What are the signs and symptoms of Ehlers-Danlos Syndrome (EDS)?

Signs and Symptoms of Ehlers-Danlos Syndrome

The clinical hallmarks of Ehlers-Danlos syndrome are joint hypermobility with recurrent dislocations, skin hyperextensibility with soft or velvety texture, and tissue fragility with easy bruising. 1

Core Clinical Features (The Defining Triad)

Joint Manifestations

• Generalized joint hypermobility is the most prominent feature, confirmed by Beighton scale scoring with thresholds of ≥6/9 points for prepubertal children, ≥5/9 for adults under 50 years, and ≥4/9 for adults over 50 years 1
• The Beighton scale assesses: passive dorsiflexion of fifth fingers beyond 90°, passive thumb apposition to the flexor forearm surface, elbow hyperextension beyond 10°, knee hyperextension beyond 10°, and ability to place palms flat on floor with knees extended during forward bend 2
• Recurrent joint dislocations or subluxations occur frequently, affecting multiple joints 1, 2
• Chronic joint or limb pain is a persistent symptom in most patients 1, 2

Skin Manifestations

• Soft or velvety skin texture with normal or slightly increased extensibility is characteristic, particularly in hypermobile EDS 1, 2
• Skin hyperextensibility varies by subtype, with more pronounced stretching in classical types 3, 4
• Easy bruising occurs with minimal trauma 1, 2
• Atrophic scarring and abnormal wound healing with tissue paper-like scars may develop 4
• Thin, translucent skin with visible veins suggests vascular EDS, the most dangerous subtype 5

Tissue Fragility

• Tissue fragility manifests as poor wound healing and increased surgical complications 1, 3
• In vascular EDS specifically, there is extreme fragility leading to spontaneous arterial and organ ruptures 1

Cardiovascular Manifestations

• Aortic root dilation occurs in 25-33% of hypermobile and classic EDS cases 1, 5, 2
• Arterial aneurysms and dissections are life-threatening complications, particularly in vascular EDS (type IV) 1, 5
• Arterial tortuosity can be detected on vascular imaging 5

Gastrointestinal Symptoms

• Gastrointestinal manifestations affect up to 98% of hypermobile EDS patients 5, 2
• Common symptoms include nausea, abdominal pain, constipation, bloating, early satiety, and reflux 5
• Functional bowel disorders are frequent supportive features 2
• Gastritis and delayed gastric emptying occur commonly 2
• Pelvic floor dysfunction with incomplete evacuation is highly prevalent 5
• Organ perforation can occur in vascular EDS 1

Autonomic Dysfunction

• Postural orthostatic tachycardia syndrome (POTS) is a common comorbidity, characterized by heart rate increase ≥30 beats/min (≥40 beats/min in adolescents 12-19 years) within 10 minutes of standing without orthostatic hypotension 5, 2
• Neurally mediated hypotension may occur 2
• Orthostatic intolerance symptoms are frequent 5

Musculoskeletal Complications

• Severe scoliosis can develop in certain subtypes 4
• Musculoskeletal pain is chronic and widespread 4
• Joint instability leads to functional limitations 4

Other Systemic Manifestations

• Obstetric complications including uterine and arterial rupture risk, especially in vascular type 5
• Easy bleeding tendency due to vascular fragility 4
• Mast cell activation symptoms including episodic flushing, urticaria, wheezing, and multisystem symptoms may occur 5
• Chronic urinary retention can be present 2

Subtype-Specific Features

Vascular EDS (Type IV) - Most Dangerous

• Spontaneous arterial rupture with median survival of 48 years 5
• Organ perforation can occur without warning 1, 4
• Thin, translucent skin is characteristic 5

Hypermobile EDS - Most Common (80-90% of cases)

• Predominant joint hypermobility without significant skin fragility 1, 2
• Absence of skin/soft tissue fragility distinguishes it from other subtypes 2
• Visceral hypersensitivity rather than true dysmotility causes GI symptoms 2

Critical Clinical Pitfalls

• Failure to recognize vascular EDS carries significant mortality risk from arterial or organ rupture 5
• The specific mutation does not predict disease type, course, or severity, as almost every family has its own mutation 1
• Symptoms vary by age, gender, lifestyle, and expression domains of EDS genes during development 6
• 26.4% of clinically diagnosed hEDS cases had alternative genetic conditions requiring different management, emphasizing the need for genetic testing 2