What are the symptoms in the clinical presentation of Ehlers-Danlos syndrome (EDS)?

Clinical Presentation of Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome presents with a triad of joint hypermobility, skin abnormalities, and tissue fragility, but the specific symptom constellation varies dramatically by subtype, with hypermobile EDS (hEDS) being most common while vascular EDS carries life-threatening risks.

Core Musculoskeletal Manifestations

The hallmark feature across all EDS subtypes is generalized joint hypermobility, confirmed by Beighton score ≥5/9 in adults under 50 years, ≥4/9 for those over 50, and ≥6/9 for prepubertal children 1, 2. This manifests as:

• Recurrent joint dislocations and subluxations affecting multiple joints, particularly shoulders, patellae, and digits 2, 3
• Chronic musculoskeletal pain that is early in onset, severe, and debilitating—more prevalent and severe in hypermobile type than classic type 4
• Pain severity correlates directly with degree of hypermobility, number of dislocations, and previous surgical interventions 4
• Easy bruising without significant trauma 2, 3

Dermatologic Features

Skin manifestations are critical diagnostic clues 3, 5:

• Skin hyperextensibility—soft, velvety, or hyperelastic skin that can be stretched beyond normal limits 2, 3
• Atrophic scarring with poor wound healing 3
• Thin, translucent skin with visible veins (particularly in vascular EDS) 1
• Tissue fragility leading to easy tearing 3, 5

Cardiovascular Complications

Cardiovascular involvement varies by subtype but includes 1, 2:

• Aortic root dilation occurring in 25-33% of hypermobile and classic EDS cases 1, 2
• Arterial rupture, dissection, and aneurysm formation (primarily vascular EDS type IV) 6
• Palpitations and tremulousness 2
• Vascular fragility with risk of spontaneous arterial tearing in patients under 45 years 6

Critical pitfall: Vascular EDS (type IV) is life-threatening with median survival of 48 years due to arterial rupture risk—this subtype requires urgent COL3A1 genetic testing and avoidance of invasive vascular procedures 1, 6.

Gastrointestinal Symptoms

GI manifestations affect up to 98% of hEDS patients 7, 2:

• Nausea and abdominal pain predictive of abnormal GI motility 2
• Severe constipation, bloating, diarrhea, and vomiting 2
• Early satiety suggesting delayed gastric emptying 7, 2
• Gastroesophageal reflux and gastritis 2
• Colonic perforation and visceral rupture (vascular EDS) 6

Autonomic Dysfunction (POTS)

Approximately 37.5% of hEDS patients have POTS 7, 8, presenting with:

• Orthostatic intolerance with heart rate increase ≥30 beats/min in adults (≥40 beats/min in adolescents 12-19 years) within 10 minutes of standing without orthostatic hypotension 7, 1, 2
• Lightheadedness and generalized weakness upon standing 2
• Blurred vision with postural changes 2
• Cognitive dysfunction ("brain fog") 2
• Bladder dysfunction 2

The vascular laxity in hEDS predisposes to POTS through impaired venous return and peripheral pooling 8.

Mast Cell Activation Syndrome (MCAS)

MCAS occurs in a subset of hEDS patients 7, characterized by:

• Flushing and urticaria 2
• Wheezing and respiratory symptoms 8, 2
• Multisystem symptoms triggered by foods, alcohol, strong smells, temperature changes, and specific medications 2
• Symptoms typically occur in 2 or more body systems simultaneously 7

Important caveat: Up to 40% of patients report a viral infection as the precipitating event for symptom onset 2.

Respiratory Manifestations

Respiratory symptoms in hEDS result from 8:

• Inspiratory muscle weakness leading to blunted tidal volume expansion during exercise 8
• Connective tissue abnormalities compromising structural integrity of respiratory muscles and fascial attachments 8
• Dysfunctional breathing patterns with increased respiratory frequency and reduced tidal volume 8
• Bronchospasm from MCAS-related histamine release 8

Obstetric and Gynecologic Complications

Women with EDS face significant pregnancy risks 1:

• Uterine rupture risk (especially vascular type)
• Arterial rupture during pregnancy or delivery
• Pregnant women with vascular EDS require high-risk obstetric care 6

Subtype-Specific Presentations

Hypermobile EDS (80-90% of cases): Predominant joint hypermobility, chronic pain, GI symptoms, POTS, and MCAS associations 1, 2.

Vascular EDS (Type IV): Thin translucent skin, arterial/organ rupture, colonic perforation—presents with life-threatening complications in patients under 45 years 1, 6.

Classic EDS (Types I and II): Prominent skin hyperextensibility, atrophic scarring, joint hypermobility 1.

Critical diagnostic consideration: The clinical presentation may overlap with multiple conditions, and up to 26.4% of patients meeting hEDS criteria have an alternative or additional genetic diagnosis requiring distinct management 9. This underscores the importance of excluding alternative diagnoses through appropriate genetic testing when clinically indicated 1, 9.