What is the diagnostic approach and management for Ehlers-Danlos Syndrome (EDS)?

From the Guidelines

The diagnostic approach for Ehlers-Danlos Syndrome (EDS) should include genetic testing, particularly for the vascular type, as it can help identify defects in type III collagen, encoded by the COL3A1 gene, which is crucial for preventing fatal complications 1. The diagnosis of EDS begins with a clinical evaluation, assessing joint hypermobility using the Beighton score, skin hyperextensibility, and family history.

• Key aspects of diagnosis include:
  • Clinical evaluation
  • Genetic testing for vascular EDS
  • Assessment of joint hypermobility and skin hyperextensibility
• Management of EDS is primarily supportive and preventive, focusing on:
  • Physical therapy with gentle strengthening exercises to stabilize joints without overextension
  • Pain management using acetaminophen or NSAIDs as first-line treatments
  • Cardiovascular monitoring for those with vascular EDS
  • Patient education about avoiding joint hyperextension and using proper body mechanics
  • Regular follow-up with specialists, including rheumatologists, cardiologists, and geneticists Genetic testing is essential for confirming most EDS subtypes, particularly the more serious vascular type, and can help guide management and prevention of complications 1. For patients with hypermobile EDS, management may include low-resistance exercise, physical therapy for myofascial release, and pain management with a pain management specialist 1.
• Additional considerations for management include:
  • Avoiding high-impact activities and contact sports
  • Using braces or orthotics to support unstable joints
  • Considering low-dose opioids for acute pain management
  • Monitoring for and preventing complications like joint dislocations, skin fragility issues, and vascular complications.

From the Research

Diagnostic Approach for Ehlers-Danlos Syndrome (EDS)

• The diagnosis of EDS is based on clinical assessment and phenotype-guided genetic testing 2.
• The 2017 EDS classification criteria are used to establish an EDS diagnosis, and molecular genetic testing is used to confirm the diagnosis 2.
• Different molecular genetic tests can be performed, including EDS panel, microarray, whole exome sequencing (WES), single gene sequencing, familial variant testing, and other genetic panels 2.

Genetic Testing for EDS

• Genetic testing can confirm the diagnosis of EDS in patients who meet the clinical criteria, with a detection rate of approximately 83% 2.
• Genetic testing can also identify patients who do not fully meet the clinical criteria but have a positive molecular genetic diagnosis of EDS, with a detection rate of approximately 22% 2.
• The most common genes involved in EDS are COL5A1 and COL5A2, which are associated with classic EDS 3, 4.
• Other genes, such as COL3A1, may also be involved in EDS, particularly in patients with vascular EDS 5.
• Hypermobile EDS (hEDS) is unlikely to represent a single gene disorder and cannot be diagnosed by genetic investigations 6.

Management of EDS

• The management of EDS depends on the specific subtype and the severity of the symptoms.
• Patients with EDS require regular monitoring and follow-up to prevent and manage complications, such as joint dislocations and skin fragility.
• Genetic counseling is also important for patients with EDS, particularly those with a family history of the condition 3, 5.
• A less defensive approach to pregnancy and delivery may be required for patients with EDS, particularly those with a history of pregnancy complications 5.

EDS Subtypes and Genetic Associations

• Classic EDS (cEDS) is associated with mutations in COL5A1 and COL5A2 genes 3, 4.
• Vascular EDS (vEDS) is associated with mutations in COL3A1 gene 5.
• Hypermobile EDS (hEDS) is unlikely to represent a single gene disorder and cannot be diagnosed by genetic investigations 6.