Classical Ehlers-Danlos Syndrome: Diagnostic Criteria, Genetic Confirmation, and Management

What are the criteria for cEDS?

Classical Ehlers-Danlos Syndrome (cEDS) is diagnosed primarily through specific clinical criteria, including hallmark features like significant skin hyperextensibility and characteristic atrophic scarring, often complemented by generalized joint hypermobility and supported by genetic testing.

Understanding Classical Ehlers-Danlos Syndrome (cEDS)

Classical Ehlers-Danlos Syndrome (cEDS) is a rare, inherited connective tissue disorder primarily affecting the skin, joints, and blood vessels. It is one of the more common types within the Ehlers-Danlos Syndromes (EDS) group, which are characterized by defects in collagen synthesis or processing. In cEDS, the underlying genetic cause is typically a mutation in the COL5A1 or COL5A2 genes, which code for type V collagen, or, less commonly, the COL1A1 gene. These genetic alterations lead to structural and functional abnormalities in collagen, impacting the integrity and elasticity of connective tissues throughout the body.

The 2017 International Classification for cEDS Diagnosis

The diagnosis of cEDS is predominantly clinical, based on a set of major and minor criteria established by the 2017 International Classification for Ehlers-Danlos Syndromes. These criteria help clinicians differentiate cEDS from other EDS types and other connective tissue disorders.

Major Criteria

The presence of these two major criteria is highly indicative of cEDS:

• Skin Hyperextensibility: This refers to the ability of the skin to stretch significantly beyond what is considered normal, often returning slowly to its original position after release. It is typically assessed by gently pulling the skin on the forearm, neck, or abdomen.
• Atrophic Scarring: Characteristic "cigarette paper" or "papyraceous" scars are a hallmark. These are thin, wide, wrinkled, and often hyperpigmented or hypopigmented scars that result from even minor trauma or surgical incisions. They are particularly noticeable over pressure points like the knees, shins, elbows, and forehead.

Minor Criteria

While less specific on their own, the presence of multiple minor criteria supports a cEDS diagnosis, especially if only one major criterion is met:

• Generalized Joint Hypermobility (GJH): Assessed using the Beighton Score, cEDS typically presents with mild to moderate joint hypermobility, unlike the more pronounced hypermobility seen in hypermobile EDS (hEDS). This can manifest as recurrent joint subluxations or dislocations (especially patellar, shoulder, or temporomandibular joint).
• Smooth, Velvety Skin: The skin often feels unusually soft and doughy to the touch.
• Molluscoid Pseudotumors: These are fleshy, tumor-like lesions, often found over pressure points (e.g., elbows, knees), resulting from the calcification of herniated fat.
• Subcutaneous Spheroids: Small, firm, mobile nodules that can be palpated under the skin, usually on the forearms and shins. They are thought to be cysts containing fat.
• Complications of Joint Hypermobility: Including sprains, dislocations/subluxations, and pain.
• Muscle Hypotonia and/or Delayed Gross Motor Development: Especially noticeable in infancy and early childhood.
• Easy Bruising: Due to fragile blood vessels.
• Hernia: Such as umbilical or hiatal hernias, due to weakened connective tissue.
• Epicanthal Folds: Folds of skin over the inner corner of the eye.
• Rectal Prolapse: Can occur in childhood.
• Family History: A positive family history of cEDS or similar symptoms.

Diagnostic Requirements for cEDS

According to the 2017 classification, a definitive diagnosis of cEDS requires:

1. Presence of both major criteria: Skin hyperextensibility and atrophic scarring. OR
2. Presence of one major criterion AND at least three minor criteria.

Genetic Confirmation

While the clinical criteria are paramount, genetic testing plays a crucial role in confirming the diagnosis and differentiating cEDS from other EDS types.

• Confirmation: Identification of a pathogenic variant in COL5A1, COL5A2, or rarely, COL1A1, confirms the clinical diagnosis.
• Exclusion: A negative genetic test for these genes in an individual meeting clinical criteria might prompt consideration of other EDS types or other connective tissue disorders. However, it's important to note that a small percentage of clinically diagnosed cEDS cases may not have an identified genetic mutation in these genes.

Differential Diagnosis and Considerations

Given the overlap in symptoms with other connective tissue disorders, a thorough differential diagnosis is essential. Conditions such as hypermobile EDS (hEDS), vascular EDS (vEDS), kyphoscoliotic EDS (kEDS), and even other disorders like Marfan Syndrome or Loeys-Dietz Syndrome, must be considered and ruled out where appropriate. The specific constellation of skin, joint, and scar features is key to distinguishing cEDS.

Implications for Exercise and Management

For individuals diagnosed with cEDS, understanding these criteria is vital not only for diagnosis but also for guiding appropriate management and exercise strategies. As an Expert Fitness Educator, I emphasize the following:

• Multidisciplinary Approach: Management of cEDS requires a team approach, often involving geneticists, dermatologists, rheumatologists, physical therapists, and occupational therapists.
• Joint Protection: Due to joint hypermobility and fragility, activities that put excessive stress on joints should be modified or avoided. Focus on low-impact exercises.
• Strength and Stability: Strengthening muscles around joints can help improve stability and reduce the risk of subluxations and dislocations. However, this must be done cautiously, avoiding end-range joint movements that could overstretch ligaments.
• Proprioception and Balance: Exercises that improve body awareness and balance are beneficial for preventing falls and injuries.
• Skin Care: Special attention to skin care is needed to prevent wounds and manage existing scars. Sun protection is crucial for scar integrity.
• Listen to Your Body: Individuals with cEDS must be acutely aware of their body's signals, avoiding pain and overexertion. Exercise should always prioritize safety and functional improvement over intensity or performance metrics.
• Physical Therapy: A physical therapist experienced in hypermobility disorders can design a safe and effective exercise program tailored to individual needs, focusing on core stability, gentle strengthening, and pain management.

Conclusion

The diagnosis of Classical Ehlers-Danlos Syndrome hinges on a precise evaluation of clinical features, primarily significant skin hyperextensibility and characteristic atrophic scarring, supported by other minor criteria and ideally, genetic confirmation. For fitness professionals and enthusiasts, recognizing these criteria is fundamental to understanding the unique physical challenges faced by individuals with cEDS, enabling tailored, safe, and effective exercise interventions that promote well-being while minimizing risk. Early and accurate diagnosis is key to implementing appropriate management strategies and improving quality of life.