Marfan syndrome
Marfan syndrome is an autosomal dominant connective tissue disorder from FBN1 (fibrillin-1) mutations, with skeletal, ocular, and cardiovascular features. The cardiovascular risk drives prognosis: aortic root dilation predisposing to dissection and rupture, managed with beta-blockers or ARBs, activity restriction, surveillance imaging, and prophylactic aortic surgery.
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What this article covers
- Overview
Definition: Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene encoding fibrillin-1, affecting the skeletal, ocular, and cardiovascular systems.
- Epidemiology
An uncommon inherited disorder, autosomal dominant with variable expression.
- Risk factors
FBN1 mutation and family history (autosomal dominant inheritance).
- Pathophysiology
Fibrillin-1 deficiency: abnormal microfibrils weaken connective tissue and dysregulate TGF-beta signaling.
- Clinical features
Skeletal: tall stature, long limbs, arachnodactyly, pectus deformity, scoliosis, and joint hypermobility.
- Differential diagnosis
Loeys-Dietz syndrome: aggressive aortopathy with arterial tortuosity, hypertelorism, and bifid uvula or cleft palate, distinguished from Marfan by TGFBR1/2 mutations and the absence of ectopia lentis.
- Diagnosis
Establish with the Ghent criteria integrating aortic root dilation, ectopia lentis, FBN1 mutation, and a systemic score: the diagnostic basis is the revised Ghent nosology, combining aortic root…
- Management
First-line, slow aortic growth and restrict high-risk activity: a beta-blocker (for example atenolol or metoprolol 50 to 100 mg PO daily) and/or an ARB (losartan 50 to 100 mg PO daily) to reduce…
- Complications
Aortic dissection and rupture (the leading cause of death).
- Prognosis
Markedly improved by surveillance, medical therapy, and prophylactic surgery, approaching near-normal life expectancy in treated patients.
- Prevention
Beta-blocker and/or ARB therapy to slow aortic dilation.
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