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

Type Sclera Inheritance Often De Novo Features
1 Blue sclera AD Yes Mildest form; hearing deficit in 50%
2 Blue sclera AR Yes Lethal in perinatal period
3 White sclera AR Yes Progressive deformities; most severe survivable form
4 White sclera AD Yes Moderate severity; hearing normal
5–8 Variable Variable Yes None have collagen 1 mutation; similar phenotypes to Osteogenesis Imperfecta

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
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