Marfan Syndrome

Marfan syndrome is an autosomal dominant connective-tissue disorder caused by a pathogenic variant in FBN1 on chromosome 15q21. The gene encodes fibrillin-1, a structural component of microfibrils. When this scaffold is abnormal, the aortic wall loses some of its mechanical support and TGF-beta signalling becomes dysregulated. The resulting medial degeneration explains why progressive enlargement of the aortic root, followed by dissection or rupture, is the major life-threatening complication. Myxomatous mitral-valve change and other connective-tissue manifestations arise from the same underlying defect. Penetrance is essentially complete, but expression varies widely within a family. About 75% of affected people have an affected parent and about 25% have a de novo variant. Each child of an affected person has a 50% chance of inheriting the condition. There is no sex or ethnic predilection, and prevalence is estimated at approximately 1 in 5,000 to 1 in 10,000 people. The recognisable phenotype combines disproportionate skeletal growth, ocular abnormalities, and cardiovascular disease. Tall stature or long fingers alone is not diagnostic. The finding that should change the clinician’s level of concern is a syndromic pattern accompanied...