Marfan syndrome

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Marfan syndrome genetics

  • Autosomal dominant; chromosome 15; FBN1 / FBN2 genes
  • FBN1 / FBN2 code for fibrillin, which is a glycoprotein that forms a sheath around elastin
  • Marfan syndrome is NOT a collagen disorder.
Elastin and fibrillin work together. Fibrillin is a glycoprotein that forms a sheath around elastin. In other words, it forms a scaffold in which elastin can be deposited.

Once again, Marfan syndrome is not a collagen disorder.

The USMLE really wants you to be able to contrast elastin from collagen. (My HY post on collagen synthesis is here.)

In contrast to collagen, elastin has:

  • ↑ hydrophobic amino acids (alanine, valine, glycine)
  • ↓ hydroxylation (only non-hydroxylated proline + lysine)
  • No glycosylation, triple α-helix, or -S–S-heavy terminal regions.
  • Extensive desmosine crosslinking
    • Tropoelastin is secreted into the extracellular matrix, where its lysine side-chains covalently interact to form desmosine crosslinks.
    • Extensive desmosine crosslinking is what enables elastin’s resilient bending/stretching properties.
    • The desmosine crosslinking is catalyzed by lysyl oxidase.
  • Once elastin is formed following desmosine crosslinking, it interacts with fibrillin.
  • Fibrillin is a glycoprotein that forms a sheath around elastin. It forms a scaffold in which elastin can be deposited. (Correct, I’m telling you that for the third time)

HY Marfan syndrome features

  • Tall and lanky, with arachnodactyly (long fingers); arm-span greater than height (>1.05x)
  • Chest wall abnormalities (i.e., pectus excavatum/carinatum) → ↑ risk for spontaneous pneumothorax
  • Scoliosis
  • Pes planus (flat feet)
  • Hyperextensible joints
  • Dural ectasia (lower back pain caused by ballooning of the dural sac around the spinal cord)
  • Lens dislocations (fibrillin is abundant in the zonules of Zinn [fibrous ring that stabilizes the lens])
  • Mitral valve prolapse, aortic regurgitation, aortic dissection
If you get a stethoscope question in someone with Marfan syndrome, before you freak out about thinking you’re not great at auscultating heart sounds, remember that you’re looking for either AR or MVP.

AR = Decrescendo holodiastolic (pan-diastolic) murmur at the 2nd intercostal space, right sternal border

MVP = Mid-systolic click at the 4th intercostal space, left mid-clavicular line

  • Patients with Marfan syndrome are very tall because bone elongation occurs 2° to unstable periosteum resulting in pathologic longitudinal growth.
  • Lens dislocations are due to defective microfibrils within the suspensory ligaments.
  • Aortic regurgitation and aortic dissections occur due to weakening of the tunica media (cystic medial necrosis).
  • The mitral valve prolapse pathophysiology is described as myxomatous degeneration of the mitral valve. This term refers to thickening and redundancy of the mitral valve leaflets.
Hyperextensible skin and Circle of Willis berry (saccular) aneurysms are seen in Ehlers-Danlos syndrome, not Marfan syndrome.

These two distinctions are really HY on the USMLE!

What the fuck does “Marfanoid” mean?

  • “Oid” means looks like but ain’t.
  • Fibrinoid means looks like fibrin, but it ain’t fibrin. (Seen in polyarteritis nodosa)
  • Plasmacytoid means looks like a plasma cell, but it ain’t a plasma cell. (Plasmacytoid cells are seen in Waldenstrom macroglobulinemia)
  • Marfanoid body habitus means the patient looks like he or she has Marfan syndrome but doesn’t.
Homocystinuria = school-age child with Marfanoid body habitus, Hx of thrombotic event, and often blurry vision or lens dislocation

MEN 2B = Marfanoid body habitus, pheochromocytoma, medullary thyroid carcinoma, mucosal neuromas

1. a) What is the inheritance pattern of Marfan syndrome?

b) Which chromosome number?

c) Which genes?

2. What do the FBN1 and FBN2 genes code for? And what is it?

3. Is Marfan syndrome a collagen disorder?

 
 

4. In contrast to collagen, elastin has: (Select all that apply)

 
 
 
 
 
 

5. Which of the following is/are characteristic of Marfan syndrome? (Select all that apply)

 
 
 
 
 
 
 
 
 
 

6. Name two HY Marfanoid syndromes on the USMLE. Describe them.