What are the clinical symptoms and management options for a patient with Ehlers-Danlos (EDS) syndrome?

Clinical Symptoms of Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome presents with a defining triad: joint hypermobility with recurrent dislocations or subluxations, skin hyperextensibility, and tissue fragility. 1

Core Musculoskeletal Features

Joint Hypermobility Assessment:

• Measure using the Beighton scale with age-specific thresholds: ≥6/9 points for prepubertal children, ≥5/9 for adults under 50 years, and ≥4/9 for adults over 50 years 1
• Recurrent joint dislocations and subluxations occur frequently 1
• Chronic joint and limb pain is a cardinal feature 1

Skin Manifestations:

• Soft, velvety skin texture with normal or slightly increased extensibility 1
• Skin hyperextensibility varies by subtype 2
• Easy bruising without significant trauma 1
• Abnormal wound healing with atrophic scarring 3
• Tissue fragility leading to skin tears 4
• In vascular EDS specifically, thin translucent skin with visible veins may be present 5

Cardiovascular Complications

Aortic Involvement:

• Aortic root dilation occurs in 25-33% of hypermobile and classic EDS cases 1, 5
• Vascular EDS (type IV) carries the highest mortality risk due to spontaneous arterial ruptures and organ perforations 1
• Arterial aneurysms and dissections can occur throughout the vascular tree 2

Gastrointestinal Symptoms

Highly Prevalent GI Manifestations:

• Up to 98% of hypermobile EDS patients experience gastrointestinal symptoms 5
• Common complaints include nausea, abdominal pain, constipation, bloating, early satiety, and reflux 5
• Pelvic floor dysfunction is highly prevalent 5
• Functional gastrointestinal disorders are frequently associated 6

Autonomic Dysfunction

Postural Orthostatic Tachycardia Syndrome (POTS):

• Heart rate increase ≥30 beats/min in adults (≥40 beats/min in adolescents 12-19 years) within 10 minutes of standing without orthostatic hypotension 5
• Orthostatic intolerance symptoms are common 6
• Chronic fatigue frequently accompanies autonomic dysfunction 6

Neuropsychiatric Features

• Anxiety disorders are commonly associated with hypermobile EDS 6
• Chronic pain syndromes beyond joint pain 6
• Generalized fatigue 6

Mast Cell Activation Syndrome

Associated MCAS Symptoms:

• Episodic multisystem symptoms involving ≥2 physiological systems 5
• Flushing, urticaria, wheezing 5
• Mechanical stimuli can trigger mast cell degranulation in hypermobile EDS patients 7
• Baseline serum tryptase may be elevated, with diagnostic increases of 20% above baseline plus 2 ng/mL during symptom flares 5

Subtype-Specific Features

Vascular EDS (Type IV) - Most Dangerous:

• Median survival 48 years due to arterial rupture risk 5
• Spontaneous arterial and organ ruptures 1
• Caused by COL3A1 gene mutations affecting type III collagen 1

Hypermobile EDS - Most Common:

• Accounts for 80-90% of all EDS cases 1
• No identified genetic markers; diagnosis is clinical 5
• Altered collagen fibril structure triggers fibroblast dysfunction 1

Classical EDS:

• Follows autosomal dominant inheritance 1
• Caused by COL5A1 or COL5A2 gene mutations 5

Additional Systemic Manifestations

• Pelvic and bladder dysfunction 6
• Severe scoliosis in some subtypes 3
• Obstetric complications including uterine and arterial rupture risk, especially in vascular type 5
• Easy bleeding tendency 3
• Delayed wound healing across all types 4, 2

Critical Pitfalls in Recognition

Do not miss vascular EDS, as it carries significant mortality risk from arterial or organ rupture and requires urgent genetic testing 5. Each family typically has its own specific mutation, and no genotype-phenotype correlations exist to predict disease severity 1. The hypermobile type has altered connective tissue with softer, less stiff properties that respond differently to mechanical stress 7.