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

From the Guidelines

Testing for Ehlers-Danlos syndrome, particularly the vascular type, should always involve genetic testing to identify pathogenic variants in the COL3A1 gene, as this is a requirement for diagnosis and crucial for predicting prognosis and guiding management. The diagnostic process for Ehlers-Danlos syndrome (EDS) involves a combination of clinical evaluation, family history assessment, and genetic testing. For vascular EDS (vEDS), which is the most severe form due to its life-threatening vascular complications, identification of a causal COL3A1 variant is essential 1. This type of EDS is characterized by a disruption in the assembly of type III collagen fibrils, leading to a significant loss of mechanical strength in arteries and other hollow organs.

Key Considerations for Testing

• Genetic testing is critical for diagnosing vEDS and should be performed under the guidance of a geneticist or specialist familiar with connective tissue disorders.
• The test involves a blood sample and can take several weeks for results.
• Skin biopsies may occasionally be used to examine collagen structure, but genetic testing is the primary method for diagnosing vEDS.
• The Beighton score, which measures joint hypermobility, may be used as part of the clinical assessment for other types of EDS but is not directly relevant to the diagnosis of vEDS.

Importance of Early Identification

Early identification of vEDS is crucial due to its severe vascular complications, which can start during adolescence and recur at unpredictable intervals 1. The most common complications involve medium-sized arteries, including dissections, aneurysms, arterial ruptures, and arteriovenous fistulas. Aortic dissection can occur without dilatation, and the rate of recurrence of organic complications in patients with vEDS is significant, with 1.6 events per 5-year period 1. Life expectancy is reduced, averaging 51 years, which underscores the importance of prompt diagnosis and management.

Management and Monitoring

Proper diagnosis allows for appropriate management strategies and monitoring for potential complications specific to vEDS. This includes close monitoring during pregnancy and delivery, as women with vEDS are at risk of increased bruising, hernias, varicosities, and rupture of large blood vessels 1. Postpartum hemorrhage may be severe, and incisions heal slowly, suggesting the use of retention sutures. Given the high risk of vascular complications, patients with vEDS should be managed by a multidisciplinary team including cardiologists, geneticists, and obstetricians, especially during pregnancy.

From the Research

Ehlers-Danlos Syndrome Testing

• Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders characterized by hyperextensible skin, hypermobile joints, easy bruisability, and fragility of the connective tissues 2.
• The diagnosis of EDS is based on clinical assessment and phenotype-guided genetic testing, with most EDS subtypes being confirmed by genetic testing except for hypermobile EDS 2, 3.
• Molecular genetic testing can be used in combination with the 2017 clinical diagnostic criteria to establish an EDS diagnosis in children, with a correlation between generalized joint hypermobility, poor healing, easy bruising, atrophic scars, skin hyperextensibility, and developmental dysplasia of the hip with a positive molecular result 2.
• Different molecular genetic tests can be performed, including EDS panel, microarray, whole exome sequencing, single gene sequencing, familial variant testing, and other genetic panels 2.
• Skin biopsy with electron microscopy can be helpful in the decision process of whether and when to perform genetic testing 4.
• Accurate diagnosis of EDS is important for correct multidisciplinary management and is associated with better clinical outcomes for patients 5.

Types of Ehlers-Danlos Syndrome

• There are 13 recognized EDS subtypes, with a wide degree of symptom overlap among subtypes and with other connective tissue disorders 5.
• Fourteen different types of EDS are recognized, of which the molecular cause is known for 13 types, caused by variants in 20 different genes 3.
• The hypermobile type of EDS has unknown molecular underpinnings 3.

Diagnosis and Management

• Management of EDS consists of a care team responsible for surveillance of major and organ-specific complications, integrated physical medicine and rehabilitation 3.
• No specific medical or genetic therapies are available for any type of EDS, and treatment modalities have variable success 6.
• Occupational therapy and bracing have been shown to be effective options for symptom relief, while neuropathic modulators are the least well tolerated 6.