What are the main diagnostic criteria for Ehlers-Danlos Syndrome (EDS)?

Diagnostic Criteria for Ehlers-Danlos Syndrome (EDS)

The main diagnostic criteria for Ehlers-Danlos Syndrome (EDS) include generalized joint hypermobility assessed using the Beighton scale, skin hyperextensibility, tissue fragility, and specific clinical manifestations that vary by subtype, with confirmation through targeted genetic testing for all subtypes except hypermobile EDS (hEDS), which remains a clinical diagnosis. 1, 2

Classification and General Diagnostic Approach

The 2017 International Classification of Ehlers-Danlos Syndromes recognizes 13 subtypes, each with specific diagnostic criteria 2. The diagnostic process involves:

1. Clinical evaluation for characteristic features
2. Assessment of joint hypermobility using the Beighton scale
3. Targeted genetic testing based on suspected subtype
4. Exclusion of alternative diagnoses

Beighton Scale for Joint Hypermobility

The Beighton scale is a key assessment tool for joint hypermobility 1:

Criteria	Description	Points
Passive extension of little fingers	Beyond 90 degrees	1 point each side
Passive apposition of thumbs to forearm	Thumb touches forearm	1 point each side
Hyperextension of elbows	Beyond 10 degrees	1 point each side
Hyperextension of knees	Beyond 10 degrees	1 point each side
Forward flexion of trunk with knees extended	Palms flat on floor	1 point
Total possible score		9 points

A score of ≥5 indicates generalized joint hypermobility, which is a key diagnostic feature of EDS 1.

Specific Diagnostic Criteria by Common EDS Subtypes

1. Hypermobile EDS (hEDS) - Most Common (80-90% of cases)

Diagnosis requires meeting all three criteria 1, 2:

1. Generalized joint hypermobility (Beighton score ≥5)
2. Two or more of the following systemic manifestations:
   • Soft or velvety skin
   • Mild skin hyperextensibility
   • Unexplained striae
   • Bilateral piezogenic papules of the heel
   • Recurrent or multiple abdominal hernias
   • Atrophic scarring at multiple sites
   • Pelvic floor, rectal, and/or uterine prolapse
   • Dental crowding and high or narrow palate
   • Arachnodactyly
   • Arm span-to-height ratio ≥1.05
   • Mitral valve prolapse
   • Aortic root dilatation
3. Absence of unusual skin fragility AND exclusion of alternative diagnoses

2. Classical EDS

Diagnosis requires 1, 2:

• Major criteria:
  • Skin hyperextensibility and atrophic scarring
  • Generalized joint hypermobility
• Confirmatory molecular testing (COL5A1, COL5A2 genes)

3. Vascular EDS (vEDS)

Diagnosis requires 1, 3:

• Major criteria:
  • Family history of vEDS
  • Arterial rupture at a young age
  • Spontaneous sigmoid colon perforation
  • Uterine rupture during pregnancy
  • Carotid-cavernous sinus fistula
• Confirmatory molecular testing (COL3A1 gene)

Importance of Genetic Testing

Genetic testing is essential for definitive diagnosis of all EDS subtypes except hypermobile EDS 1, 4:

• Targeted genetic testing based on suspected subtype is recommended
• For vascular EDS: COL3A1 gene
• For classical EDS: COL5A1, COL5A2 genes
• For kyphoscoliotic EDS: PLOD1, FKBP14 genes
• For arthrochalasia EDS: COL1A1, COL1A2 genes

Recent research highlights that genetic testing identified alternative or additional diagnoses in 26.4% of patients initially diagnosed with hEDS, emphasizing the importance of genetic evaluation 4.

Clinical Features to Assess

During evaluation, assess for 1, 5:

• Skin findings:

  • Hyperextensibility
  • Soft or velvety texture
  • Tissue fragility and poor wound healing
  • Atrophic scarring
  • Easy bruising
  • Translucent skin with visible veins (particularly in vascular EDS)

• Musculoskeletal findings:

  • Joint hypermobility (Beighton scale)
  • Chronic musculoskeletal pain
  • Joint dislocations
  • Scoliosis (present in 19% of patients)

• Cardiovascular findings:

  • Valve prolapse (found in 43% of patients)
  • Arterial tortuosity
  • Aortic root dilatation
  • Risk of arterial dissection or rupture (particularly in vascular EDS)

Important Clinical Considerations

• Avoid invasive diagnostic procedures such as conventional angiography in vascular EDS patients due to high risk of complications 1
• Non-invasive imaging should be used whenever possible to minimize risk of arterial injury 1
• Bone mineral density assessment is important as osteoporosis is common 5
• Echocardiographic monitoring of aortic size and valvular condition is recommended 5
• Medical genetics consultation is recommended if a systemic arteriopathy or hereditary connective tissue disorder is suspected 1

Diagnostic Pitfalls to Avoid

• Overlooking alternative diagnoses: Recent research shows 26.4% of patients initially diagnosed with hEDS had alternative genetic diagnoses 4
• Relying solely on joint hypermobility: Hypermobility can be a shared phenotype across multiple disorders 4
• Failing to recognize serious subtypes: Vascular EDS can lead to life-threatening arterial ruptures with median survival of only 48 years 1
• Missing associated conditions: Assess for related conditions like Postural Orthostatic Tachycardia Syndrome (POTS) and Mast Cell Activation Syndrome (MCAS) 1