From the Guidelines
Diagnosing Ehlers-Danlos Syndrome (EDS), particularly the vascular type (vEDS), requires identification of a causal COL3A1 variant, which is a crucial step due to its severe and life-threatening vascular complications. The diagnosis of vEDS involves a combination of clinical evaluation, family history assessment, and genetic testing to identify pathogenic variants in the COL3A1 gene, which encodes the pro-alpha1 chains of type III procollagen 1. Key aspects of the diagnosis include:
- Clinical presentation and natural history, with complications often starting during adolescence and repeating at unpredictable intervals
- Identification of characteristic signs such as arterial dissections, aneurysms, arterial ruptures, and arteriovenous fistulas
- Assessment of family history, as vEDS is an autosomal dominant disease with a significant risk of recurrence
- Genetic testing to confirm the diagnosis by identifying specific COL3A1 variants, with null variants showing a better outcome 1
- Evaluation of the patient's medical history, including symptoms like chronic pain, frequent dislocations, digestive issues, and cardiovascular problems
- Use of diagnostic criteria, such as the Beighton score, to assess joint hypermobility, although this is more relevant to other types of EDS
- Referral to specialists familiar with EDS, such as geneticists or rheumatologists, due to the complexity and frequent misdiagnosis of the condition.
From the Research
Diagnostic Criteria for Ehlers-Danlos Syndrome
To diagnose Ehlers-Danlos syndrome (EDS), several factors need to be considered, including:
- Joint hypermobility, which can be assessed using the Beighton score 2
- Skin hyperextensibility and/or fragility
- Generalized tissue fragility
- Family history of the condition
Clinical Assessment
A thorough clinical assessment is essential in the diagnostic process, including:
- Medical history
- Family history
- Physical examination 3
- Assessment of joint hyperlaxity using the Beighton score, with a score of 5 or more indicating generalized joint hypermobility in adults 2
Genetic Testing
Genetic testing, such as gene panel testing with massively parallel sequencing, can confirm the diagnosis of monogenic EDS types 3
- Molecular testing can identify the causative mutation in the majority of patients with classical EDS 4
- Genetic testing can aid in the diagnosis and management of EDS, as well as inform genetic counseling and family screening 5
Diagnostic Challenges
Diagnosing EDS can be challenging due to:
- Variable presentation of the condition
- Overlap with other conditions, such as joint hypermobility syndrome
- Lack of specific etiological treatment for EDS 2
- Need for a combination of clinical assessment, genetic testing, and other investigations to confirm the diagnosis 5
Management and Referral
Patients with suspected EDS should be referred to a department of genetics, physical medicine and rehabilitation, or rheumatology to: