibition, which gently lengthens overactive hamstrings to reduce lumbar hyperlordosis, and Supine Latissimus Dorsi Inhibition, which uses slow exhalations with arms overhead to release tension and improve rib–abdominal mechanics.⁹ 

Clinical insight: Encourage low-load, high-frequency practice—small, consistent corrective movements yield better results than aggressive stretching or strengthening.

Strength training 

For individuals with hEDS, building strength is crucial for stabilizing loose joints and managing pain. However, the process requires a slower, more controlled approach than traditional strength training, with a primary focus on stability and control.

General guidelines for strength training:

• Prioritizes stability over flexibility: Because hypermobility is characteristic of hEDS, the main objective of training is not to push toward end-range movements, but to strengthen and enhance stability at mid and end-range movements. Exercises should be designed to control movement and stabilize around the joints.

• Execute movements slowly and with control: Deliberate, slow movements are essential for engaging the deep stabilizing muscles that are needed to control joint position. Avoid high-speed or ballistic movements when initiating a strength program. Individuals may be able to work up to these types of movements, but they can exacerbate symptoms related to joint laxity.

• Utilize optimal resistance volumes: For some movements, opting for light weights, resistance bands, or even just body weight can minimize strain on the joints. For other movements, increased resistance may be helpful as proprioceptive feedback, particularly for isometric efforts. 

• Emphasize neuroplasticity: Focus on improving proprioception—the body's awareness of its position and movement—to rebuild the brain's connection to the body.

3. Advanced and systemic interventions

As patients progress, treatment may incorporate advanced neurological or systemic techniques to stabilize the autonomic system, reduce inflammation, and improve overall function.

Neurological integration and upper cervical control

The upper-cervical spine plays a critical role in postural orientation. For patients with upper cervical instability, interventions should emphasize neuromotor retraining rather than manipulation:¹⁰

• Eye-movement (“steering C1”) training: Guided visual tracking to facilitate subtle C1 repositioning while stabilizing C2.

• Tongue engagement: Pressing the tongue to the palate activates deep cervical stabilizers and improves jaw–hyoid–cervical alignment.

• Hyoid release: Gentle manual fascial work reduces tension around the hyoid and improves airway mechanics.

Neurological and autonomic stabilization

Low-intensity, system-based interventions can help regulate inflammation and pain:⁷

• Manual neurological work: Craniosacral therapy, visceral manipulation, or fascial counterstrain to restore mobility and reduce neural tension.

• Vagal nerve stimulation (VNS): Noninvasive stimulation to enhance parasympathetic tone and autonomic balance.

• Frequency-specific microcurrent (FSM) or neurofeedback: May help reduce neural hyperarousal and improve symptom modulation.

Systemic and multidisciplinary management

Because EDS and HSD frequently coexist with gastrointestinal, immune, or vascular dysfunction, coordinated care across disciplines is essential:⁶

• Dietary and GI management: Individualized nutrition (low-histamine, gluten-free, or low-FODMAP diets), smaller and more frequent meals, and adequate hydration support gut–brain regulation.

• Immune and mast-cell stabilization: Vitamin C, quercetin, and curcumin may reduce histamine release; medical providers may add antihistamines or cromolyn sodium.

• Abdominal vascular compression syndromes: Focus on core retraining and postural correction before surgical consideration; collaborate with vascular and GI specialists as needed.

Clinical application and takeaways

Ehlers-Danlos syndromes and hypermobility spectrum disorders challenge clinicians to think beyond isolated symptoms and approach care through an integrated, system-wide lens. By combining biomechanical retraining, autonomic regulation, and patient education, you can help patients reduce pain, restore confidence in movement, and improve quality of life.

Because every presentation is unique, progress often occurs gradually. Setting realistic goals and maintaining long-term adherence are key. A multidisciplinary, evidence-based approach ensures that patients receive care as comprehensive as the conditions themselves.

References

1. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Committee on Selected Heritable Disorders of Connective Tissue and Disability. (2022, July 8). Ehlers-Danlos syndromes and hypermobility spectrum disorders. In R. A. Wedge, T. Cartaxo, C. M. Spicer, et al. (Eds.), Selected Heritable Disorders of Connective Tissue and Disability. National Academies Press. https://www.ncbi.nlm.nih.gov/books/NBK584966/

2. Tinkle B, Castori M, Berglund B, Cohen H, Grahame R, Kazkaz H, Levy H. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):48-69. https://pubmed.ncbi.nlm.nih.gov/28145611/

3. Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):8-26. https://pubmed.ncbi.nlm.nih.gov/28306229/

4. Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genet Med. 2014 Dec;16(12):881-8. https://pubmed.ncbi.nlm.nih.gov/24922459/

5. Ehlers-Danlos Society. (2017, May). hEDS diagnostic criteria checklist [PDF]. https://www.ehlers-danlos.com/wp-content/uploads/2017/05/hEDS-Dx-Criteria-checklist-1.pdf

6. Stott, P., & Morris, A. (n.d.). Presentation of GI and abdominal comorbidities of HSD/EDS [Online course]. Medbridge. https://www.medbridge.com/educate/courses/presentation-of-gi-and-abdominal-comorbidities-of-hsd-eds-patricia-stott-amy-morris

7. Stott, P. (n.d.). Advanced cranial and upper cervical instability presentation in HSD/EDS [Online course]. Medbridge. https://www.medbridge.com/educate/courses/advanced-cranial-and-upper-cervical-instability-presentation-in-hsd-eds-patricia-stott

8. Stott, P., & Chalela, S. (2025). Advanced upper cervical supportive strategies with HSD/EDS [Online course]. Medbridge. https://www.medbridge.com/courses/details/advanced-upper-cervical-supportive-strategies-with-hsd-eds-patricia-stott-susan-chalela

9. Stott, P., & Morris, A. (n.d.). Abdominal vascular compression syndromes in HSD/EDS: Treatment paradigm [Online course]. Medbridge. https://www.medbridge.com/courses/details/abdominal-vascular-compression-syndromes-in-hsd-eds-treatment-paradigm-patricia-stott-amy-morris

10. Stott, P., & Chalela, S. (n.d.). Advanced upper cervical instability direct interventions in HSD/EDS [Online course]. Medbridge. https://www.medbridge.com/educate/courses/advanced-upper-cervical-instability-direct-interventions-in-hsd-eds-patricia-stott-susan-chalela