Ehlers-Danlos Syndrome: Causes, Symptoms, and Diagnosis

Ehlers Danlos syndrome (EDS) is a group of hereditary connective tissue disorders which manifests clinically with skin hyperelasticity, hypermobility of joints, atrophic scarring, and fragility of blood vessels.

It is largely diagnosed clinically, although identification of the gene encoding the collagen or proteins interacting with it is necessary to identify the type of EDS. It is important to identify the type of EDS to guide management and counseling.

The prognosis depends on the type of EDS and the individual. Life expectancy can be shortened for those with the Vascular Ehlers-Danlos syndrome due to the possibility of organ and vessel rupture.

Ehlers-Danlos Syndrom


Life expectancy is usually not affected in the other types.

While there is no cure for the Ehlers-Danlos syndromes, there is treatment for symptoms, and there are preventative measures that are helpful for most.

Pathophysiology

The pathophysiology of most Ehlers Danlos syndrome subtypes involves heritable mutations in collagen synthesis and/or processing.

The inheritance pattern of these mutations is variable, including autosomal dominant and recessive inheritance involving different mutations; there are reports of spontaneous mutations causing identical genotypes and phenotypes.

The collagen affected by these mutations is integral to every body system, from the skin to the integrity of the vasculature, and as such, the symptoms of the disease can be variable and widespread.

Characteristics/Clinical Presentation

Patient presentations vary widely based on the respective underlying subtype. Ehlers-Danlos Syndrome contains at least six discernible phenotypes that are individually recognized.

Each type contains characteristics similar to the others. Each specific type presents with the same general clinical characteristics that are a result of faulty or reduced amounts of Type III collagen in the body: (Skin hyperextensibility and hyperflexible joints are two of the most common presenting signs of EDS).

Cutaneous manifestations are the hallmark of Ehlers-Danlos syndrome: include hyperextensibility, smooth and velvet-like texture, fragility, delayed wound healing, and thin atrophic scars after wound healing.

Common musculoskeletal manifestations include hypermobility leading to repeated subluxation and dislocation, which can lead to early osteoarthritis and chronic pain. This hypermobility may manifest as early as peripartum with hip dislocations in the newly delivered infant. Recurrent fractures may also be present.

Other tissues are subject to friability due to the underlying collagen dysfunction, including both hollow and solid internal organs. They can be subject to both spontaneous and traumatic rupture or perforation. Additionally, hernias and rectal prolapse are common features.

Classic facies include down slanting palpebral fissures, epicanthal folds, blue sclera, the appearance of premature aging, and micrognathia.

Neurological manifestations include hypotonia, which may manifest in the developing child as delayed motor milestones such as walking. Generalized pain, insomnia, and chronic fatigue are also prevalent.

Cardiovascular manifestations include mitral valve prolapse and, less commonly, tricuspid valve prolapse. Aortic root dilation is also a common feature that can lead to rupture without or without trauma.

Other vessels, such as intracranial arteries, may be aneurysmal, predisposing them to rupture. Capillary fragility may manifest as easy bruising and bleeding without underlying bleeding diathesis.

Chronic Pain may be present in patients with the Hypermobility Type of Ehlers-Danlos.

Diagnostic Criteria

Clinical Examination and a detailed family history have proven to be the most effective means of accurately diagnosing EDS.

Major diagnostic criteria typically includes:
  • Joint hypermobility as indicated by a score of greater than or equal to 6/9 on the Beighton scale (Gold standard)
  • Soft skin or skin hyperextensibility as defined by >1.5 cm on volar surface of forearm
  • Fragile skin or significant skin/soft tissue abnormalities (easy bruising, delayed wound healing, atrophic scarring, easy tendon, ligament, vessel rupture)

Systemic Involvement

Musculoskeletal
  • Joint laxity manifesting as recurrent joint subluxations/dislocations due to minimal trauma and/or spontaneous onset.
  • Osteoarthritis resulting in early onset of degenerative joint disease.
  • Osteoporosis due to reduction in general bone bone density up to 0.9 standard deviations lowering than the average, healthy adult
  • Scoliosis, Kyphosis
  • Chronic joint, ligament, tendon, or muscle pain due to myofascial and/or neuropathic source
  • Headaches related to muscle tension in cervical spine and TMJ dysfunction
Neuromuscular
  • Low muscle tone (hypotonia)
  • Generalized muscle weakness
  • Decreased reflexes in the knee extensors and flexors seen in adolescents
Neurological
  • Fatigue, pain and anxiety are often due to exhaustion of the CNS's reserves
  • Migraines often disabling, Chronic pain
  • Hyperalgesia is commonly seen in children and adults with hypermobility EDS due their central nervous system being highly sensitized
Cardiopulmonary

