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Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders

Michael J Wright, MBChB, MSc
Heidi M Connolly, MD, FASE
Section Editor
Harry C Dietz, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


One of the most common inherited disorders of connective tissue, Marfan syndrome (MFS, MIM #154700) is an autosomal dominant condition with a reported incidence of 1 in 3000 to 5000 individuals [1,2]. There is a broad range of clinical severity associated with MFS and related disorders, ranging from isolated features of MFS to neonatal presentation of severe and rapidly progressive disease involving multiple organ systems [3]. Although many clinicians view the disorder in terms of classic ocular, cardiovascular, and musculoskeletal abnormalities (picture 1), manifestations also include involvement of the lung, skin, and central nervous system.

The genetics, pathogenesis, clinical manifestations, and diagnosis of MFS and related disorders will be reviewed here. The management of patients with MFS and related disorders and issues related to pregnancy are discussed separately. (See "Management of Marfan syndrome and related disorders" and "Pregnancy and Marfan syndrome".)


MFS is a highly variable systemic tissue disorder with clinical characteristics similar to a variety of other hereditary disorders from which it should be distinguished. MFS is almost exclusively inherited in an autosomal dominant manner, although rare case reports have described recessive fibrillin 1 gene (FBN1) mutations [4]. While most individuals with MFS have an affected parent, 25 percent or more of probands have MFS as the result of a de novo mutation.

Most patients with the typical Marfan phenotype harbor mutations involving the gene (FBN1) encoding the connective tissue protein fibrillin-1 [5-7]. However, FBN1 mutations also cause a wide range of milder phenotypes that often show at least some overlap with the classic Marfan phenotype. (See 'FBN1/2 phenotypes' below.)

In a minority of cases (less than 10 percent) with typical Marfan phenotype, no mutation in FBN1 is identified [3]. Studies have suggested that at least some of these cases are due to a complete allele deletion, more complex rearrangements, or alterations in regulatory sequences involving the FBN1 gene. In some of these individuals with atypical presentations reminiscent of MFS, an inactivating mutation in a gene encoding for transforming growth factor-beta receptor (TGFBR) may be responsible. (See 'TGFBR mutations' below.)

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Literature review current through: Sep 2017. | This topic last updated: Nov 02, 2016.
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