Marfan’s Syndrome

  • First described by Marfan in 1896 in young patient with unusual skeletal deformities & generalised loss of musculature with no evidence of myopathy

Definition

  • Heterogeneous group of disorders
  • Inheritable generalized disorder of connective tissue
  • Common findings of
    • Skeletal changes
    • Lens dislocation
    • Cardiovascular disease

Epidemiology

  • 1:10 000 incidence
  • Males = Females
  • 75% AD
  • 25% new mutations (no family Hx)

Pathogenesis

  • Defect in cross-linkage of collagen with elastin
  • Abnormal fibrillar protein FBN1
    • Gene for fibrillin-1 (FBN1) located on long arm of chromosome 15 (15 q15-q21)
    • FBN1 is fibrillar protein found in aorta, eye & some CT
    • 30% have fibrillin-1 production reduced by half
    • 70% produce abnormal fibrillin-1 (abnormal allele)
  • Cross linkage of Collagen affected
    • Alpha-1 chain defect
  • Abnormal fibrillar protein weakens the Elastin fibrils

Diagnosis

  • Diagnosis made when patient meets at least 2 (preferably more) of the diagnostic criteria
    • Family history
    • Musculoskeletal abnormalities
    • Cardiac disease
    • Eye disease

Clinical Features

  • Phenotype variable
  • Not all have Marfanoid habitus
  • Major physical signs
    • Aortic dilatation
    • Ectopic lens 60% (superior dislocation)
    • Severe kyphoscoliosis
    • Chest wall deformity (Pectus excavatum > Carinatum)
  • Minor Physical signs
    • Generalised ligamentous laxity
    • Tall stature (>182cm) with slender limbs
    • Arachnodactyly
      • Subjective clinical impression
    • McKusick’s rule
      • Dolichostenomelia
      • Arm span three or more inches greater than height
      • (also seen in 60% normal males, 20% normal females)
    • Lawrence rule
      • Lower segment (pubis to heel) longer than upper segment
    • Knee sign
      • Legs crossed & the toe of top leg reaches the floor
    • Thumb sign (Steinbergs test)
      • Thumb held in clenched fist extends beyond the ulnar border of hand
    • Wrist sign (Bracelet sign)
      • Thumb overlaps the 5th finger when encircle the contralateral wrist
    • Mitral valve prolapse
    • Myopia
  • Findings by system include
  • Skeletal
    • Generalised ligamentous laxity
    • Instability/ subluxation or dislocation of
      • Patella
      • GHJ
      • SCJ
    • Spine
      • Scoliosis
      • Thoracic lordosis
      • Spondylolithesis or Spondyloptosis
    • Hip
      • Acetabular protrusio
      • Increased incidence of SUFE
    • Genu valgum/ recurvatum
    • Ankle instability
    • Pes planus
  • Ocular
    • Myopia
    • Superior lens dislocation (cf homocysteinuria)
  • Cardiovascular
    • Aortic dilatation/ dissection (cystic necrosis of the media with pools of mucoid material)
    • Aortic valve incompetance
    • Mitral valve incompetence
  • CNS
    • Dural Ectasia
    • Meningomyelocoele
  • Other
    • High arched palate
    • Hernias
  • Careful cardiac & opthamological follow-up required
  • 90% of affected individuals will die of cardiovascular complications

Investigations

Xray

  • Metacarpal Index
    • Length of MC 2-5 added / width of MC 2-5 added is > 8.5
  • 80% normal individuals between 5.4-7.0
  • 70% Marfan 8.4-10.4

Differential Diagnosis

  • Marfanoid habitus
    • Clinical & radiological measurements overlap the normal population
  • Ehlers-Danlos Syndrome
  • Homocysteinuria
  • Larsen’s Syndrome
  • Generalized ligamentous laxity
  • Congenital contractural arachnodactyly (CCA)

Orthopaedic Implications

  • Defective soft tissue
    • surgery aimed at soft tissue correction disappointing
  • Initial therapy aimed at improving muscle strength & relief of symptoms
  • Surgical intervention predominantly directed at kyphoscoliosis
  • Scoliosis
    • 40-60% of patients with Marfans
    • Only 20% of these require treatment
    • Similar to Idiopathic but usually develops early (< 9 years) & more progressive curves with poorer prognosis
    • Treatment plan as for idiopathic
    • Moe & Winter 1975
      • Sex incidence equal
      • Double right thoracic & left lumbar curves most common – different to idiopathic
      • More back pain on presentation
      • Younger onset than idiopathic
      • Use of Milwaukee brace limited
      • Pseudoarthrosis often complicates spinal fusion
      • Thorough cardiovascular evaluation required to exclude aneurysm or valvular lesions prior to surgery
  • Feet
    • Long narrow feet with disproportionately long great toe
      • May require custom shoes
    • Valgus hindfoot
      • Orthosis or arthrodesis

Future Directions

  • Genetic test for Marfan’s
  • Screening test to detect quantitative & qualitative deficiencies of fibrillin-1

Congenital Contractural Arachnodactyly

  • It is thought that CCA is the syndrome Marfan actually reported
  • However, CCA is mapped to a locus on chromosome 5
  • In addition to Trachnodactyly, Dolichostenomelia, & Scoliosis CCA demonstrates ear deformities