Clinical Symptoms and Diagnostic Approach for Ehlers-Danlos Syndrome
The diagnostic approach for Ehlers-Danlos Syndrome (EDS) requires thorough evaluation of multiple systems including cardiovascular, gastrointestinal, and musculoskeletal, with hypermobile EDS (hEDS) being the most common subtype characterized primarily by joint hypermobility and tissue fragility.
Major Clinical Symptoms
Joint Manifestations
- Generalized joint hypermobility assessed using the 9-point Beighton scale (score ≥5 indicates hypermobility) 1
- Recurrent joint dislocations or subluxations 1, 2
- Chronic joint or limb pain 1, 3
Skin Manifestations
- Soft or velvety skin with normal or slightly increased extensibility 1
- Skin hyperextensibility (more pronounced in classical EDS than hypermobile EDS) 4
- Abnormal scarring with formation of atrophic scars 4
- Easy bruising 1, 4
Gastrointestinal Manifestations
- Functional bowel disorders (functional gastritis, irritable bowel syndrome) 1
- Gastroparesis and abnormal gastric emptying (more common than in general population) 1
- Abdominal pain, particularly postprandial pain 1
- Nausea and vomiting 1
Cardiovascular Manifestations
- Aortic root dilation (occurs in 25-33% of individuals with classic and hypermobile EDS) 1
- Mitral valve prolapse 1
- Orthostatic intolerance and Postural Orthostatic Tachycardia Syndrome (POTS) 1, 2
Other Clinical Features
- High, narrow palate and dental crowding 1
- Neurally mediated hypotension 1
- Chronic fatigue 3
- Anxiety disorders 1, 3
- Pelvic and bladder dysfunction 3
Diagnostic Approach
Step 1: Clinical Evaluation
- Apply the 2017 diagnostic criteria for hypermobile EDS 3
- Assess joint hypermobility using the Beighton scale:
- Passive dorsiflexion of fifth fingers >90° (1 point each side)
- Passive apposition of thumbs to flexor surface of forearm (1 point each side)
- Hyperextension of elbows >10° (1 point each side)
- Hyperextension of knees >10° (1 point each side)
- Forward flexion with palms flat on floor with knees extended (1 point) 1
- Evaluate skin for hyperextensibility, fragility, and scarring 4
- Document family history of similar features 1
Step 2: Cardiovascular Assessment
- Perform baseline echocardiogram to evaluate for aortic root dilatation 1, 2
- For normal aortic root size: repeat echocardiogram every 2-3 years until adult height reached 1
- For aortic root dilation: echocardiogram every 6 months if diameter >4.5 cm or rate of increase >0.5 cm/year 1
- Consider magnetic resonance angiography of the entire aorta in young adulthood 1
Step 3: Gastrointestinal Evaluation
- For patients with chronic upper GI symptoms and comorbid POTS, consider diagnostic testing of gastric motor functions 1
- Consider testing for celiac disease earlier in the diagnostic evaluation (not only in those with diarrhea) 1
- For lower GI symptoms, consider anorectal manometry, balloon expulsion test, or defecography due to high prevalence of pelvic floor dysfunction 1
Step 4: Genetic Testing
- Genetic testing is recommended for definitive diagnosis, particularly for vascular EDS (COL3A1) 2, 5
- Note that hypermobile EDS currently has no identified genetic mutation to help with diagnosis 3
Step 5: Differential Diagnosis
- Rule out other EDS subtypes (classical, vascular, kyphoscoliotic, arthrochalasia, dermatosparaxis) 6
- Consider other connective tissue disorders such as Marfan syndrome (evaluate with dilated eye exam) 1
- Differentiate between EDS and Exercise-Induced Laryngeal Dysfunction (EILD) which can mimic EDS symptoms 1
Management Principles
- Avoid invasive procedures when possible in vascular EDS patients due to risk of fatal complications 5
- Avoid opioid use for chronic pain management, especially in patients with gastrointestinal manifestations 1, 5
- Implement physical and occupational therapy to reduce joint instability and pain 7, 3
- Consider brain-gut behavioral therapies for psychological support 1, 5
- For POTS symptoms, consider increasing fluid and salt intake, exercise training, and compression garments 2
- For gastrointestinal symptoms, treat based on predominant symptoms (antiemetics for nausea, antispasmodics for pain) 1
Common Pitfalls
- Misdiagnosis due to overlapping symptoms with other connective tissue disorders 6
- Underestimation of prevalence (estimated at 1/10,000) 7
- Failure to recognize milder variants of EDS which may be more common than previously thought 8
- Overlooking extra-articular symptoms such as anxiety disorders, chronic pain, and functional GI disorders 3