Phenotypic Diversity of Marfan Syndrome

Abstract

Marfan syndrome (MFS) is a genetic disorder primarily impacting the cardiovascular system, eyes, and skeletal structure, with its root cause being mutations in the FBN1 gene. The condition is notably associated with risks such as aortic aneurysm and aortic dissection, which largely drive mortality among those affected. However, the clinical presentation of MFS varies widely, and the link between specific genetic mutations and clinical symptoms is not straightforward. Although genetic testing is invaluable for diagnosing MFS, its capacity to forecast manifestations and predict patient outcomes is still limited. Thus, unraveling the underlying factors and mechanisms contributing to this phenotypic variability is crucial. Doing so can enhance genetic analysis, improving the prediction of clinical outcomes, and facilitate better risk stratification. This review provides an overview of the phenotypic diversity in MFS and underlying factors and mechanisms contributing to the phenotypic variability.

Keywords: FBN1 gene; genetic epigenesis; genotype-phenotype; marfan syndrome; modifier gene; phenotypes.