Marfan Syndrome

Marfan Syndrome: Pathogenesis and Clinical Findings
Inherited or acquired mutation in TGFBR1/2 gene (TGF-β receptor)
Dural ectasia
(widening of the dural sac)
Diminished and disorganized dural elastic fibres
Abnormalities in connective tissues
Tear in the aortic intima (innermost layer of aorta)
Aortic dissection
Type A (tear in ascending aorta) > Type B (tear in descending aorta)
Back pain
Sensory and motor deficits
Ectopia lentis
(lens dislocation)
Development of lung bullae and blebs
Rupture of bullae/blebs
** Abnormal properties of lens + cornea
** Scoliosis
** Myopia
Tall stature Chest wall (pectus)
Inherited (autosomal dominant) or de novo mutation in FBN1 gene
Distortion of neural roots
Thinning of ciliary zonules of the eye
Weakness and rupture of alveolar tissue
Production of aberrant or reduced fibrillin-1
Formation of unstable microfibrils in extracellular matrix of connective tissues
inactivate TGF-β1
↑ production of matrix metalloproteinases
↑ cellular signaling cascades
↑ production of growth factors in the endocardium
Cell proliferation and apoptosis suppression in mitral valve leaflets
Change in valvular architecture
Mitral prolapse
Mitral regurgitation
↑ degradation of extracellular matrix
Thinning of the aortic media
Weakness of the aortic wall
Inability of fibrillin- 1 to sequester and
↑ TGF-β1 signalling
• TGF-β: Transforming
growth factor beta (a cytokine)
**The underlying
mechanisms are unclear
Tony Gu Reviewers: Amanda Nguyen Davis Maclean Yan Yu* Michelle Keir*
* MD at time of publication
Aortic root dilation
Aortic valve leaflets stretched outwards, unable to fully close
Aortic regurgitation
Aneurysmal dilation of the abdominal & thoracic aorta
Aortic rupture
Blood enters and pressurizes a ‘false lumen’
Obstruction of aortic branches
End organ malperfusion
** deformities
** Joint hypermobility
Thumb sign: Thumb tip extends from palm of hand when thumb is folded into closed wrist
Wrist sign: thumb and fifth finger of the hand overlap when grasping opposite wrist
Sign/Symptom/Lab Finding
Published June 28, 2020 on