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On a routine medical examination, a 19-year-old man is found to have a mid systolic click followed by a heart murmur. His height is 78 in, and weight is 157 lb. Physical examination shows arms that are disproportionately long compared with his trunk (arm span of 81 in), thumbs that can be extended to the wrist, pectus excavatum, and laxity of ligaments. Ocular examination demonstrates dislocation of one lens. Family history is positive for sudden death of his father at the age of 41 due to heart problems.


  • With an estimated prevalence of 1 in 3000 to1 in 5000 individuals, Marfan syndrome (MFS) represents the most common autosomal dominant multisystem disorder of the connective tissue with primary predilection of the skeletal, cardiovascular, and ocular system with consequent bone overgrowth, aortic root dilation, and/or aortic dissection and ectopia lentis, respectively.


  • The underlying pathophysiology responsible for the development and progression of MFS is the mutation of the fibrillin-1 (FBN1) gene located on chromosome 15q12. FBN1 regulates expression of the protein fibrillin-1 (composed of 2871 amino acids).1 There have been more than 1200 identified mutations that affect the FBN1 gene, the majority of which are missense mutations with high affinity for highly conserved cysteine residues. Other mutation types include nonsense small deletions and duplications, splice-site alterations, and mutations involving calcium-binding residues.

  • Fibrillin is the major protein component of the 10 nm microfibrils of the extracellular matrix that forms the scaffold for the deposition of elastin in tissues of the heart valves, aorta, lens suspensory ligaments, and other ligamentous structures.2 In addition, data from numer-ous genetic studies show that fibrillin has an important function in nonelastic tissues, such as ciliary zonules of the eye, tendons, and periosteum of the bone.


Clinical Features

  • The clinical features of MFS, including tall stature and slender digits, were first described by the French pediatrician Dr. Antoine Marfan in 1896 in a 5-year-old female patient. Today, initial diagnosis is usually made clinically utilizing the Ghent criteria, an international diagnostic algorithm based largely on clinical findings in the various earlier-mentioned organ systems, as well as on family history. Given that MFS demonstrates a wide phenotypic variety, in which mildly affected patients may be overlooked, the Ghent criteria underwent a revision in 2010 to decrease the risk of misdiagnosis3 (Table 37-1). The authors of the 2010 revision placed more emphasis on aortic root aneurysm and/or dissection and ectopia lentis and removed some of the less specific manifestations from the diagnostic algorithm. The Ghent criteria are best applied by a geneticist.

  • A high index of suspicion for MFS should be raised in patients with the presence of the following clinical features: characteristic tall and thin body habitus with long extremities, long ...

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