Faculty Collaboration Database

Marfan syndrome type II: there is more to Marfan syndrome than fibrillin 1. Congenit Heart Dis 2006 Sep;1(5):229-32

Date

04/02/2008

Pubmed ID

18377530

DOI

10.1111/j.1747-0803.2006.00040.x

Scopus ID

2-s2.0-33748532784 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Marfan syndrome is a well-described autosomal dominant syndrome with widely variable clinical manifestations. Cardiovascular complications include mitral valve prolapse with or without associated mitral valve insufficiency, aortic root dilatation, and most importantly the occasional development of aortic aneurysms or rupture. Given the inconsistent phenotype along with the potentially life-threatening implications, clinicians are increasingly turning to genetic testing for definitive diagnostic confirmation. It has been well established that mutations in the FBN1 gene encoding the structural protein Fibrillin 1 is the molecular etiology of Marfan syndrome. However, there are numerous patients who meet the Ghent clinical diagnostic criteria for Marfan syndrome who do not have identifiable FBN1 mutations. Recently, mutations in TGFBR1 and TGFBR2 (transforming growth factor beta receptors 1 and 2, respectively) have been shown to result in Loeys-Dietz syndrome, a connective tissue disorder with significant phenotypic overlap with Marfan syndrome. Individuals with this Marfanoid disorder lack the ocular findings of Marfan syndrome and often have dysmorphic features such as unusual facies, cleft palate, and contractures. In addition, Loeys-Dietz syndrome patients often present in childhood with significant cardiovascular problems. This article serves to report an illustrative case of Loeys-Dietz syndrome and reviews the phenotypic consequences of FBN1 and TGFBR1 and TGFBR2 gene mutations.

Author List

Zangwill SD, Brown MD, Bryke CR, Cava JR, Segura AD

Authors

Joseph R. Cava MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Annette D. Segura MD Adjunct Assistant Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aorta
Child
Codon, Nonsense
DNA Mutational Analysis
Dilatation, Pathologic
Extracellular Matrix Proteins
Female
Fibrillin-1
Fibrillins
Humans
Magnetic Resonance Imaging
Marfan Syndrome
Microfilament Proteins
Mutation
Phenotype
Receptors, Transforming Growth Factor beta