NovelSMAD3Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm

Kristi K Fitzgerald,Abdul Majeed Bhat,Christian Pizarro,James Hyland,Katrina Conard

doi:10.1155/2014/591516

Abstract

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.

Highlights

Familial thoracic aortic aneurysm can be divided into syndromic and nonsyndromic forms
In addition to aneurysm and dissection, early osteoarthritis, and other systemic findings, congenital heart disease including persistent ductus arteriosus, atrial septal defect, pulmonary valve stenosis, atrial fibrillation, and bicuspid aortic valve have been observed in patients with defects in SMAD3 [11]
We present a 14-year-old boy born with hypoplastic left heart syndrome (HLHS) who developed significant aneurysm of the neoaorta and proximal arch after completed, staged palliation and who was found to have a novel, pathogenic SMAD3 mutation

Summary

Introduction

Familial thoracic aortic aneurysm can be divided into syndromic and nonsyndromic forms. The genes causing syndromic and nonsyndromic forms of TAAD encode proteins that compose the structural components associated with connective tissue, key members of the TGF-β signaling pathway, or components of the contractile unit of smooth muscle cells. In 2011 SMAD3, was shown to cause a new syndromic form of thoracic aortic aneurysm and dissection. The features of this condition included early onset osteoarthritis in the majority of patients and the authors proposed the name aneurysms-osteoarthritis syndrome (AOS) [10]. Further testing in the family revealed additional at risk family members and who were offered appropriate cardiovascular and orthopedic screening

Case Presentation

Findings

Discussion