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Case Reports in Genetics
Volume 2014, Article ID 591516, 4 pages
Case Report

Novel SMAD3 Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm

1Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USA
2Department of Pathology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA
3Anatomy and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
4Connective Tissue Gene Tests, Allentown, PA 18106, USA

Received 14 November 2013; Accepted 6 January 2014; Published 3 March 2014

Academic Editors: C.-W. Cheng, M. Fenger, C.-S. Huang, P. Morrison, and G. Vogt

Copyright © 2014 Kristi K. Fitzgerald et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aneurysms-osteoarthritis syndrome (AOS) caused by haploinsufficiency of SMAD3 is a recently described cause of syndromic familial thoracic aortic aneurysm and dissection (TAAD). We identified a novel SMAD3 mutation in a patient with hypoplastic left heart syndrome (HLHS) who developed progressive aortic aneurysm requiring surgical replacement of the neoaortic root, ascending aorta, and proximal aortic arch. Family screening for the mutation revealed that his father, who has vascular and skeletal features of AOS, and his brother, who is asymptomatic, also have the pathogenic mutation. This is the first case report of a SMAD3 mutation in a patient with hypoplastic left heart syndrome. This case highlights the importance of genetic testing for known causes of aneurysm in patients with congenital heart disease who develop aneurysmal disease as it may significantly impact the management of those patients and their family members.