Ehlers-Danlos syndrome (arthrochalasia)

Overview

Ehlers-Danlos syndrome (EDS) is a group of inherited conditions that affect connective tissue, which provides support to many parts of the body, including skin, joints, and blood vessels. Arthrochalasia type EDS (aEDS) is a particularly rare form, known for its severe joint hypermobility and frequent dislocations. Individuals with aEDS typically have very flexible joints, which can lead to problems from an early age [PMID:32060934]. The condition is present from birth and can vary in how it affects each person, though significant joint involvement is a hallmark feature. Understanding aEDS is important for early diagnosis and appropriate management to improve quality of life.

Connective tissue is the 'glue' and scaffolding of the body, made up of proteins such as collagen. In aEDS, there is a problem with the production of type I collagen, which is a major component of skin, bones, tendons, and cartilage. This structural issue results in tissues that are weaker and less able to provide normal support, leading to the characteristic features of the syndrome. While aEDS is rare, it falls under the broader umbrella of EDS, which collectively affect around 1 in 5,000 people. However, the arthrochalasia type itself is much less common, with only a small number of cases reported worldwide.

Symptoms & clinical features

The primary clinical features of Ehlers-Danlos syndrome, arthrochalasia type (aEDS) are severe generalised joint hypermobility and congenital hip dislocation [PMID:32060934]. This means that many joints in the body can extend beyond their normal range of motion, often leading to instability and dislocations. Hip dislocations are particularly common and may be present at birth in both hips. Other joints, such as those in the knees, elbows, shoulders, and fingers, can also be affected, leading to frequent subluxations (partial dislocations) or full dislocations that can be painful and impact daily activities.

In addition to joint issues, individuals with aEDS often have skin involvement. The skin typically feels soft, velvety, and may be hyperextensible, meaning it can be stretched more than usual before returning to its normal position. However, it is not as fragile as in some other types of EDS. Easy bruising is also a common finding, along with a tendency for atrophic scarring, where scars appear thin and sunken. Muscle weakness can also be a feature, potentially contributing to joint instability and affecting motor development in children. The combination of these symptoms can lead to chronic pain and challenges with mobility, requiring ongoing medical and therapeutic support.

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Affected organs

Ehlers-Danlos syndrome, arthrochalasia type (aEDS) primarily affects organs and tissues rich in type I collagen. The most significantly impacted systems are the musculoskeletal system and the skin. In the musculoskeletal system, the joints are profoundly affected, leading to severe hypermobility and frequent dislocations, particularly of the hips, shoulders, and knees. This is due to the weakened connective tissue in ligaments and tendons that support the joints.

The skin is also consistently involved, exhibiting characteristic features such as softness, a velvety texture, and increased stretchiness. Easy bruising is common, and wounds may heal with thin, widened scars. While the major impact is on these systems, the widespread presence of type I collagen means that other connective tissues throughout the body can also be subtly affected. However, serious involvement of internal organs, such as the heart or blood vessels, is less typical compared to some other forms of Ehlers-Danlos syndrome.

Multiple body systems

Systemic involvement

Cellular impact

Mechanism at cellular level

Risks & severity

Ehlers-Danlos syndrome, arthrochalasia type (aEDS) is typically considered a severe form of EDS due to the significant joint involvement, particularly the congenital hip dislocations and frequent joint instabilities [PMID:20301490]. The severity of joint hypermobility and the frequency of dislocations can vary between individuals, but generally, these issues present significant challenges from infancy or early childhood. The need for surgical intervention for hip dislocations is common, often multiple times, and managing chronic joint pain and instability is a lifelong endeavour.

The lifetime risks associated with aEDS are mainly related to musculoskeletal complications. This includes chronic pain, early-onset osteoarthritis in frequently dislocated joints, and mobility limitations. There does not appear to be an increased risk of severe vascular complications or organ rupture as seen in some other EDS types. The condition is present from birth, and symptoms such as joint hypermobility and skin fragility are typically evident from infancy. The impact on an individual's quality of life often depends on the extent of joint involvement and the effectiveness of ongoing management strategies.

Genetic causes

Ehlers-Danlos syndrome, arthrochalasia type (aEDS) is caused by pathogenic variants in either the COL1A1 or COL1A2 genes. These genes provide instructions for making components of type I collagen, which is the most abundant type of collagen in the human body. Type I collagen is crucial for the strength and structure of connective tissues found in bones, skin, tendons, ligaments, and other fibrous tissues.

Pathogenic variants in COL1A1 or COL1A2 typically lead to a situation where parts of the collagen chains are not correctly processed. Specifically, it often involves a defect in the removal of the N-terminal propeptide, a small section that is usually trimmed off during collagen maturation [PMID:20301490]. When this trimming does not happen properly, the resulting collagen molecules cannot assemble into the strong, organised fibrils needed for healthy connective tissue. This structural defect weakens the connective tissue throughout the body, leading to the characteristic joint hypermobility, skin fragility, and other features observed in aEDS [PMID:16035071].

