Is there a blood test to confirm Ehlers-Danlos Syndrome (EDS)?

Blood Testing for Ehlers-Danlos Syndrome

There is no blood test that can confirm hypermobile Ehlers-Danlos syndrome (hEDS), which accounts for 80-90% of all EDS cases, as the genetic cause remains unknown and diagnosis is entirely clinical. 1, 2 However, for other EDS subtypes, genetic testing on blood samples can provide molecular confirmation.

Genetic Testing by EDS Subtype

Vascular EDS (Type IV) - Blood Test Available

• COL3A1 gene mutation testing is the definitive diagnostic test and should be performed urgently when this life-threatening subtype is suspected 1, 2
• This is the most critical blood test to obtain, as vascular EDS carries significant mortality risk from arterial or organ rupture 1
• Fibroblast culture demonstrating structurally abnormal collagen type III can provide supportive evidence if genetic testing is inconclusive 1

Classical EDS (Types I and II) - Blood Test Available

• COL5A1 or COL5A2 gene mutation testing provides molecular confirmation 1
• Genetic testing confirmed diagnosis in 75% of patients who met clinical criteria in one pediatric study 3

Hypermobile EDS - No Blood Test Available

• No causative genes have been identified, making genetic testing futile 1, 2
• Diagnosis relies entirely on clinical criteria including the Beighton score (≥5/9 points for adults under 50 years) 2, 4
• Routine genetic testing for hEDS is explicitly not recommended 1

Recommended Testing Strategy

Multi-Gene Panel Approach

• Multi-gene panel testing covering COL3A1, COL5A1, COL5A2, TGFBR1, TGFBR2, PLOD1, and other arteriopathy genes is the most efficient diagnostic approach when EDS is suspected but the subtype is unclear 1
• EDS panel testing confirmed molecular diagnosis in 28% of patients who did not fully meet clinical criteria in one study 3
• Avoid routine whole-genome or exome sequencing in suspected hEDS, as it provides no diagnostic value 1

Essential Screening Blood Tests Before Genetic Testing

While these don't confirm EDS, they help assess complications and guide management:

• Complete blood count (CBC) with differential to evaluate for cytopenias or eosinophilia 1
• Comprehensive metabolic panel including liver and renal function 1
• Baseline serum tryptase level if symptoms suggest mast cell activation syndrome (flushing, urticaria, wheezing) 1
• Vitamin B12 level, which is characteristically elevated in myeloproliferative variants of EDS with arteriopathy 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for inflammatory assessment 1
• Quantitative immunoglobulin levels including IgE if allergic symptoms are present 1

Critical Pitfalls to Avoid

• Do not order genetic testing for hEDS - it wastes resources and provides no diagnostic information 1
• Do not delay COL3A1 testing when vascular EDS is suspected - this is a medical emergency requiring urgent molecular confirmation 1
• Do not perform routine mast cell activation syndrome testing in all hEDS patients with isolated GI symptoms - only test when systemic symptoms suggest generalized mast cell disorder 1
• Recognize that mutation identification may fail even when protein analysis confirms a collagen defect, as only coding sequences are investigated 1

When to Refer for Genetic Testing

Refer to medical genetics specialists when:

• Clinical features suggest EDS and you need guidance on which genetic test to order 1
• Family history shows autosomal dominant inheritance pattern 1
• Arteriopathy is suspected requiring comprehensive gene panel 1
• Genetic counseling is paramount before mutation screening due to complex financial, insurance, familial, and social implications 1