26th February 2025

Marfan syndrome

Marfan syndrome is caused by a mutation in the Fibrillin-1 gene (FBN1) and is inherited in an autosomal dominant pattern, although 25% of patients have de novo mutations.

Diagnosis of Marfan’s is made using the Ghent criteria, the key components of which are aortic root dilatation, ectopia lentis and FBN1 gene mutation.

Clinical features of Marfan syndrome

Patients have characteristic musculoskeletal findings. Excess growth of the long bones results in greater height than expected for their genetic background and increased arm length and arm-span-to-height ratio. Chest wall deformity is often present, with pectus carinatum more common than excavatum. Arachnodactyly (long, slim fingers) is also seen. There may be a high-arched palate.

The aortic root is often involved in up to 50% of children and 80% of adults. This manifests as aortic root dilation, aortic regurgitation and aortic dissection, which is the most common cause of morbidity and mortality. Other cardiac features are mitral valve prolapse, tricuspid regurgitation and subsequent heart failure. They can have a high risk of pneumothorax due to emphysematous changes and lung bullae in the upper lobes.

Ectopia lentis is another common feature of Marfan’s and is classically an upward dislocation of the lens. Dural ectasia (enlargement of the spinal canal) in the lumbosacral spine is common.

Homocystinuria is a condition that mimics Marfan’s; however, it has some distinguishing features, and differentiating between the two is a common exam question. Homocystinuria is caused by mutations in multiple genes, such as CBS, which encodes the cystathionine beta-synthase enzyme. Homocystinuria causes marfanoid body habitus and also causes ectopia lentis; however, the lens usually dislocates downward. Intellectual disability is commonly present, and there is a high incidence of thrombotic events, neither of which are associated with Marfan’s.