Learning Objective: Identify the genetic, biochemical, and clinical features of Ehlers-Danlos Syndrome and differentiate between its major subtypes based on collagen defects and inheritance patterns.
Overview
Ehlers-Danlos Syndrome (EDS) refers to a group of inherited connective tissue disorders characterized by defective collagen synthesis, leading to hyperextensible skin, joint hypermobility, and tissue fragility.
Pathophysiology
EDS results from mutations in genes encoding collagen or enzymes involved in collagen processing.
- Collagen provides tensile strength to tissues like skin, ligaments, blood vessels, and organs.
- Defective collagen synthesis leads to weakened connective tissue → skin fragility, joint laxity, and vascular rupture.
Genetic Basis and Major Subtypes
| Type | Collagen Affected / Enzyme Defect | Key Features | Inheritance |
|---|---|---|---|
| Hypermobility Type | Unclear (most common form) | Joint hypermobility, recurrent dislocations, chronic joint pain | Autosomal dominant |
| Classical Type | Type V collagen (COL5A1, COL5A2) | Skin hyperextensibility, widened atrophic scars, joint hypermobility | Autosomal dominant |
| Vascular Type | Type III collagen (COL3A1) | Thin translucent skin, easy bruising, arterial/organ rupture (e.g., aortic or uterine rupture) | Autosomal dominant |
| Kyphoscoliotic Type | Lysyl hydroxylase deficiency | Congenital scoliosis, ocular fragility, severe muscle weakness | Autosomal recessive |
| Arthrochalasia Type | Procollagen peptidase deficiency | Severe joint hypermobility, recurrent subluxations, fragile skin | Autosomal dominant |
Key Clinical Clues
- Skin: Soft, hyperextensible, and fragile, with poor wound healing
- Joints: Hypermobile (“double-jointed”), frequent dislocations
- Vessels & Organs: Easy bruising, arterial aneurysms, and rupture risk
- Complications:
- Berry aneurysms → subarachnoid hemorrhage
- Aortic aneurysms/dissection
- Organ rupture, especially in the vascular subtype
Key Points
- Vascular EDS (Type III collagen defect) = life-threatening arterial rupture
- Classical EDS (Type V collagen) = skin + joint hypermobility
- Hypermobility type = most common; joint instability predominates
- Enzyme defect: Procollagen peptidase deficiency → failure of tropocollagen processing
