What is the blood test for Ehlers-Danlos syndrome?

Blood Tests for Ehlers-Danlos Syndrome

For Ehlers-Danlos syndrome (EDS), the primary diagnostic blood test is genetic testing for specific gene mutations, with the particular genes tested depending on the suspected EDS subtype.

Genetic Testing Based on EDS Subtype

• For vascular EDS (type IV), testing for mutations in the COL3A1 gene is essential for definitive diagnosis 1
• For classical EDS, genetic testing focuses on COL5A1 and COL5A2 genes, with COL1A1 also being relevant in some cases 2
• For hypermobile EDS (hEDS), which accounts for 80-90% of EDS cases, no specific genetic marker has been identified, making diagnosis primarily clinical rather than through blood testing 1

Diagnostic Process

• Medical geneticists are the primary specialists who diagnose and classify EDS, as they have expertise in evaluating inherited connective tissue disorders 1
• The diagnostic approach includes:
  • Clinical assessment of joint hypermobility using the Beighton scale 1
  • Skin assessment for hyperextensibility, fragility, and scarring 1
  • Family history assessment for autosomal dominant inheritance pattern 1
  • Genetic testing when appropriate based on suspected subtype 3

Laboratory Diagnosis Methods

• Laboratory diagnosis of EDS is based on three main approaches:
  1. Demonstration of structurally abnormal collagen type III by fibroblasts 3
  2. Identification of mutations in specific genes (e.g., COL3A1, COL5A1, COL5A2) 3
  3. Linkage analysis with intragenic polymorphic markers 3

Genetic Testing Considerations

• Mutation identification can be challenging as mutations are "private" (unique to families) and widely distributed throughout large genes 3
• Next-generation sequencing (NGS) with appropriate multigene panels shows great potential for diagnosing EDS 2
• In a study of 72 pediatric patients, molecular genetic testing confirmed EDS in 83% of patients who met clinical criteria 4
• For suspected vascular EDS, genetic testing should be performed at a referral center with experience in genetically mediated arteriopathies 3

Important Caveats and Limitations

• Genetic testing may fail to identify mutations in some cases, as only the coding sequence and closely surrounding regions are typically investigated 3
• Mutations within genes like COL3A1 are not specific to one EDS type, as they can be found in multiple EDS subtypes 3
• No clear phenotype-genotype correlations have been identified, meaning the mutation does not predict disease type, course, or severity 3
• Genetic heterogeneity exists, with some patients showing normal collagen III metabolism despite having clinical features of EDS 3
• For hypermobile EDS, which is the most common subtype, diagnosis remains clinical as no specific genetic markers have been identified 1

When to Consider Genetic Testing

• When clinical features strongly suggest a specific EDS subtype 1
• When there is a family history of EDS or unexplained arterial dissections 3
• When planning pregnancy in cases of suspected vascular EDS, as this information can guide risk assessment 3
• When evaluating patients with aortic dissection or aneurysm at young age 3