Marfan Syndrome Flashcards
a mutation in FBN1 gene in the long arm of chromosome 15 affecting CT
marfan syndrome (autosomal dominant disorder)
responsible for encoding Fibrillin-1 glycoprotein
FBN-1 gene
importance of Fibrillin-1 glycoprotein
a major component of microfibrils found in ECM
roles of microfibrils
play a role in elastic fiber formation that allows skin, ligaments, & BVs to stretch
provides scaffolding framework into which tropoelastin gets deposited to make elastic fibers
MFS mainly affects what systems in the body?
cardiovascular (heart, BVs), skeletal, and ocular
Why is MFS mainly affecting the skeletal, CV, and ocular systems?
affected microfibrils are particularly abundant in the aorta, ligaments, and ciliary zonules, which suspend the lense of our eyes.
what are the 2 mechanisms that lead to MFS?
- loss of structural support in microfibril-rich CT
2. excessive activation of the important cytokine – Transforming GF-B
how does missense mutation contribute to MFS?
it results in development of abnormal fibrillin-1 glycoprotein, which inhibits polymerization. This decreases fibrillin, which then leads to weakening of elastic fibers.
why does the loss of structural support in microfibril-rich CT happen in MFS?
due to loss of microfibrils.
Normally, microfibrils sequester transforming GF-B, which enables them to control the bioavailability of the cytokine.
absence or lack of microfibrils allows these cytokines to accumulate, which has a damaging effect on smooth muscle cells of BVs. This also leads to the activation of METALLOPROTEASE (an enzyme responsible for destruction of ECM.)
(an enzyme responsible for destruction of ECM
metalloprotease
excessive activation of TGF-B
responsible for BONE OVERGROWTH and MYXOID CHANGES in mitral valve
what are myxoid changes?
- mitral valve prolapse
- thickening of valve leaflets and fibrosis
MFS ocular problem
- ectopia lentis (bilateral subluxation/dislocation of lens)
dislocation is upwards and outwards
MFS CV problems
- mitral valve prolapse, aortic aneurysm (aortic dilation, dissection)
in MFS, dilation of ascending aorta or aortic aneurysm is due to _______.
cystic medial necrosis or cystic medial degeneration
causes of mitral valve prolapse
- elongation of chordae tendineae
- elongation of valve ring
- redundant valve tissues
clinical features of MFS
- arachnodactyly
- arm span greater than height
- decreased ratio b/w upper and lower segments (torso is abnormally shorter compared to legs)
- hypermobile joints due to weakness of CT
- thumb can be hyperextended back to wrist
- prominent supraorbital ridges
- bossing on frontal eminence (protruding forehead)
- kyphosis, scoliosis
- pectus excavatum (pt at risk for pneumothorax)
- ectopic lentis
- floppy valve syndrome/mitral valve regurgitation
- aortic aneurysm/aortic dilation
what can pectus excavatum lead to?
decreased lung capacity –> restrictive pulmonary deficit (4-5%) –> spontaneous pneumothorax
why would patients with MFS also have sleep apnea?
due to laxity of pharyngeal tissues, blocking the airway
early diagnosis of MFS leads to ______
better prognosis
MFS and pregnancy
increased risk of aortic dissection
pt must be on frequent cardiovascular monitoring
what meds can we give pts w/ MFS?
beta blockers (decreases strain or aorta = slows rate of dilation) calcium channel blockers (if pt experiences sadness or nausea) losartan (blocks action of TGF-B)
When should we recommend aortic root surgery to patients w/ MFS?
- aortic root diameter greater than or equal to 50 mm
- rapide rate of enlargement (> 6-10 mm/yr)
- family hx of early aortic dissection
indications for preventive or prophylactic surgery
diameter of the aorta reaches 5 centimeters in older children or adults
rate of widening reaches 1 centimeter a year, or when there is severe or progressive backflow (regurgitation) of blood through the aortic valve
for leakage of the mitral valve
