Ehlers–Danlos syndrome

Overview

Ehlers–Danlos syndrome (EDS) refers to a group of rare genetic connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. The connective tissue, which provides strength and flexibility to the skin, joints, blood vessels, and organs, is affected due to defects in collagen or collagen-processing enzymes. EDS can range in severity from mild to life-threatening, depending on the subtype. There are currently 13 recognized types of EDS, each with its own clinical features and genetic basis.

Causes

EDS is caused by mutations in genes responsible for producing or processing collagen, a major structural protein in the body. The specific gene affected varies depending on the subtype. For example:

• Classical EDS: Mutations in COL5A1 or COL5A2

• Vascular EDS: Mutations in COL3A1

• Kyphoscoliotic EDS: Mutations in PLOD1 or FKBP14

• Hypermobile EDS (hEDS): Cause remains unknown; no definitive gene identified yet

The inheritance patterns vary—most forms are autosomal dominant, meaning one mutated copy is sufficient to cause the condition, while some types (e.g., kyphoscoliotic EDS) are autosomal recessive.

Symptoms

Symptoms of EDS differ depending on the type and severity, but common features include:

• Joint hypermobility: Joints move beyond the normal range, often resulting in dislocations or chronic joint pain

• Skin hyperextensibility: Skin that stretches more than usual and returns to normal when released

• Skin fragility: Skin that bruises or tears easily and heals slowly, often with atrophic (sunken or thin) scars

• Chronic pain and fatigue

• Frequent joint sprains, subluxations, or dislocations

• Gastrointestinal issues: Such as reflux, constipation, or irritable bowel syndrome

• Autonomic dysfunction: Seen in some cases as postural orthostatic tachycardia syndrome (POTS)

More severe subtypes may present with:

• Vascular complications: Fragile blood vessels prone to rupture (in vascular EDS)

• Scoliosis and muscle weakness: Particularly in kyphoscoliotic EDS

• Organ or uterine rupture during pregnancy

Diagnosis

Diagnosis of EDS is based on a combination of clinical criteria, family history, and genetic testing. Diagnostic steps include:

• Clinical evaluation: Physical examination to assess joint flexibility (using the Beighton score), skin characteristics, and scar pattern

• Family history: Many types of EDS have a clear hereditary pattern

• Genetic testing: DNA analysis to identify mutations in collagen-related genes (available for most subtypes except hEDS)

• Imaging studies: May be used to detect internal complications like organ rupture or scoliosis

• Echocardiography: Particularly important for vascular EDS to evaluate arterial health

For hypermobile EDS, diagnosis is clinical as no specific genetic test currently exists.

Treatment

There is no cure for Ehlers–Danlos syndrome, so treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach is often necessary, including:

• Physical therapy: To strengthen muscles, stabilize joints, and reduce dislocations

• Pain management: Using medications, braces, and lifestyle modifications

• Skin care: To minimize trauma and improve wound healing

• Cardiovascular monitoring: Regular checkups for patients with vascular EDS

• Surgical intervention: Occasionally needed for joint stabilization or vascular repair, though healing may be slow

• Genetic counseling: For individuals and families to understand inheritance risks and reproductive options

Patients are also advised to avoid high-impact sports, contact activities, and any action that might cause joint or vascular strain.

Prognosis

The long-term outlook for individuals with EDS varies depending on the subtype and severity. Many people with mild forms, such as hEDS, can lead relatively normal lives with appropriate management. Others, particularly those with vascular EDS, face a higher risk of life-threatening complications such as arterial rupture and may have a reduced life expectancy. Early diagnosis, preventive care, and lifestyle adaptations are critical to improving quality of life and reducing risks associated with the syndrome.