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Ehlers-Danlos syndrome (classical)
Classical Ehlers-Danlos syndrome is a type of Ehlers-Danlos syndrome characterised by extremely stretchy skin, fragile skin that bruises easily, and hypermobile joints. It typically presents from birth and can affect people of all ages and backgrounds.
Overview
Classical Ehlers-Danlos syndrome (cEDS) is a hereditary condition that primarily affects connective tissues throughout the body. Connective tissue provides strength and elasticity to many parts of the body, including the skin, joints, and blood vessels. In cEDS, the connective tissue is weaker than usual, leading to symptoms such as skin that stretches easily, joints that move beyond the normal range, and fragile tissues [PMID:33675005].
This condition is one of the more common forms of Ehlers-Danlos syndrome, with an estimated prevalence of around 1 in 20,000 people. Symptoms are often noticeable from birth or early childhood. While cEDS can affect various body systems, it typically does not reduce life expectancy. Management focuses on addressing specific symptoms and preventing complications.
Symptoms & clinical features
The main symptoms of classical Ehlers-Danlos syndrome include significant skin hyperextensibility, which means the skin can be stretched much more than usual but returns to its normal position when released. Skin fragility is also common, leading to easy bruising, slow wound healing, and characteristic 'cigarette paper' scars, particularly over pressure points like the shins [PMID:33675005].
Joint hypermobility, especially in the smaller joints such as fingers and toes, is another key feature. This can result in joint instability, dislocations, and chronic pain. Other possible symptoms may include muscle weakness, easy bruising, and issues with healing after surgery. Dental problems, such as crowded teeth or gum fragility, can also occur.
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Affected organs
Classical Ehlers-Danlos syndrome predominantly affects organs rich in connective tissue. The skin is significantly impacted, leading to hyperextensibility, fragility, and impaired wound healing. The joints are also widely affected, with hypermobility leading to instability and potential dislocations.
Less commonly, other systems may be involved. For example, some individuals may experience issues with blood vessels, though severe vascular complications are rare in cEDS compared to other Ehlers-Danlos types. The eyes can sometimes show signs of increased fragility. Internal organ involvement is generally not a prominent feature of classical EDS, but careful consideration is given during medical procedures that might stress connective tissues.
Risks & severity
The severity of classical Ehlers-Danlos syndrome can vary considerably between individuals, even within the same family. While some people may experience mild symptoms, others might have more significant challenges due to joint instability, chronic pain, or frequent skin injuries [PMID:33675005].
Complications can include recurrent joint dislocations, chronic pain, and issues with wound healing that may require specific care. Although some forms of Ehlers-Danlos syndrome carry a risk of life-threatening vascular complications, these are generally not a prominent feature of cEDS. Life expectancy for individuals with classical EDS is typically not reduced.
Genetic causes
Classical Ehlers-Danlos syndrome is caused by pathogenic variants in genes responsible for producing type V collagen, a crucial component of connective tissue. The primary genes associated with cEDS are COL5A1 and COL5A2 [PMID:20301458]. These genes provide instructions for making components of type V collagen.
Type V collagen plays an important role in the structure and strength of connective tissues, helping to organise other collagen fibres. Pathogenic variants in COL5A1 or COL5A2 lead to either a reduced amount of functional type V collagen or the production of faulty collagen. This weakens the connective tissue, causing the characteristic features of cEDS, such as skin hyperextensibility and joint hypermobility.
- COL5A1 collagen type V alpha 1 chain
- COL5A2 collagen type V alpha 2 chain
Inheritance pattern
Classical Ehlers-Danlos syndrome is inherited in an autosomal dominant pattern. This means that a person only needs one copy of an altered gene (either COL5A1 or COL5A2) in each cell to develop the condition. In most cases, an affected individual inherits the altered gene from one affected parent.
