What is Ehlers-Danlos syndrome type IV and its common clinical manifestations?

Ehlers-Danlos Syndrome Type IV: Clinical Manifestations and Management

Ehlers-Danlos syndrome type IV (vascular EDS) is an autosomal dominant connective tissue disorder characterized by extreme tissue fragility that leads to life-threatening arterial, digestive, and uterine complications, with a median survival of only 48 years. 1, 2

Definition and Prevalence

• Vascular EDS represents approximately 5-10% of all EDS cases 2
• Overall EDS prevalence is estimated between 1/10,000 and 1/25,000 2
• Caused by mutations in the COL3A1 gene coding for type III procollagen 2
• Transmitted as an autosomal dominant trait 3, 2

Key Clinical Manifestations

Characteristic Physical Features

• Acrogeria (aged appearance of extremities) in most patients 2
• Translucent skin with highly visible subcutaneous vessels, particularly on trunk and lower back 1, 2
• Soft or velvety skin texture 1
• Tissue fragility and poor wound healing 1
• Atrophic scarring 1
• Easy bruising 1, 2

Vascular Complications

• Arterial dissection and rupture affecting large and medium-diameter vessels 2
• Dissections of vertebral and carotid arteries (including carotid-cavernous fistulae) 2
• Aortic dissection can occur without prior dilatation 3
• Coronary artery dissection (can lead to myocardial infarction) 4, 5

Gastrointestinal Complications

• High risk of recurrent colonic perforations 2
• Spontaneous liver rupture (rare) 6

Obstetric Complications

• Uterine rupture during pregnancy or labor 3, 2, 7
• Pregnancy significantly increases risk of vascular rupture 3, 2
• Maternal mortality rate during pregnancy reported as 11.5-25% 5

Other Manifestations

• Joint hypermobility (can be assessed using the Beighton scale) 1
• Pneumothorax (rare) 6
• Renal infarction (rare) 6

Diagnostic Approach

• Clinical diagnosis based on characteristic physical features 1, 2
• Non-invasive vascular imaging is essential (invasive angiography is contraindicated) 1
• Genetic testing for mutations in the COL3A1 gene confirms diagnosis 1, 2
• Beighton scale assessment for joint hypermobility 1

Management Considerations

General Approach

• Early recognition of symptoms is crucial for appropriate management 1
• Multidisciplinary care is recommended 1
• Avoid invasive diagnostic procedures due to high risk of complications 1

Pregnancy Management

• Pregnancy is a contraindication in vascular EDS due to risk of uterine rupture 3
• Complete vascular imaging is essential before pregnancy 1
• Cesarean delivery is recommended for women with known vascular EDS 1, 7
• Avoid betamimetic tocolytics in patients with EDS and preterm labor 4

Surgical Considerations

• Conservative approach is generally recommended for vascular complications 2
• Surgery may be required for potentially fatal complications 2
• Surgical repair may be complicated by tissue fragility, hemorrhage, and poor wound healing 3

Medication

• Beta-blockers like celiprolol may be beneficial (though lacking FDA approval) 1

Complications and Prognosis

• Life-threatening arterial ruptures are common 1, 2
• Median survival is approximately 48 years 1
• Phenotypic expression is variable, making prompt diagnosis difficult 6
• Pregnancy significantly increases mortality risk 7, 5

Early diagnosis and appropriate management are essential to prevent life-threatening complications in patients with vascular EDS. The condition should be suspected in young individuals presenting with unusual vascular or organ ruptures.