Genetics Q

[GFLIP]

10 yo girl is diagnosed w/ Marfan Syndrome, an AD condition. After a review of her pedigree, you find no previous family history of this disorder. Which of the following is the most likely explanation for this pattern?

A. Highly variable expression of the disease phenotype
B. Incomplete penetrance
C. Mitochondrial compensation in the mother
D. New mutation transmitted by one of the parents to the affected girl
E. Pleiotrophy

[GFLIP]

ans is................................................ ................................(d)

[Dr. X]

a very good q to demonstrate elimination process technique. i pretty much eliminated all of em except d.

since few of you out there might restrict marfan syndrome to genetics.. heres comes integration (emb. path. biochem. gen. mix):

For marfan syn, related gene causes a defect in -->
Whats the common congenital cardiac defect due to marfan -->

[mammypriya]

fibrillin
"congenital???"
downs synd or AAA
the congenital is throwing me off...ugh.
waht is it??:confused:

[Dr. X]

first - fibrillin is right.
second - its aortic insufficiency.

also, there is an imp. association btw Mitral valve prolpase and Marfan syndrome. M for M.

[MDiva]

That "congenital" is throwing me off, too. When you say "congenital cardiac defect" I immediately think of VSD, PDA, etc. I wouldn't have considered mitral valve prolapse as a congenital cardiac defect. Where you referring to something else, perhaps? Please clarify.

[Dr. X]

sure.. no prob. the answer to the above are: 1st - its fibrillin gene. 2nd - its aortic insufficiency. please refer to pg. 243 of FA 07. ;)

another congenital cardiac defect is MVP that is associated with marfan syndrome. MVP alone (not just with marfan syndrome) is the most common valvlar disease. It is often asymptomatic and associated with midsystolic click and is followed by late systolic murmur. remember, MVP itself is the most common cause of "heart murmur" (pg. 447, FA07) and not limited to marfan syndrome alone. I jus remembered the association btw MVP and marfan from schooling (PDI actually) so jus threw it in. I doubt that step1 would ask to pick btw aortic insufficiency and MVP as answer choices because both are inter-related. i also did a quick check on web and heres what i found from "pub-med":

AIMS: To investigate the natural history of mitral valve and aortic abnormalities in patients with Marfan syndrome during childhood and adolescence. METHODS: Fifty two patients with Marfan syndrome were followed for a mean of 7.9 years. Occurrence of adverse cardiovascular outcomes was measured clinically and by ultrasound examination. RESULTS: Mitral valve prolapse (MVP) was diagnosed in 46 patients at a mean age of 9.7 years, more than 80% of whom presented as "silent MVP". Mitral regurgitation (MR) occurred in 25 patients, aortic dilatation in 43, and aortic regurgitation (AR) in 13. Both MVP and aortic dilatation developed at a constant rate during the age period 5-20 years. In 23 patients MVP was diagnosed before aortic dilatation, in 18 the reverse occurred, and in 11 patients the two abnormalities were diagnosed simultaneously. During follow up, 21 patients showed progression of mitral valve dysfunction; progression of aortic abnormalities occurred in 13. Aortic surgery was performed in 10; two died of subsequent complications. Mitral valve surgery was performed in six. In sporadic female Marfan patients the age at initial diagnosis of MVP, MR, aortic dilatation, and AR was lowest, the grade of MR and AR most severe, the time lapse between the occurrence of MVP and subsequent MR as well as between dilatation and subsequent AR shortest, and the risk for cardiovascular associated morbidity and mortality highest. CONCLUSIONS: During childhood and adolescence in Marfan syndrome, mitral valve dysfunction as well as aortic abnormalities develop and progress gradually, often without symptoms, but may cause considerable morbidity and mortality by the end of the second decade, especially in female sporadic patients.

[Dr. X]

Heres another one..

dont really wanna make up a fancy q. stem so... you have a blind person in your clinic who is presented with lactic acidosis. Through genetic history, you find out that this trait is passed from maternal DNA to all children.

1) for ms1/ms2 students --> Dx - ?
2) for step1 takers --> whats the Mechanism behind the build up of lactic acidosis?
3) for gunners --> this gene defect affects which complexes? (hint: 2 of em')

[GFLIP]

so basically, connective tissue disorders like Marfans can cause valvular problems (aortic insufficiency and MVP).

cool. thanks for the clarifications...

[MDiva]

Heres another one..

dont really wanna make up a fancy q. stem so... you have a blind person in your clinic who is presented with lactic acidosis. Through genetic history, you find out that this trait is passed from maternal DNA to all children.

1) for ms1/ms2 students --> Dx - ?
2) for step1 takers --> whats the Mechanism behind the build up of lactic acidosis?
3) for gunners --> this gene defect affects which complexes? (hint: 2 of em')

Thank you for the elegant explanation on Marfan's and the MVP connection. I'll give your questions a go.

1) Leber's optic neuropathy
2) no ox-phos/anaerobic respiration is one way to get lactic acid, another is by blocking and/or defect in pyruvate carboxylase in gluconeogenesis
3) by complexes, I can guess you are talking about the PDC, but not sure which gene it is :confused:

[Dr. X]

1) LHON - good stuff MDiva
2) you're right with why lactic acidosis occur, but the q. i am going for is how is it related to LHON. hint: think mitochondrial DNA.
3) hint: im talking about ETC. now i feel like i gave it away.. yet still.