Clinical meaning
Defective fibrillin-1 impairs elastic fiber assembly in the aortic media, leading to cystic medial necrosis. The weakened aortic wall progressively dilates at the sinuses of Valsalva, creating an aneurysm prone to dissection. TGF-beta dysregulation from abnormal fibrillin accelerates smooth muscle apoptosis and extracellular matrix degradation.
Diagnosis & workup
Diagnostics & workup: - Order annual echocardiogram for aortic root measurement - Order CT or MR angiography for comprehensive aortic assessment - Order genetic testing for FBN1 mutation confirmation - Order ophthalmologic exam for lens subluxation - Order skeletal survey for systemic features - Calculate revised Ghent criteria score
Risk factors: - Aortic root diameter >5.0 cm - Rapid aortic growth (>0.5 cm/year) - Family history of aortic dissection - Pregnancy (increased aortic wall stress) - Uncontrolled hypertension - FBN1 mutations associated with severe phenotype