What are the typical presentations and management strategies for Ehler Danlos syndrome?

Ehlers-Danlos Syndrome: Presentation and Management

Ehlers-Danlos syndrome (EDS) is characterized by joint hypermobility, skin hyperextensibility, and tissue fragility, with 13 recognized subtypes requiring specific diagnostic criteria and management approaches tailored to prevent life-threatening complications. 1

Clinical Presentation

Major Diagnostic Features

• Joint hypermobility: Assessed using the 9-point Beighton scale (score ≥5 indicates hypermobility) 1
• Skin abnormalities:
  • Hyperextensibility
  • Soft or velvety texture
  • Thin or translucent appearance
  • Abnormal scarring
  • Easy bruising 1
• Tissue fragility: Affecting blood vessels, internal organs, and skin 1, 2

Minor Diagnostic Features

• Autosomal dominant family history
• 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 3

EDS Subtypes

EDS is clinically and genetically heterogeneous with 13 recognized subtypes 4:

1. Hypermobile EDS (hEDS):

   • Most common subtype
   • No specific genetic test available
   • Diagnosis based on clinical criteria 1

2. Classical EDS:

   • Mutations in collagen-encoding genes
   • Prominent skin hyperextensibility and scarring 4

3. Vascular EDS (vEDS):

   • Life-threatening subtype
   • Severe arterial and gastrointestinal fragility
   • Caused by mutations in COL3A1 gene
   • Presents with arterial tearing/dissection, colonic perforation, or visceral rupture before age 45 5

4. Other subtypes:

   • Include spondylodysplastic EDS and musculocontractural EDS (associated with glycosaminoglycan abnormalities) 6
   • Various genetic mutations affecting collagen structure or biosynthesis 4, 7

Diagnostic Evaluation

1. Clinical assessment:

   • Complete joint hypermobility evaluation using Beighton scale
   • Skin examination for characteristic features
   • Family history documentation 1

2. Genetic testing:

   • Targeted genetic testing based on clinical features
   • COL3A1 gene sequencing for suspected vascular EDS
   • Broader genetic panels if initial testing is negative but clinical suspicion remains high 1

3. Cardiovascular assessment:

   • Echocardiogram to evaluate aortic root dimensions
   • Assessment for mitral valve prolapse
   • Evaluation for aortic dilatation 1

Management Strategies

Cardiovascular Management

• Monitoring:
  • Normal aortic root: Echocardiogram every 2-3 years until adult height reached
  • Aortic root dilation: Echocardiogram every 6 months if diameter >4.5 cm or growth rate >0.5 cm/year 3, 1
• Surgical consideration:
  • Consider repair if aortic measurements >4.5 cm
  • Consider repair if growth rate >1 cm/year
  • Consider repair if progressive aortic regurgitation 1
  • Caution with invasive procedures due to tissue fragility, especially in vEDS 5

Musculoskeletal Management

• Low-resistance exercise to improve joint stability
• Physical therapy for myofascial release
• Pain management specialist involvement for chronic pain
• Bracing preferred over surgery when possible 3, 1
• Vitamin C supplementation as a cofactor for collagen cross-linking 3

Gastrointestinal Management

• Proton pump inhibitors, H-2 blockers, or sucralfate for gastritis and reflux
• Promotility agents for delayed gastric emptying
• Antispasmodics, antidiarrheals, and laxatives for irritable bowel symptoms 3, 1

Bone Health

• Calcium and vitamin D supplementation
• Low-impact weight-bearing exercise
• DXA scan for height loss >1 inch 3, 1

Pregnancy and Obstetric Care

• High-risk monitoring throughout pregnancy
• Increased risk of uterine and vessel rupture during delivery in vEDS
• Cesarean delivery often recommended for known vEDS patients 1

Lifestyle Modifications

• Education about minimizing injury risk
• Maintaining normal blood pressure
• Annual surveillance of vascular tree by ultrasound, CT, or MRI in vascular subtypes
• Consider celiprolol (beta blocker with vasodilatory properties) in vascular EDS 1, 5

Special Considerations for Vascular EDS

• Arteriography is contraindicated
• "Wait-and-see" approach with close surveillance preferable to unwarranted surgery
• Simple surgical procedures preferred over complex techniques
• Prolonged postoperative surveillance with close medical follow-up and serial CT scans 5

Early diagnosis and appropriate multidisciplinary management are crucial for improving outcomes and preventing life-threatening complications in patients with EDS.