Dysautonomia or Autonomic Dysfunction resulting in abnormal chest pain, palpitations at rest or with exertion, or abnormal blood pressure responses.

Aortic Root Dilation resulting in predisposition to arterial fragility or rupture. Mitral Valve Prolapse with increased risk of developing infective endocarditis

Gastrointestinal
  • Functional Bowel Disorders (gastritis, irritable bowel syndrome, gastroesophageal reflux) occur in up to 50% of individuals with EDS
  • High prevalence of GI reflux abdominal pain, constipation and diarrhea in adolescents with hypermobility EDS
  • Integumentary
  • Hyperextensibility of skin
  • Fragility of soft tissue resulting in increased likelihood of rupture or tearing of internal organs
Genitourinary
  • Uterine Fragility
  • Premature rupture of fetal membranes during pregnancy
  • Pelvic prolapse
Ehlers-Danlos Syndrom


Management

Any provider caring for a patient with Ehlers-Danlos syndrome should be aware of the multitude of complications of the disease and potential preventative measures.

Treatment and management of patients with EDS should use a multidisciplinary approach that focuses on the prevention of disease progression and subsequent complications as there is no cure for the disease.

Specialists generally manage specific care within the field of which the patient has concerning pathology. eg.the monitoring of cardiovascular concerns will be by a cardiologist; likewise, musculoskeletal pathology is monitored and treated by an orthopedist; geneticist or family medicine provider acts as the primary provider referring the patient to these specialists.

Treatment of EDS typically consists of management of specific signs and symptoms of the condition as well as lifestyle adjustments to prevent injury/complications. These include:

Surgical/Invasive Procedures

Surgical and/or other invasive procedures are not necessarily recommended in patients with EDS as a means of primary treatment due to the impaired wound healing, increased likelihood of scarring, and increased likelihood of blood vessel rupture associated with EDS.

However, certain subtypes of EDS, most notably the classic and vascular subtypes of EDS possess an increased predisposition to surgical complications compared to the others.

Physical Therapy Management

PT's "play an important role in management through exercise prescription and patient education for many of these conditions. Each physical therapy plan of care must be specially created for the patient depending upon the subtype of EDS and the signs and symptoms of that patient. 

In general, physical therapy intervention focuses on decreasing the patient’s disability from a multidirectional approach.

Exercise program consisting of aerobic conditioning combined with a low resistance, high repetition resistive training program to promote increased joint stability by increasing general resting muscle tone

Assistive devices to provide loading relief to lower extremity joints during ambulation and weight bearing activities

Bracing to promote increased joint stability and decrease likelihood of joint subluxation/dislocation

Pain management techniques to address soft tissue, myofascial, and chronic joint pain associated with EDS

Safe, effective, efficient transfers to avoid excessive weight bearing or loading of lower extremity joints.
  • Proprioceptive Exercises
  • Aerobic training

Differential Diagnosis

  • Marfans Syndrome
  • Loeys-Dietz Syndrome
  • Stickler Syndrome
  • Williams Syndrome
  • Aarskog-Scott Syndrome
  • Fragile X Syndrome

Dr Rohit Bhaskar, Physio
Dr Rohit Bhaskar, Physio Dr. Rohit Bhaskar, Physio is Founder of Bhaskar Health and Physiotherapy and is also a consulting physiotherapist. He completed his Graduation in Physiotherapy from Uttar Pradesh University of Medical Sciences. His clinical interests are in Chest Physiotherapy, stroke rehab, parkinson’s and head injury rehab. Bhaskar Health is dedicated to readers, doctors, physiotherapists, nurses, paramedics, pharmacists and other healthcare professionals. Bhaskar Health audience is the reason I feel so passionate about this project, so thanks for reading and sharing Bhaskar Health.

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