PATHOLOGY & PATHOPHYSIOLOGY
What is the inheritance pattern of Marfan Syndrome?
Autosomal dominant
What three main body systems does Marfan Syndrome affect?
The cardiovascular, musculoskeletal, and ocular systems.
What is necessary for individuals with Marfan syndrome to have a normal life expectancy?
Early diagnosis + appropriate management
What diagnosis did we make via Katie’s CT? Be specific.
Descending OR Type B aortic dissection
What is the genetic basis of Marfan Syndrome?
Mutation in fibrillin-1 (FBN1) gene on chromosome 15
Name 2 ocular abnormalities associated with Marfan Syndrome.
Dislocated lens (—> lens subluxation), severe myopia, retinal detachment, glaucoma, early cataract formation.
What is the most common cause of death for individuals with Marfan syndrome?
Aortic dissection (or cardiac failure)
Name two symptoms of aortic dissection that Katie reported upon ED admission.
Severe chest pain & severe back pain
Name 2 effects of elevated TGF-ß. For an extra 100 pts…what causes elevated TGF-ß in individuals with Marfan Syndrome?
Dysregulated bone + cartilage growth; increased matrix metalloproteinase; increased collagen turnover; dysfunctional cell cycle regulation (proliferation, differentiation, apoptosis).
BONUS: Fibrillin-1 (FBN1) gene mutation decreases binding to TGF-ß, increasing unbound TGF-ß, and exerting aforementioned effects.
Name 3 cardiovascular abnormalities associated with Marfan Syndrome.
Aortic aneurysm, aortic root dilation, aortic regurgitation, aortic dissection, mitral valve prolapse, berry aneurism (—> subarachnoid hemorrhage)
Name at least 3 diagnostic methods for Marfan Syndrome.
Ghent criteria, genetic testing, echocardiogram, cardiac MRI/CTA, slit-lamp examination, skeletal X-ray or MRI
What was the indication of Katie’s “mid-systolic click heard best at apex”? Explain the physiological dysfunction responsible for this heart sound.
Mitral valve prolapse, is a cardiac condition that results in floppy mitral valve leaflets that bulge backward into the left atrium during contraction/systole.
Mitral valve regurgitation occurs when blood leaks back into the left atrium from the ventricle.
Explain how the MFS gene mutation affects cardiovascular health and functioning.
Elastin provides reversible stretch + strength to the arteries, reducing the workload of the heart by allowing them to expand and recoil as the heart pumps blood and preventing hypertension.
(FBN1 gene mutation —> defective fibrillin-1 —> defective microfibrils in connective tissue —> defective elastin)
Name 4 musculoskeletal abnormalities associated with Marfan Syndrome.
Tall stature with disproportionately long extremities, joint hypermobility, high-arched palate, arachnodactyly (abnormally long, slender fingers and toes), pectus carinatum OR pectus excavatum, spinal deformities (ex: scoliosis)
What drug two classes are typically used to treat hypertension in individuals with Marfan Syndrome? Describe their affects on the cardiovascular system.
Beta-blockers: decrease heart rate + blood pressure, decrease stress on aorta, decrease rate of aortic dilation
Angiotensin receptor blockers (ARBs): inhibit TGF-ß signaling, decrease aortic dilation
Why did we switch Katie from metoprolol to labetalol?
Reflex tachycardia is an adverse effect of nitroprusside, which Katie was taking with metoprolol. In patients with aortic dissection, we want to avoid tachycardia because it can worsen the dissection and/or lead to rupture.
Additionally:
Prior to starting labetalol, Katie was taking metoprolol + nitroprusside, two antihypertensive medications. Metoprolol is beta-1 selective, but labetalol targets both alpha- and beta-receptors.
By targeting multiple receptors, labetalol puts less overall stress on the heart.