%0 Journal Article
%T Novel SMAD3 Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm
%A Kristi K. Fitzgerald
%A Abdul Majeed Bhat
%A Katrina Conard
%A James Hyland
%A Christian Pizarro
%J Case Reports in Genetics
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/591516
%X 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. 1. Introduction Familial thoracic aortic aneurysm can be divided into syndromic and nonsyndromic forms. While abdominal aortic aneurysm generally occurs sporadically, thoracic aortic aneurysm and dissection (TAAD) is inherited in an autosomal dominant manner with decreased penetrance and variable expression [1]. 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-¦Â signaling pathway, or components of the contractile unit of smooth muscle cells. The genetic etiology of nonsyndromic causes of familial TAAD is largely unknown; however, several genes including, MYH11, ACTA2, and MYLK have been implicated [2¨C4]. The genetic cause of syndromic forms of TAAD include FBN1, the cause of Marfan syndrome, SLC2A10, the cause of arterial tortuosity syndrome, and TGF¦ÂR1, TGF¦ÂR2, and the recent identification of TGF¦Â2, all of which cause Loeys-Dietz syndrome [5¨C9]. 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]. 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 also been observed in patients with defects in SMAD3 [11]. SMAD3 encodes an intracellular member of the TGF-¦Â signaling pathway that activates or
%U http://www.hindawi.com/journals/crig/2014/591516/