What are the clinical criteria for diagnosing Ehlers-Danlos Syndrome (EDS)?

Clinical Criteria for Diagnosing Ehlers-Danlos Syndrome (EDS)

The diagnosis of Ehlers-Danlos Syndrome requires meeting specific clinical criteria that vary by subtype, with hypermobile EDS requiring joint hypermobility (Beighton score ≥5), soft/velvety skin with normal or slightly increased extensibility, and absence of skin fragility. 1

Hypermobile EDS (hEDS) Diagnostic Criteria

Major Criteria (All Required)

1. Joint hypermobility confirmed by a Beighton score of 5 or more out of 9 points:
   • 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 fully extended (1 point)
2. Soft or velvety skin with normal or slightly increased extensibility
3. Absence of skin or soft tissue fragility (which would suggest other EDS subtypes) 1

Minor/Supportive Criteria

• Autosomal dominant family history with similar features
• Recurrent joint dislocations or subluxations
• Chronic joint or limb pain
• Easy bruising
• Functional bowel disorders (gastritis, irritable bowel syndrome)
• Neurally mediated hypotension or postural orthostatic tachycardia
• High, narrow palate
• Dental crowding 1

Vascular EDS Diagnostic Criteria

Vascular EDS is characterized by:

• Easy bruising
• Thin skin with visible veins
• Characteristic facial features
• Risk of arterial, intestinal, or uterine rupture
• Diagnosis confirmed by identifying defects in type III collagen (COL3A1 gene) 1

Classical EDS

Classical EDS presents with:

• Skin hyperextensibility
• Joint hypermobility
• Tissue fragility
• Poor wound healing
• Atrophic scarring 2

Diagnostic Evaluation

Required Testing

1. Physical examination focusing on joint mobility, skin characteristics, and systemic features
2. Family history assessment
3. Echocardiogram to evaluate for aortic root dilatation (occurs in 25-33% of classic and hypermobile EDS)
4. Dilated eye exam to exclude Marfan syndrome 1

Genetic Testing

• Most EDS subtypes can be confirmed by genetic testing except for hypermobile EDS
• EDS genetic panels have shown 75% diagnostic yield in patients meeting clinical criteria 3
• Whole exome sequencing may be necessary in complex cases

Differential Diagnosis

Important conditions to distinguish from EDS include:

• Marfan syndrome (has ectopia lentis, more significant aortic involvement)
• Loeys-Dietz syndrome (has arterial tortuosity, bifid uvula/cleft palate)
• Joint hypermobility spectrum disorders
• Osteogenesis imperfecta 4

Common Pitfalls in Diagnosis

1. Overlooking cardiovascular complications: Aortic root dilation occurs in 25-33% of classic and hypermobile EDS patients, requiring regular echocardiographic monitoring 1

2. Failing to recognize vascular EDS: This is the most dangerous subtype with risk of arterial dissection and rupture, with median survival of only 48 years 1

3. Misdiagnosing hypermobile EDS: The most common subtype, but requires excluding other conditions and meeting all major criteria

4. Inadequate follow-up: Patients with EDS require multisystem monitoring, including bone density assessment as osteoporosis is common 5

5. Incomplete genetic evaluation: While hypermobile EDS lacks a specific genetic test, other subtypes can be confirmed through genetic testing, which should be pursued when clinical criteria are met 3

By following these diagnostic criteria and avoiding common pitfalls, clinicians can accurately diagnose EDS and implement appropriate management strategies to prevent complications and improve quality of life.