What is the diagnostic workup for Ehlers-Danlos syndrome?

Diagnostic Workup for Ehlers-Danlos Syndrome

The diagnosis of Ehlers-Danlos Syndrome (EDS) requires a comprehensive clinical evaluation focused on joint hypermobility assessment using the Beighton scale, skin examination, family history, and targeted genetic testing based on the suspected EDS subtype. 1, 2

Initial Clinical Assessment

Joint Hypermobility Evaluation

• Apply the 9-point Beighton scale (score ≥5 indicates hypermobility):
  • Passive dorsiflexion of each fifth finger >90° (1 point each side)
  • Passive apposition of each thumb to flexor surface of forearm (1 point each side)
  • Hyperextension of each elbow >10° (1 point each side)
  • Hyperextension of each knee >10° (1 point each side)
  • Ability to place palms flat on floor with knees extended (1 point) 1

Skin Assessment

• Evaluate for:
  • Hyperextensibility
  • Soft or velvety texture
  • Fragility and poor wound healing
  • Atrophic scarring
  • Easy bruising 1, 3

Family History

• Document autosomal dominant inheritance pattern
• Identify affected family members with similar features 1

Secondary Clinical Features Assessment

• Recurrent joint dislocations or subluxations
• Chronic joint or limb pain
• Functional bowel disorders (gastritis, irritable bowel syndrome)
• Neurally mediated hypotension or postural orthostatic tachycardia
• High, narrow palate
• Dental crowding 1

Cardiovascular Assessment

• Echocardiogram to evaluate for:

  • Aortic root dilatation (occurs in 25-33% of classic and hypermobile EDS)
  • Valve abnormalities 1, 2, 4

• Complete vascular imaging:

  • CT or MRI from head to pelvis for suspected vascular EDS
  • Baseline assessment before pregnancy or surgical interventions 2

Genetic Testing

• Targeted genetic testing based on clinical presentation:
  • COL5A1 and COL5A2 for classic EDS (detects mutations in approximately 50% of cases) 5
  • COL3A1 for vascular EDS 2
  • TNXB for a subset of hypermobile EDS 1

Additional Evaluations

• Bone mineral density assessment (DXA scan)

  • Important as osteoporosis is common in EDS 1, 4

• Dilated eye examination (to exclude Marfan syndrome) 1

Diagnostic Algorithm

1. Clinical suspicion based on joint hypermobility, skin findings, and/or family history
2. Apply Beighton criteria for joint hypermobility (score ≥5 required)
3. Assess for major diagnostic criteria:
   • Joint hypermobility (Beighton score ≥5)
   • Soft/velvety skin with normal or slightly increased extensibility
   • Absence of skin/soft tissue fragility suggestive of other EDS subtypes
4. Evaluate for minor diagnostic criteria
5. Cardiovascular assessment with echocardiogram
6. Genetic testing based on suspected subtype
7. Rule out other connective tissue disorders (e.g., Marfan syndrome)

Clinical Pearls and Pitfalls

• EDS is clinically heterogeneous with 13 recognized subtypes, making precise diagnosis challenging 3
• Inter- and intrafamilial phenotypic variability is common, even with the same genetic mutation 5
• No single genetic test can diagnose all forms of EDS; testing should be guided by clinical presentation 2, 5
• Vascular EDS carries the highest mortality risk due to arterial rupture and requires more urgent diagnosis and management 2
• Avoid invasive procedures when possible due to tissue fragility 2
• Regular cardiovascular monitoring is essential, especially for those with aortic abnormalities 1, 2

By following this systematic approach to diagnosis, clinicians can identify patients with EDS and initiate appropriate multidisciplinary management to reduce morbidity and mortality associated with this condition.