• COL1A1
  collagen type I alpha 1 chain
  The COL1A1 gene provides instructions for producing a key component of type I collagen, a protein vital for strengthening various connective tissues throughout the body.
• COL1A2
  collagen type I alpha 2 chain
  The COL1A2 gene provides instructions for producing a component of type I collagen, a crucial structural protein found in bones, skin, and other connective tissues throughout the body.

Inheritance pattern

Ehlers-Danlos syndrome, arthrochalasia type (aEDS) is inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of the altered gene (either COL1A1 or COL1A2) from one parent to develop the condition. If a parent has aEDS, there is a 50% chance with each pregnancy that their child will also inherit the condition, regardless of the child's sex.

In some cases, a new pathogenic variant (known as a de novo variant) can occur in an individual without either parent being affected. This means the genetic change happens for the first time in that person. While the condition can be inherited from an affected parent, de novo variants are also a significant cause. Genetic counselling is recommended for individuals with aEDS and their families to understand the inheritance pattern and reproductive risks.

Diagnosis & testing

The diagnosis of Ehlers-Danlos syndrome, arthrochalasia type (aEDS) is primarily based on clinical findings and is confirmed by genetic testing. Clinical suspicion often arises from the presence of severe joint hypermobility, especially congenital bilateral hip dislocations, and characteristic skin features such as softness and hyperelasticity [PMID:32060934]. A medical geneticist or a clinician experienced in connective tissue disorders typically makes the initial assessment.

Confirmation of aEDS involves genetic testing to identify pathogenic variants in the COL1A1 or COL1A2 genes. This testing is generally carried out following a referral from a specialist, often via the NHS Genomic Medicine Service (GMS) pathways in the UK. The relevant R-codes for genetic testing would typically fall under broader Ehlers-Danlos syndrome panels. Genetic testing can help confirm the diagnosis, classify the specific type of EDS, and inform family planning. Genetic counsellors play a vital role in explaining the testing process, interpreting results, and discussing the implications for the patient and their family.

Management & lifestyle

The management of Ehlers-Danlos syndrome, arthrochalasia type (aEDS) is focused on addressing symptoms and preventing complications, as there is currently no cure for the underlying genetic cause. Management is typically multidisciplinary, involving orthopaedic surgeons, physiotherapists, occupational therapists, and pain management specialists. Given the severe joint hypermobility and frequent dislocations, orthopaedic care is paramount, often involving surgical correction for congenital hip dislocations and management of other unstable joints.

Physiotherapy and occupational therapy are crucial to help maintain muscle strength, improve joint stability, and teach strategies for protecting joints and performing daily activities safely. Pain management strategies are often necessary for chronic joint pain. Regular monitoring for complications and a tailored approach to care within the NHS framework, guided by a clinical geneticist, are essential. Genetic counsellors can also provide support and information. While specific drugs for aEDS are not available, symptomatic treatments and supportive therapies aim to improve mobility and quality of life.

UK care pathway

In the UK, individuals suspected of having Ehlers-Danlos syndrome, arthrochalasia type (aEDS) would typically be referred to a clinical genetics service or a specialist clinic for connective tissue disorders. These services operate within the NHS Genomic Medicine Service (GMS). Genetic testing for aEDS would be accessed through the GMS, falling under specific R-codes for inherited connective tissue disorders, allowing for identification of pathogenic variants in the COL1A1 or COL1A2 genes. A genetic counsellor will provide support throughout the diagnostic process, explaining the implications of the condition and inheritance patterns. Following diagnosis, care often involves a multidisciplinary team to manage the various symptoms, ensuring a comprehensive and coordinated approach.

Related conditions

Ehlers-Danlos syndrome (aEDS) shares features with other connective tissue disorders, particularly other types of Ehlers-Danlos syndrome and conditions involving collagen defects. For example, some forms of osteogenesis imperfecta (brittle bone disease) are also caused by pathogenic variants in COL1A1 or COL1A2, but typically lead to more severe bone fragility and fewer joint dislocations. Other EDS types, such as hypermobile EDS or classical EDS, also present with joint hypermobility and skin involvement, but usually without the congenital hip dislocations and specific molecular defect seen in aEDS. Differentiation relies on careful clinical assessment and genetic testing to pinpoint the exact genetic cause and guide appropriate management.

• Osteogenesis imperfecta (all types)
  Connective Tissue
  Shares 2 genes
• Otosclerosis
  Hearing Loss
  Shares 1 gene

Frequently asked questions