Connective Tissue Disorders

Marfan’s Syndrome

Epidemiology

• 1 in 10,000 live births
• No gender predilection

Aetiology

• Autosomal Dominant
• 25% new mutations
• Problem with Fibrillin gene on chromosome 15q21

Clinical Signs

• Tall, spindly hands, joint hypermobility
• Wrist Sign (Walker’s test): Index and thumb overlap when encircling opposite wrist
• Thumb Sign (Steinberg test): If thumb adducted across palm, it comes out of closed fist
• Arm span: height ratio > 1.05

Diagnostic Criteria (GHENT system)

• One major criterion in two different organ systems & involvement of a third

Main Affected Body Areas

1. Orthopaedic
   • Joint hypermobility
   • Scoliosis
   • Dural ectasia
   • Protrusio acetabuli
   • Planovalgus feet
2. Cardiothoracic
   • Pectus Excavatum
   • Spontaneous Pneumothorax
   • Aortic Dissection
   • Aortic root dilatation
   • Mitral valve prolapse
3. Eyes
   • Superior lens dislocation
4. Abdomen
   • Stretch marks
   • Recurrent hernias

Management

• Referral for ECHO if not done already
• Genetic counselling
• Aggressive treatment of scoliosis
  • High incidence of curve progression
  • Pseudoarthrosis may occur with fusion
  • Complicated by dural ectasia
• Surgical closure of triradiate cartilage to halt protrusio
• Surgery for planovalgus feet

Ehlers-Danlos Syndrome

Aetiology

• Disorder causing:
  • Hypermobility of joints
  • Excessive skin laxity
• All types have mutation of one of the COL genes
• 50% involve COL5A1 or COL5A2 (classic type: Type 5 collagen – skin collagen)
• Vascular and Spinal Subtypes have slightly different mutations
• Classic form is Autosomal Dominant

Clinical Features

• Skin:
  • Fragile
  • Lax
  • Easily scarred
• Joint Hypermobility:
  • Recurrent dislocations, especially shoulder
• Severe kyphoscoliosis (spinal subtype):
  • Needs aggressive treatment and long fusion
  • Pseudoarthrosis more common
• Cardiac:
  • Aortic root dilatation (get ECHO if not done)

Osteogenesis Imperfecta

Aetiology

• Mutation of COL1A1 or COL1A2 gene (Collagen 1)
• Affects normal bone formation

Clinical Features

• Bone heals normally but is very brittle
• Multiple recurrent fractures
  • Olecranon apophyseal avulsion fracture is frequent
  • Fractures slow down after maturity
• Short stature
• Normal intelligence
• Scoliosis
• Basilar invagination
• Codfish vertebrae (multiple compression fractures)
• Tooth defects (dentinogenesis imperfecta)
• Hearing difficulty (deafness in 50% by age 40)
• Ligamentous laxity
• Increased risk of malignant hyperthermia

Subtypes

Management

Non-surgical

• Genetic counselling
• Bisphosphonates:
  • Shown to reduce fractures but complications if used long term
• Growth hormone
• Bone marrow transplant

Surgical

• Prophylactic or therapeutic fixation of fractures:
  • Use IM nails where possible to protect whole bone
• Treat scoliosis aggressively