What are the diagnostic criteria and management options for Ehlers-Danlos syndrome?

Ehlers-Danlos Syndrome Diagnosis

Diagnosis of hypermobile EDS (hEDS) requires meeting all three major clinical criteria: Beighton score ≥5/9 for joint hypermobility, soft/velvety skin without fragility, and exclusion of alternative diagnoses through genetic testing, while other EDS subtypes require molecular confirmation of causative genetic variants. 1, 2

Diagnostic Approach by EDS Subtype

Hypermobile EDS (Most Common Subtype)

Major Diagnostic Criteria - ALL must be present: 1

• Joint hypermobility: Beighton scale score ≥5/9 points:

  • Passive dorsiflexion of fifth fingers >90° (1 point each side) 1
  • Passive thumb apposition to flexor forearm surface (1 point each side) 1
  • Elbow hyperextension >10° (1 point each side) 1
  • Knee hyperextension >10° (1 point each side) 1
  • Forward bend with palms flat on floor, knees extended (1 point) 1

• Skin characteristics: Soft or velvety texture with normal or slightly increased extensibility 1

• Absence of skin/soft tissue fragility (which would suggest other EDS subtypes) 1

Critical Exclusion Step: Genetic testing identified alternative diagnoses in 26.4% of patients who initially met clinical hEDS criteria, requiring distinct management strategies. 3 This underscores that criterion three—exclusion of alternative diagnoses through genetic testing—is essential despite hEDS having no identified genetic marker. 3

Supportive Minor Criteria (Not Sufficient Alone)

• Autosomal dominant family history without skin abnormalities 1
• Recurrent joint dislocations or subluxations 1
• Chronic joint or limb pain 1
• Easy bruising 1
• Functional bowel disorders (gastritis, irritable bowel syndrome) 1
• Neurally mediated hypotension or postural orthostatic tachycardia syndrome 1
• High narrow palate with dental crowding 1

All Other EDS Subtypes (Including Vascular EDS)

Definite diagnosis requires molecular confirmation with identification of causative genetic variants, as clinical overlap between subtypes and other connective tissue disorders is substantial. 2 The 2017 International Classification recognizes 13 EDS subtypes, each with distinct genetic mutations. 2

Required Diagnostic Evaluation

Initial Workup for All Suspected EDS Cases

• Physical examination: Document Beighton score, skin characteristics, and tissue fragility 1
• Family history: Three-generation pedigree focusing on joint hypermobility and connective tissue features 1
• Echocardiogram: Evaluate for aortic root dilatation (occurs in 25-33% of classic and hypermobility types) 1
• Dilated eye examination: Exclude Marfan syndrome 1
• Genetic testing: Essential to exclude alternative diagnoses even when hEDS criteria are met clinically 3

Vascular EDS-Specific Evaluation

• Baseline vascular imaging: Head to pelvis to evaluate entire aorta and branches using non-invasive methods (Doppler ultrasound, CT, or MRI) 4
• Genetic testing for COL3A1 mutations: Required for definitive diagnosis 4

Management Framework

Cardiovascular Surveillance

For normal aortic root size: 1

• Echocardiogram every 2-3 years until adult height reached 1
• Repeat if cardiovascular symptoms develop or major physical activity increase planned 1

For aortic root dilation: 1

• Echocardiogram every 6 months if diameter >4.5 cm in adults or growth rate >0.5 cm/year 1
• Annual echocardiogram if diameter <4.5 cm and growth <0.5 cm/year 1

Vascular EDS requires: Annual surveillance imaging for any dilated or dissected segments 4

Musculoskeletal Management

• Low-resistance exercise to improve joint stability through increased muscle tone 1
• Physical therapy for myofascial release to facilitate exercise participation 1
• Pain management specialist involvement is crucial for chronic pain (present in majority of patients and correlates with hypermobility severity, dislocations, and previous surgery) 1, 5

Gastrointestinal Management

• Proton pump inhibitors, H2-blockers, or sucralfate for gastritis and reflux 1
• Promotility agents for delayed gastric emptying 1
• Antispasmodics, antidiarrheals, and laxatives as needed for irritable bowel symptoms 1
• Diagnostic gastric motor function testing if comorbid POTS with chronic upper GI symptoms 4

Bone Health

• Calcium and vitamin D supplementation 1
• Low-impact weight-bearing exercise 1
• DXA scan if height loss >1 inch 1

Vascular EDS-Specific Management

• Celiprolol (beta-blocker with vasodilatory properties) recommended to reduce vascular morbidity, though lacks FDA approval in US 4
• Avoid invasive vascular procedures due to fatal complication risk 4
• Surgical interventions require meticulous technique with pledgeted sutures for anastomoses 4

Critical Pitfalls to Avoid

• Do not diagnose hEDS without genetic testing to exclude alternative diagnoses: 26.4% of clinically diagnosed cases had alternative genetic conditions requiring different management 3
• Avoid invasive diagnostic procedures in vascular EDS: Use non-invasive imaging exclusively due to fatal complication risk 4
• Do not escalate to invasive nutrition support in hEDS with pain-predominant presentation: Most hEDS patients have visceral hypersensitivity rather than true dysmotility 1
• Avoid opioid dependence for chronic pain management: Particularly problematic in patients with gastrointestinal manifestations 4
• Do not overlook associated conditions: Screen for POTS, mast cell activation disorder, and chronic urinary retention 1

Multidisciplinary Team Requirements

Essential specialists include cardiology, gastroenterology, physical medicine, genetics, clinical psychology, and liaison psychiatry given high rates of psychological distress and functional impairment. 4