Clinical meaning
Marfan syndrome results from mutations in the FBN1 gene encoding fibrillin-1, a glycoprotein essential for elastic fiber integrity. Defective fibrillin leads to dysregulated TGF-beta signaling, causing progressive aortic root dilation, mitral valve prolapse, and aortic dissection risk. The clinician must manage lifelong cardiovascular surveillance and determine timing for prophylactic surgery.
Diagnosis & workup
Diagnostics & workup: - Order echocardiogram with aortic root measurements annually - Order CT or MR aortic angiography for complete aortic assessment - Order genetic testing and family screening - Order ophthalmologic exam (slit-lamp for ectopia lentis) - Order revised Ghent criteria assessment - Order exercise stress test before activity clearance
Risk factors: - Confirmed FBN1 mutation - Aortic root z-score >3 - Progressive aortic dilation (>0.5 cm/year) - Family history of aortic events <50 years - Pregnancy planning in affected women - Competitive or isometric exercise participation