Overview
Clinical Meaning
Marfan syndrome is an autosomal dominant heritable connective tissue disorder caused by a pathogenic variant in FBN1 , the gene encoding fibrillin 1.
Marfan syndrome is an autosomal dominant heritable connective-tissue disorder caused by a pathogenic variant in FBN1, the gene encoding fibrillin-1. Abnormal fibrillin microfibrils weaken connective tissue and dysregulate transforming growth factor beta signalling. In the cardiovascular system, this gradually weakens the aortic media. The characteristic lesion is enlargement of the aortic root, particularly the sinuses of Valsalva. The enlarged aorta may remain clinically silent while the wall becomes increasingly vulnerable to dissection or rupture. This is why a patient can look well, have no exercise intolerance, and still require lifelong imaging and medication. The central clinical problem is therefore an aortopathy, not a primary myocardial or conduction disorder. Aortic diameter, rate of enlargement, family history, pregnancy, and acute symptoms determine urgency.