In Ehlers-Danlos syndrome type IV (vascular type), which collagen type is defective, and what is the primary molecular defect?

Explanation

## Ehlers-Danlos Syndrome Type IV (Vascular EDS) ### Genetic Defect **Key Point:** EDS type IV is caused by mutations in the **COL3A1 gene**, which encodes the pro-α1(III) chain of type III collagen. This is the most severe and life-threatening form of EDS. ### Type III Collagen Characteristics | Feature | Details | |---------|----------| | **Primary location** | Blood vessels, hollow organs, skin | | **Structure** | Homotrimer of α1(III) chains | | **Function** | Provides elasticity and tensile strength | | **Percentage in skin** | ~80% of collagen in dermis | ### Molecular Defect Mechanisms 1. **Point mutations** in COL3A1 → abnormal pro-α1(III) chains 2. **Glycine substitutions** in the Gly-X-Y repeat → disruption of triple helix 3. **Splice site mutations** → shortened or absent collagen chains 4. **Result:** Defective type III collagen with impaired structural integrity ### Clinical Manifestations **High-Yield:** EDS type IV presents with: - **Vascular complications** (rupture of arteries, bowel perforation) — most life-threatening - Thin, translucent skin with visible veins - Joint hypermobility (mild compared to other types) - Easy bruising and poor wound healing - Characteristic facial features: thin nose, small chin **Clinical Pearl:** Patients with EDS type IV have a significantly shortened lifespan due to spontaneous arterial rupture and sudden death. Genetic counseling and family screening are essential. ### Comparison with Other EDS Types | EDS Type | Collagen Defect | Gene | Key Features | |----------|-----------------|------|---------------| | **I** | Type I (quantity/cross-linking) | COL1A1/COL1A2 | Severe, lethal in some | | **II** | Type I (quality) | COL1A1/COL1A2 | Moderate | | **III** | Type I (mild) | COL1A1/COL1A2 | Hypermobility | | **IV (Vascular)** | Type III | COL3A1 | Vascular rupture, most severe | | **V** | Type II | COL2A1 | Skeletal dysplasia | | **VI** | Lysyl hydroxylase deficiency | PLOD1 | Kyphoscoliosis | **Mnemonic:** **"Vascular EDS = Type III collagen"** — Remember: **V**ascular → **III** (Roman numeral 3)