What is Ehlers-Danlos (EDS) syndrome?

What is Ehlers-Danlos Syndrome?

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders characterized by the defining triad of joint hypermobility with recurrent dislocations or subluxations, skin hyperextensibility, and tissue fragility. 1

Core Pathophysiology

• EDS comprises 13 recognized subtypes, with 12 being rare monogenic conditions caused by pathogenic variants in 19-21 different genes, mostly related to collagen synthesis and extracellular matrix organization 1, 2
• The connective tissue is softer and less rigid than normal due to disorganization of collagen and elastin fibers 3
• Many EDS types are metabolic diseases related to enzymatic defects affecting collagen formation and/or stability 4, 2

Epidemiology

• The hypermobile type (hEDS) is by far the most common, accounting for 80-90% of all EDS cases 3, 5
• Overall EDS occurs in approximately 1 in 5,000 births 6
• hEDS is more common than Marfan syndrome, which has a frequency of 2-3 cases per 10,000 population 3, 5

Clinical Hallmarks

The classic triad includes:

• Joint hypermobility with recurrent dislocations or subluxations 1
• Skin hyperextensibility (soft, velvety skin with normal or slightly increased extensibility) 1
• Tissue fragility resulting in easy bruising and abnormal scarring 7

Key Clinical Features by Type

Hypermobile Type (hEDS)

• Generalized joint hypermobility confirmed by Beighton scale: ≥6/9 points for prepubertal children, ≥5/9 for adults under 50, and ≥4/9 for adults over 50 1, 3
• Chronic joint or limb pain 1
• Asthenic syndrome and kyphotic spinal deformity (75% of cases) 3
• High palate and earlobe elasticity (63% of cases) 3
• Gastrointestinal symptoms (up to 60% of patients), with up to 98% meeting criteria for gut-brain interaction disorders 3, 5
• Aortic root dilation occurs in 25-33% of cases 1
• No identified genetic cause yet, unlike other EDS subtypes 5, 2

Vascular Type (Type IV)

• Poses the greatest risk due to danger of spontaneous arterial and organ ruptures 1, 5
• Transmitted as autosomal dominant 6
• Aortic dissection may occur without dilatation 6
• Affected individuals typically have short, slim build with prematurely aged hands, triangular faces, large eyes, small chins, thin pinched noses, and small lobeless ears 6

Critical Diagnostic Approach

Physical examination should focus on:

• Beighton scale assessment for joint hypermobility 1
• Skin texture evaluation (soft, velvety quality) 1
• Assessment of tissue fragility and bruising patterns 1

Essential workup includes:

• Echocardiogram to evaluate for aortic root dilation (present in 25-33% of hypermobile and classic types) 1
• Dilated eye exam to exclude Marfan syndrome 1
• Genetic testing is indicated if clinical features suggest a monogenic EDS type, but is unrewarding for hEDS 2

Important Clinical Pitfalls

• Determining the specific EDS subtype is crucial because different types have various clinical manifestations, genetic causes, and require individualized surveillance strategies 1
• Incisions heal slowly; retention sutures should be used and left in longer than normal with extended antibiotic coverage 6
• During pregnancy, women may show increased bruising, hernias, varicosities, or suffer rupture of large blood vessels, with severe postpartum hemorrhage risk 6
• Early diagnosis is critical to optimize symptomatic management and prevent avoidable complications, requiring multidisciplinary care in specialized centers 4