Each child of an individual with cEDS has a 50% chance of inheriting the altered gene and therefore developing the condition. Sometimes, a new pathogenic variant can occur spontaneously in an individual who has no family history of the condition. In such cases, the affected individual can then pass the condition on to their children.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
A diagnosis of classical Ehlers-Danlos syndrome is often suspected based on an individual's clinical signs and symptoms, such as significant skin hyperextensibility and joint hypermobility. Specific diagnostic criteria have been developed to guide clinicians. Referral to a clinical geneticist or genetic counsellor is generally recommended for evaluation.
Confirmation of cEDS typically involves genetic testing, which looks for pathogenic variants in the COL5A1 and COL5A2 genes [PMID:33675005]. This testing can be accessed through the NHS Genomic Medicine Service, often following a referral from a specialist. The relevant NHS R-codes for testing Ehlers-Danlos syndrome, including classical type, would be discussed by the referring clinician.
Management & lifestyle
Management of classical Ehlers-Danlos syndrome focuses on symptom relief, preventing complications, and improving quality of life. This often involves a multidisciplinary team approach, including physiotherapists, occupational therapists, and pain management specialists. Physical therapy can help strengthen muscles around joints to improve stability and reduce dislocations.
Skin care is important due to fragility; gentle handling, protective padding, and careful wound management can help. Regular monitoring for complications and tailored advice for activities and lifestyle modifications are often provided. Genetic counselling is also a key part of management, offering information about inheritance patterns and support for affected individuals and their families. Always follow advice from your healthcare team; never stop or start any treatment without consulting a medical professional.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like classical Ehlers-Danlos syndrome are typically referred by their GP or another specialist to a clinical genetics service. These services are part of the NHS Genomic Medicine Service (GMS).
Clinical geneticists and genetic counsellors at these centres will assess symptoms, review family history, and can arrange appropriate genetic testing. The testing pathways are guided by national guidelines and use specific R-codes (e.g., R146, R246) which refer to panels for Ehlers-Danlos syndromes. Genetic counsellors play a vital role in providing information, support, and discussing the implications of a diagnosis for both the individual and their family.
Frequently asked questions
Is classical Ehlers-Danlos syndrome the same as hypermobile Ehlers-Danlos syndrome?
No, classical Ehlers-Danlos syndrome (cEDS) and hypermobile Ehlers-Danlos syndrome (hEDS) are distinct types. While both involve joint hypermobility, cEDS is primarily characterised by significant skin hyperextensibility and fragility, and is caused by pathogenic variants in COL5A1 or COL5A2. hEDS does not typically have these severe skin features and its genetic cause is still largely unknown.
Can classical Ehlers-Danlos syndrome be inherited from only one parent?
Yes, classical Ehlers-Danlos syndrome follows an autosomal dominant inheritance pattern. This means that if one parent has the condition, there is a 50% chance that each of their children will inherit the altered gene and therefore the condition.
Does classical Ehlers-Danlos syndrome affect life expectancy?
Generally, classical Ehlers-Danlos syndrome does not reduce life expectancy. While it can cause significant symptoms and require ongoing management, it is not typically associated with the severe internal organ or vascular complications seen in some other forms of Ehlers-Danlos syndrome.
What kind of exercise is safe for someone with classical Ehlers-Danlos syndrome?
It's important to consult with a physiotherapist experienced in connective tissue disorders. Low-impact activities that strengthen muscles and support joints, such as swimming, cycling, or tai chi, are often recommended. High-impact sports or activities that put excessive strain on joints may need to be avoided or modified to prevent injury.
How is classical Ehlers-Danlos syndrome diagnosed in the UK?
Diagnosis typically begins with a clinical evaluation by a specialist, often a clinical geneticist, based on symptoms. Confirmation usually involves genetic testing for pathogenic variants in the COL5A1 and COL5A2 genes. This testing is available through the NHS Genomic Medicine Service following specialist referral.
References
- Adam MP, Bick S, Mirzaa GM. Classic Ehlers-Danlos Syndrome. 1993. PMID: 20301422
- Chiu WC, Chen SH, Lo MC. Classic Ehlers-Dalnos syndrome presenting as atypical chronic haematoma: a case report with novel frameshift mutation in COL5A1. BMC pediatrics. 2020. PMID: 33109150