What is the workup for Ehlers-Danlos syndrome?

Workup for Ehlers-Danlos Syndrome

The diagnostic workup for Ehlers-Danlos syndrome (EDS) requires a systematic clinical evaluation focusing on joint hypermobility, skin characteristics, and cardiovascular assessment, followed by appropriate genetic testing based on the suspected EDS subtype.

Clinical Evaluation

Joint Assessment

• Evaluate joint hypermobility using the 9-point Beighton scale:
  • 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)
  • Placing palms flat on floor with knees extended (1 point)
  • Score ≥5 indicates joint hypermobility 1

Skin Examination

• Assess for:
  • Skin hyperextensibility
  • Soft or velvety texture
  • Thin or translucent skin (especially in vascular EDS)
  • Easy bruising
  • Abnormal scarring
  • Striae 1

Cardiovascular Assessment

• Echocardiogram to evaluate:
  • Aortic root dimensions (dilatation occurs in 25-33% of classic and hypermobile EDS)
  • Mitral valve prolapse
  • Other structural abnormalities 1
• Consider MRI angiography or CT of entire aorta in suspected vascular EDS or if aortic dilatation is present 1

Additional Clinical Features

• Assess for:
  • Recurrent joint dislocations/subluxations
  • Chronic joint/limb pain
  • Functional bowel disorders
  • High, narrow palate
  • Dental crowding
  • Postural orthostatic tachycardia 1

Diagnostic Testing

Genetic Testing

• Hypermobile EDS (hEDS): No specific genetic test available; diagnosis based on clinical criteria 1, 2
• Classical EDS: COL5A1 and COL5A2 gene sequencing 2
• Vascular EDS: COL3A1 gene sequencing (highest priority due to risk of arterial rupture) 1, 2
• Other EDS subtypes: Specific gene testing based on clinical presentation 2

Imaging Studies

• Echocardiogram: Baseline for all patients, then follow-up based on findings:
  • Normal aortic root: Repeat every 2-3 years until adult height reached
  • Aortic root dilatation: Every 6 months if diameter >4.5 cm or rate of increase >0.5 cm/year; annually if <4.5 cm and rate of increase <0.5 cm/year 1
• Bone density scan (DXA) if height loss >1 inch 1
• Consider MRI angiography from cerebrovascular circulation to pelvis in suspected vascular EDS 1

Subtype-Specific Considerations

Hypermobile EDS

• Most common subtype
• Diagnosis requires all major criteria:
  1. Joint hypermobility (Beighton score ≥5)
  2. Soft/velvety skin with normal or slightly increased extensibility
  3. Absence of skin/soft tissue fragility 1
• Supported by minor criteria (family history, recurrent dislocations, chronic pain, etc.) 1

Vascular EDS

• Most serious form with risk of arterial rupture
• Characterized by thin skin with visible veins, characteristic facial features
• Median survival only 48 years
• Noninvasive vascular imaging preferred due to risk of complications with invasive procedures 1
• Pregnancy carries significant risks 1

Management Considerations

Cardiovascular Monitoring

• Regular echocardiograms based on findings
• Consider beta-blocker therapy for aortic root dilatation
• Surgical repair if:
  • Aortic measurements >4.5 cm
  • Rate of increase >1 cm/year
  • Progressive aortic regurgitation 1

Bone Health

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

Gastrointestinal Issues

• Consider proton pump inhibitors for gastritis and reflux 1

Common Pitfalls in Diagnosis

• Misdiagnosis: EDS is often misdiagnosed or diagnosis is delayed due to symptom overlap with other conditions 3, 4
• Overdiagnosis: While EDS is commonly suspected due to chronic pain complaints, true prevalence is estimated at only 1/10,000 4
• Incomplete evaluation: Failing to assess for cardiovascular complications can lead to missed opportunities for preventive management 5
• Inadequate genetic testing: Testing should be targeted based on clinical presentation rather than using broad panels 2

Special Considerations

• Pregnancy: Women with vascular EDS have increased risk of uterine rupture and vessel rupture during delivery; requires close monitoring 1
• Surgery: Tissue fragility may complicate surgical repair; careful tissue handling and pledgeted sutures recommended for vascular EDS 1
• Osteoporosis: Studies show high prevalence of osteoporosis in EDS patients, emphasizing importance of bone density assessment 5

Remember that a definitive diagnosis is crucial for proper management and prevention of life-threatening complications, particularly in vascular EDS where arterial rupture is a major concern.