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Ehlers-Danlos syndrome

What's new

The American Gastroenterological Association (AGA) has issued a new clinical practice update on gastrointestinal manifestations and autonomic and immune dysfunction in hypermobile Ehlers-Danlos syndrome (hEDS). Evaluation for postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) is recommended in patients with suggestive clinical features, given the observed associations between hEDS and these conditions and their overlapping gastrointestinal manifestations. For POTS management, increased fluid and salt intake, exercise training, and the use of compression garments are suggested. Pharmacologic therapies targeting volume expansion, heart rate control, and vasoconstriction may be considered if symptoms persist despite lifestyle modifications. For MCAS, treatment with antihistamines and/or mast cell stabilizers, along with avoidance of known triggers, is recommended. Dietary modifications, including gastroparesis and various elimination diets, may also be beneficial for managing gastrointestinal symptoms. .

Background

Overview

Definition
EDS is a group of inherited connective tissue disorders characterized by hyperextensible skin, hypermobile joints, and tissue fragility.
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Pathophysiology
EDS results from defects in collagen synthesis or structure, leading to weakened connective tissues. Mutations in genes such as COL5A1, COL5A2, COL3A1, COL1A1, and COL1A2 are implicated in different subtypes, affecting the primary structure and later processing of type I, III, and V collagens.
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Epidemiology
The prevalence of EDS is believed to be underestimated, ranging from 1 in 5,000 to 1 in 400,000, depending on the subtype.
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Risk factors
Risk factors for EDS include a family history of the disorder, as it may be inherited in some cases depending on the subtype. It may also be associated with other genetic disorders or rheumatological diseases.
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Disease course
The syndrome is classified into several subtypes based on clinical presentation and genetic mutations, with the most common being the hypermobile, classical, and vascular types. Common features include joint hypermobility, skin hyperextensibility, easy bruising, and Marfanoid habitus. The vascular type is particularly severe, with risks of arterial rupture, organ rupture, and early mortality. Other complications can include chronic pain, joint dislocations, and early-onset osteoarthritis. Associated systemic findings include anxiety disorders, fatigue, orthostatic intolerance, functional gastrointestinal disorders, and pelvic and bladder dysfunction. In addition to the general features, specific subtypes may present with unique clinical manifestations. For instance, the hypermobility type caused by TNXB haploinsufficiency is associated with mild-to-moderate neuromuscular involvement, including muscle weakness, myalgia, and easy fatigability. The periodontal subtype, caused by mutations in C1R and C1S genes, is characterized by early severe periodontitis and gingival recession.
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Prognosis and risk of recurrence
The prognosis depends on the subtype and severity of the manifestations. While patients with the hypermobile and classical types may have a normal lifespan, vascular type is associated with an increased risk of life-threatening complications such as arterial rupture.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of Ehlers-Danlos syndrome are prepared by our editorial team based on guidelines from the American Gastroenterological Association (AGA 2025), the European Society for Vascular Surgery (ESVS 2024,2017), the European Society of Cardiology (ESC 2024,2018,2014), the American Heart Association (AHA/ACC 2022,2015), the American Academy of Family Physicians (AAFP 2021), and the Society ...
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Screening and diagnosis

Indications for screening: as per AGA 2025 guidelines, inquire about joint hypermobility in patients with disorders of gut-brain interaction and consider using the Beighton score as a screening tool. Consider using the 2017 diagnostic criteria to diagnose hypermobile EDS if the screen is positive.
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Beighton Score for Joint Hypermobility
Calculator
When to use
Age group
Prepubertal child
Adolescent or adult < 50 years
Adult ≥ 50 years
Passive dorsiflexion and hyperextension of the fifth metacarpophalangeal joint beyond 90 degrees
Neither fifth finger
Left fifth finger
Right fifth finger
Both fifth fingers
Passive apposition of the thumb to the flexor aspect of the forearm
Neither thumb
Left thumb
Right thumb
Both thumbs
Passive hyperextension of the elbow beyond 10 degrees
Neither elbow
Left elbow
Right elbow
Both elbows
Passive hyperextension of the knee beyond 10 degrees
Neither knee
Left knee
Right knee
Both knees
Active forward flexion of the trunk with the knees fully extended so that the palms of the hands rest flat on the floor
No
Yes
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  • Screening of family relatives

Diagnostic investigations

History and physical examination
As per AAFP 2021 guidelines:
Suspect hypermobile EDS/hypermobility spectrum disorders in patients with joint hypermobility and associated symptoms, such as joint pain or dislocations and typical skin findings, arthralgias, recurrent hernias, marfanoid habitus, or family history of EDS.
B
Use the Beighton score and a validated five-part questionnaire for the assessment of joint hypermobility in patients with suspected hypermobile EDS/hypermobility spectrum disorders.
B
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  • Evaluation for gastrointestinal symptoms

  • Genetic testing

Medical management

General principles: as per ESVS 2024 guidelines, refer patients with an aortic disorder to a multidisciplinary aortic team at a highly specialized center.
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  • Celiprolol

  • Management of gastrointestinal symptoms

Surgical interventions

Aortic aneurysm repair
As per ESVS 2024 guidelines:
Perform open surgical repair as the first option in young patients with suspected connective tissue disorders and an AAA.
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Individualize the threshold diameter for repair in patients with AAAs with an underlying genetic cause, depending on the underlying genetics and anatomy.
B
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Specific circumstances

Pregnant patients, counseling: as per ACC/AHA 2022 guidelines, offer genetic counseling to patients with EDS contemplating pregnancy to discuss the heritable nature of the condition.
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  • Pregnant patients (management)

  • Athletes

Follow-up and surveillance

Imaging follow-up: as per ESC 2024 guidelines, obtain regular vascular surveillance of the aorta and peripheral arteries by duplex ultrasound, cardiovascular CT, or cardiovascular MRI in patients with vascular EDS.
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