All material is copyrighted and the property of mehlmanmedical.
Copyright © 2020 mehlmanmedical.
Privacy Policy and Terms and Conditions
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 |
—
