Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations12. Issue 1 (13th December 2012)

• Record Type: Journal Article
• Authors: Teekakirikul, Polakit; Milewicz, Dianna M.; Miller, David T.; Lacro, Ronald V.; Regalado, Ellen S.; Rosales, Ana Maria; Ryan, Daniel P.; Toler, Tomi L.; Lin, Angela E.
• Is Part Of: American journal of medical genetics. Volume 161:Issue 1(2013:Jan.)
• Page Start: 185
• Page End: 191
• Publication Date: 2012-12-13
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.35659
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Dilation or aneurysm of the ascending aorta can progress to acute aortic dissection (Thoracic Aortic Aneurysms and Aortic Dissections, TAAD). Mutations in genes encoding TGF‐β‐related proteins (<italic>TGFBR1</italic>, <italic>TGFBR2</italic>, <italic>FBN1</italic>, and <italic>SMAD3</italic>) cause syndromic and inherited TAAD. <italic>SMAD4</italic> mutations are associated with juvenile polyposis syndrome (JPS) and a combined JPS–hereditary hemorrhagic telangiectasia (HHT) known as JPS–HHT. A family with JPS–HHT was reported to have aortic root dilation and mitral valve abnormalities. We report on two patients with JPS–HHT with <italic>SMAD4</italic> mutations associated with thoracic aortic disease. The first patient, an 11‐year‐old boy without Marfan syndrome features, had JPS and an apparently de novo <italic>SMAD4</italic> mutation (c.1340_1367dup28). Echocardiography showed mild dilation of the aortic annulus and aortic root, and mild dilation of the sinotubular junction and ascending aorta. Computed tomography confirmed aortic dilation and showed small pulmonary arteriovenous malformations (PAVM). The second patient, a 34‐year‐old woman with colonic polyposis, HHT, and features of Marfan syndrome, had a <italic>SMAD4</italic> mutation (c.1245_1248delCAGA). Echocardiography showed mild aortic root dilation. She also had PAVM and hepatic focal nodular hyperplasia. Her family history was significant for polyposis, HHT, thoracic aortic aneurysm, and dissection and skeletal features of Marfan syndrome in her father. These two cases confirm the association of thoracic aortic disease with JPS–HHT resulting from <italic>SMAD4</italic> mutations. We propose that the thoracic aorta should be screened in patients with <italic>SMAD4</italic> mutations to prevent untimely death from dissection. This report also confirms that <italic>SMAD4</italic> mutations predispose to TAAD. © 2012 Wiley Periodicals, Inc.</p> </abstract>