20. Marfan Syndrome

Question 1

what systems does Marfan Syndrome affect?

Answer 1

skel, cardiovascular, MSK, CNS, pulm

Question 2

dx of Marfan is based on what?

Answer 2

clinical phenotype

Question 3

Marfan’s is pleiotropic. what does that mean?

Answer 3

diverse/seemingly unrelated manifestations stem from a single mutation.

Question 4

why have the number of abnormalities seen in marfan’s increased?

Answer 4

better test methods, more clinicians looking, longer lifespans

Question 5

most obvious clinical manifestations of Marfan’s? and 3 cardinal features?

Answer 5

long arms, hands/fingers long, tall/thin patients, long narrow skull, deeply set eyes

1. family hx
2. ectopia lentis
3. aortic root dilation/aortic dissection

Question 6

cardiovascular manifestations of Marfan’s?

Answer 6

• mitral valve - looks like mitral valve prolapse. -aortic valve which is thin and myxomatous. -electrical disturbances.
• acute aortic dissection

Question 7

describe the mitral valve problems in Marfan’s?

Answer 7

often the earliest sign. reducdency of the valve leaflets, stretched chordae tendinae, dilation of the annulus. will progress to mitral valve prolapse.

Question 8

describe the aortic valve problems in Marfan’s?

Answer 8

aortic valve usually thin and myxomatous (weak connective tissue). occasional regurg.

Question 9

what is the major cause of sudden death with Marfan’s?

Answer 9

acute aortic dissection.

Question 10

three ways to treat Marfan’s?

Answer 10

1. restrict activity, reduce emotional stress
2. reduce stress in aortic wall: B blockers (propanolol, atenolol)
3. surgery with aortic root and valve replacement

Question 11

genetic cause of marfan?

Answer 11

disorder of connective tissue protein fibrillin.

Question 12

with Marfan, is there one mutation or many?

Answer 12

more than 60 distinct mutations of fibrillin that causes Marfan.

Question 13

what is dominant negative mutation?

Answer 13

even if a mutation only causes half of protein products to be defective, those products interact with the normal proteins in such a way that the normal ones are not able to function well. (here, combination of different fibrillin monomers -> defective multimers)

Question 14

is there genetic heterogeneity in Marfan? what about locus heterogeneity?

Answer 14

NO, everything is caused by one gene. however there are many mutations on that gene that cause Marfan (locus heterogeneity)

Question 15

Marfan: what is the penetrance?

Answer 15

about 70%. ie, only about 70% of individuals with the mutation will have the phenotype.

Question 16

what is the main thing that is affected with Marfan? ie, the one problem that makes all the other symptoms make sense?

Answer 16

problem with connective tissue/fibrillin gene.

Question 17

The gene FBN-1 encodes what protein?

Answer 17

Encodes a large glycoprotein, Fibrillin-1, involved in extra-cellular fibrillin integrity

Question 18

when would be the ideal time to do aortic repair on a Marfan’s pt?

Answer 18

before they dissect, but as late as possible. monitor aortic root dilation with ECHO.